Treatment of gastrointestinal infections
2000; Elsevier BV; Volume: 118; Issue: 2 Linguagem: Inglês
10.1016/s0016-5085(00)70006-0
ISSN1528-0012
AutoresSubhas Banerjee, J. Thomas LaMont,
Tópico(s)Microscopic Colitis
ResumoOf all the treatment options available to gastroenterologists, therapies for enteric infections are the most complex because of the large number of antimicrobials, and the most changeable because of emerging infections and evolving drug resistance. This review covers all common gastrointestinal infections and most uncommon ones. For infections encountered only rarely in a typical clinical setting, we provide recommendations in tabular form. Insofar as possible, our recommendations are evidence-based and current up to December 1, 1999. We have also indicated any recommendations that are controversial or for which acceptable alternatives are available. Infective esophagitis usually occurs in immunocompromised patients, especially in those with impaired cell-mediated immunity. Neutropenic patients, pharmacologically immunosuppressed patients including those receiving chemotherapy and steroids, solid-organ and bone marrow transplant recipients, and patients with acquired immune deficiency syndrome (AIDS) are at increased risk of developing infective esophagitis. Presenting symptoms include odynophagia, dysphagia, heartburn, and chest pain. Risk factors for candidial esophagitis in immunocompetent patients include diabetes, alcoholism, age, and steroid and antibiotic use. The decision whether to use topical therapy, oral systemic therapy, or intravenous systemic therapy is based on the degree of immunocompromise (Table 1). In AIDS patients with acute esophageal symptoms, endoscopy may not be necessary to establish a diagnosis of candidial esophagitis. Rather, proceeding directly to empirical treatment with fluconazole appears to be safe and effective, with complete symptomatic response in 82% of patients within 1 week and savings per patient of approximately $700 related to endoscopy.1Wilcox CM Alexander LN Clark WS Thompson III., SE Fluconazole compared with endoscopy for human immunodeficiency virus-infected patients with esophageal symptoms.Gastroenterology. 1996; 110: 1803-1809Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Endoscopic evaluation is reserved for patients failing to respond to 1–2 weeks of empiric therapy.2Wilcox CM. Short report: time course of clinical response with fluconazole for Candida oesophagitis in patients with AIDS.Aliment Pharmacol Ther. 1994; 8: 347-350Crossref PubMed Google Scholar, 3Laine L Bonacini M. Esophageal disease in human immunodeficiency virus infection.Arch Intern Med. 1994; 154: 1577-1582Crossref PubMed Google ScholarTable 1Treatment of Infective EsophagitisInfectionTreatment of choiceAlternate treatmentProphylaxisCandida esophagitisNormal immune systemNystatin 1–3 million units po qidFluconazole 50 mg po every dayClotrimazole troches 10 mg 5 times a dayKetoconazole 200 mg po every dayImpaired lymphocyte functionFluconazole 100 mg po every dayKetoconazole 400 mg po every day with flucytosine 100 mg/kg po every day for fluconazole resistanceFor frequent symptomatic relapses only: fluconazole 50 mg po every day or ketoconazole 200 mg po every dayKetoconazole 200–800 mg po every dayItraconazole 100–200 mg po every dayAmphotericin B 0.3 mg/kg IV every dayGranulocytopeniaFluconazole 200 mg po every dayFluconazole 200 mg IV every dayKetoconazole 400–800 mg po every dayAmphotericin B 0.5 mg/kg IV every dayHerpes simplex esophagitisImmunocompetent hostNo specific treatment necessarySymptomatic treatment: analgesics, viscous lidocaine, antacidsImmunocompromised hostAcyclovir 5 mg/kg IV every 8 h for 7–10 daysFoscarnet 40–60 mg/kg IV every 8 h for 2–3 weeks for acyclovir resistanceAcyclovir 400 mg po bidCytomegalovirus esophagitisGancyclovir 5 mg/kg IV every 12 h for 21 daysFoscarnet 90 mg/kg every 12 h for gancyclovir resistanceGancyclovir 5 mg/kg IV every dayFoscarnet 90 mg/kg IV every 12 h for 21 daysFoscarnet 90–120 mg/kg IV every dayGancyclovir 1 g po tidpo, orally; qid, 4 times per day; IV, intravenously; bid, 2 times per day; tid, 3 times per day. Open table in a new tab po, orally; qid, 4 times per day; IV, intravenously; bid, 2 times per day; tid, 3 times per day. For patients with a normal immune system, nystatin suspension, 1–3 million units orally 4 times per day, or 10 mg clotrimazole orally 5 times per day are equally effective. Immunocompromised patients require systemic therapy. Fluconazole (100–200 mg orally daily) is considerably superior to ketoconazole (200–400 mg orally every day) for candidial esophagitis, achieving endoscopic cure in 91% of treated patients, compared with only 52% for ketoconazole.4Laine L Dretler RH Conteas CN Tuazon C Koster FM Sattler F Squires K Islam MZ. Fluconazole compared with ketoconazole for the treatment of Candida esophagitis in AIDS. A randomized trial.Ann Intern Med. 1992; 117: 655-660Crossref PubMed Google Scholar Fluconazole is also superior to itraconazole in the treatment of candidial esophagitis in patients with AIDS, achieving cure in 81% of patients after 2 weeks of treatment vs. 66% for itraconazole.5Barbaro G Barbarini G Calderon W Grisorio B Alcini P Di Lorenzo G. Fluconazole versus itraconazole for Candida esophagitis in acquired immunodeficiency syndrome.Gastroenterology. 1996; 111: 1169-1177Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Itraconazole administered along with flucytosine (100 mg/kg orally every day) achieves cure rates similar to fluconazole, and this combination may be useful for treating fluconazole-resistant candidial esophagitis.6Barbaro G Barbarini G Di Lorenzo G. Fluconazole vs itraconazole-flucytosine association in the treatment of esophageal candidiasis in AIDS patients. A double-blind, multicenter placebo-controlled study.Chest. 1996; 110: 1507-1514Crossref PubMed Google Scholar Other options for treating fluconazole-resistant Candida esophagitis include increasing the dose of the azole, or using an alternative azole. However, cross-resistance between azoles often exists. Parenteral amphotericin B, 0.3–0.5 mg · kg−1 · day−1, is also an alternative.7Brockmeyer NH Hantschke D Olbricht T Hengge UA Goos M. Comparative study of the therapy of Candida esophagitis in HIV-1-infected patients with fluconazole or amphotericin B and flucytosine.Mycoses. 1991; 34: 83-86PubMed Google Scholar, 8Lake DE Kunzweiler J Beer M Buell DN Islam MZ. Fluconazole versus amphotericin B in the treatment of esophageal candidiasis in cancer patients.Chemotherapy. 1996; 42: 308-314Crossref PubMed Google Scholar New antifungals being developed, including rilopirox and voriconazole, appear to be effective in vitro against fluconazole-resistant Candida species.9Nenoff P Taneva E Pfeil B Oswald U Haustein UF. In vitro activity of rilopirox against fluconazole-susceptible and fluconazole-resistant Candida isolates from patients with HIV infection.Mycoses. 1999; 42: 55-60Crossref PubMed Scopus (5) Google Scholar, 10Ghannoum MA Okogbule-Wonodi I Bhat N Sanati H. Antifungal activity of voriconazole (UK-109,496), fluconazole and amphotericin B against hematogenous Candida krusei infection in neutropenic guinea pig model.J Chemother. 1999; 11: 34-39Crossref PubMed Google Scholar Primary prophylaxis against Candida infection in highly susceptible hosts is not recommended. Long-term secondary prophylaxis with ketoconazole, 200 mg orally every day, or fluconazole, 50 mg orally every day, was found to be well tolerated and decreased the cumulative probability of relapse at 12 months to 38% compared with 84% in untreated patients.11Parente F Ardizzone S Cernuschi M Antinori S Esposito R Moroni M Lazzarin A Porro GB. Prevention of symptomatic recurrences of esophageal candidiasis in AIDS patients after the first episode: a prospective open study.Am J Gastroenterol. 1994; 89: 416-420PubMed Google Scholar However, response to treatment of reinfection was poorer in patients who had received prophylaxis, possibly because of development of resistant strains. Given the risk of emergence of resistant strains and the high cost of these drugs, secondary prophylaxis should be limited to patients with frequent symptomatic relapses. Immunologic treatments being investigated include vaccines and anti-Candida antibodies.12Cardenas-Freytag L Cheng E Mayeux P Domer JE Clements JD. Effectiveness of a vaccine composed of heat-killed Candida albicans and a novel mucosal adjuvant, LT(R192G), against systemic candidiasis.Infect Immun. 1999; 67: 826-833Crossref PubMed Google Scholar, 13Han Y Morrison RP Cutler JE. A vaccine and monoclonal antibodies that enhance mouse resistance to Candida albicans vaginal infection.Infect Immun. 1998; 66: 5771-5776Crossref PubMed Google Scholar, 14Tollemar J Gross N Dolgiras N Jarstrand C Ringden O Hammarstrom L. Fungal prophylaxis by reduction of fungal colonization by oral administration of bovine anti-Candida antibodies in bone marrow transplant recipients.Bone Marrow Transplant. 1999; 23: 283-290Crossref PubMed Google Scholar Esophageal resection combined with systemic antifungal therapy has occasionally been necessary in cases of severe invasive esophageal candidiasis with transmural necrosis and perforation.15Gaissert HA Breuer CK Weissburg A Mermel L. Surgical management of necrotizing Candida esophagitis.Ann Thorac Surg. 1999; 67: 231-233Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Herpes simplex virus (HSV)-induced esophagitis occasionally occurs in immunocompetent patients and requires only symptomatic treatment with analgesics, viscous lidocaine, and antacids, because the illness is self-limited and complete resolution of symptoms can be expected within 10–12 days.16Desigan G Schneider RP. Herpes simplex esophagitis in healthy adults.South Med J. 1985; 78: 1135-1137Crossref PubMed Google Scholar, 17Galbraith JC Shafran SD. Herpes simplex esophagitis in the immunocompetent patient: report of four cases and review.Clin Infect Dis. 1992; 14: 894-901Crossref PubMed Google Scholar, 18Shortsleeve MJ Levine MS. Herpes esophagitis in otherwise healthy patients: clinical and radiographic findings.Radiology. 1992; 182: 859-861PubMed Google Scholar, 19Kurahara K Aoyagi K Nakamura S Kuwano Y Yamamoto C Iida M Fujishima M. Treatment of herpes simplex esophagitis in an immunocompetent patient with intravenous acyclovir: a case report and review of the literature.Am J Gastroenterol. 1998; 93: 2239-2240PubMed Google Scholar Specific treatment with acyclovir may be considered in debilitated patients with particularly severe odynophagia,19Kurahara K Aoyagi K Nakamura S Kuwano Y Yamamoto C Iida M Fujishima M. Treatment of herpes simplex esophagitis in an immunocompetent patient with intravenous acyclovir: a case report and review of the literature.Am J Gastroenterol. 1998; 93: 2239-2240PubMed Google Scholar but should be started early in the illness to significantly shorten the course. Specific antiviral therapy is required in the immunocompromised host to avoid persistent infection. No prospective, controlled, randomized studies on HSV esophagitis exist, and treatment regimes have been derived from therapeutic trials for other HSV mucocutaneous infections. The largest retrospective study on the treatment of HSV esophagitis comprises only 20 AIDS patients; acyclovir therapy led to resolution in 16 patients, with a partial response in 3 patients, but 5 patients (15%) subsequently relapsed.20Genereau T Lortholary O Bouchaud O Lacassin F Vinceneux P De Truchis P Jaccard A Meynard JL Verdon R Sereni D Marche C Coulaud JP Guillevin L. Herpes simplex esophagitis in patients with AIDS: report of 34 cases.Clin Infect Dis. 1996; 22: 926-931Crossref PubMed Google Scholar In the severely symptomatic immunocompromised patient, acyclovir is recommended in a dose of 5 mg/kg intravenously every 8 hours for 7–10 days. Oral maintenance therapy with 400 mg acyclovir orally twice per day should probably be given to this group. Resistance to acyclovir, famcyclovir, and valacyclovir occurs in viral strains with mutations in the thymidine kinase gene, required for phosphorylation of the drug to its active form. Foscarnet inhibits viral DNA polymerase and does not require phosphorylation, and is therefore recommended for resistant strains. In a randomized trial comparing foscarnet with vidarabine in 14 AIDS patients with acyclovir-resistant HSV infections, foscarnet, but not vidarabine, was found effective in all patients.21Safrin S Crumpacker C Chatis P Davis R Hafner R Rush J Kessler HA Landry B Mills J. A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome.N Engl J Med. 1991; 325: 551-555Crossref PubMed Google Scholar For the treatment of acyclovir-resistant strains, foscarnet is given in a dose of 40–60 mg/kg intravenously 3 times per day for 2–3 weeks. The pharmacological properties and mechanisms of activity of antiviral drugs have been detailed in a recent excellent review by Balfour.22Balfour Jr., HH Antiviral drugs.N Engl J Med. 1999; 340: 1255-1268Crossref PubMed Scopus (186) Google Scholar Acyclovir has been shown to be highly effective for prophylaxis of oropharyngeal herpes simplex in randomized placebo-controlled studies in patients receiving chemotherapy,23Saral R Ambinder RF Burns WH Angelopulos CM Griffin DE Burke PJ Lietman PS. Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. A randomized, double-blind, placebo-controlled study.Ann Intern Med. 1983; 99: 773-776Crossref PubMed Google Scholar and is now routinely used in a dose of 400 mg orally twice per day in transplant recipients and in patients undergoing chemotherapy who test seropositive for HSV. Valacyclovir and famcyclovir are 2 new DNA polymerase inhibitors with greater oral bioavailability than acyclovir. They are no more effective than acyclovir for mucocutaneous herpes, and are considerably more expensive. Surgery is occasionally required for spontaneous esophageal perforations associated with HSV esophagitis.24Cronstedt JL Bouchama A Hainau B Halim M Khouqeer F al Darsouny T. Spontaneous esophageal perforation in herpes simplex esophagitis.Am J Gastroenterol. 1992; 87: 124-127PubMed Google Scholar Esophagitis is usually only one manifestation of systemic infection that occurs predominantly in the immunocompromised host. In an uncontrolled study in AIDS patients with cytomegalovirus (CMV) esophagitis, induction therapy with intravenous gancyclovir 10 mg · kg−1 · day−1 for 14 days resulted in a complete response in 49% and a partial response in 29% of treated patients. Seven nonresponders received foscarnet 60 mg/kg intravenously 3 times per day, with a clinical response in 5 of these patients.25Wilcox CM Straub RF Schwartz DA. Cytomegalovirus esophagitis in AIDS: a prospective evaluation of clinical response to ganciclovir therapy, relapse rate, and long-term outcome.Am J Med. 1995; 98: 169-176Abstract Full Text PDF PubMed Scopus (28) Google Scholar Similar results were noted in a recent randomized controlled study in 23 AIDS patients comparing foscarnet and gancyclovir for the treatment of CMV esophagitis. Marked endoscopic improvement was observed in 73% of patients receiving foscarnet compared with 70% of gancyclovir-treated patients, with disappearance of inclusion bodies on follow-up biopsy in 55% and 50% of patients, respectively.26Parente F Bianchi Porro G. Treatment of cytomegalovirus esophagitis in patients with acquired immune deficiency syndrome: a randomized controlled study of foscarnet versus ganciclovir.Am J Gastroenterol. 1998; 93: 317-322Crossref PubMed Scopus (10) Google Scholar The current recommendation for treatment of acute CMV esophagitis is either gancyclovir 5 mg/kg intravenously twice per day or foscarnet 90 mg/kg intravenously twice per day for 3 weeks. Relapse occurs in up to 39% of patients at a median of 4 months.25Wilcox CM Straub RF Schwartz DA. Cytomegalovirus esophagitis in AIDS: a prospective evaluation of clinical response to ganciclovir therapy, relapse rate, and long-term outcome.Am J Med. 1995; 98: 169-176Abstract Full Text PDF PubMed Scopus (28) Google Scholar No controlled data exist for maintenance therapy for relapsing CMV esophagitis. Repeat induction therapy may be followed by maintenance treatment with gancyclovir 5 mg/kg intravenously every day or foscarnet 90–120 mg/kg intravenously every day. Oral gancyclovir may also be considered for maintenance in a dose of 1000 mg orally 3 times per day.27Whitley RJ Jacobson MA Friedberg DN Holland GN Jabs DA Dieterich DT Hardy WD Polis MA Deutsch TA Feinberg J Spector SA Walmsley S Drew WL Powderly WG Griffiths PD Benson CA Kessler HA. Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel.Arch Intern Med. 1998; 158: 957-969Crossref PubMed Scopus (120) Google Scholar Primary prophylaxis with oral gancyclovir 1000 mg 3 times per day does not appear to be effective in preventing disease in human immunodeficiency virus (HIV) patients.28Brosgart CL Louis TA Hillman DW Craig CP Alston B Fisher E Abrams DI Luskin-Hawk RL Sampson JH Ward DJ Thompson MA Torres RA. A randomized, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected individuals.AIDS. 1998; 12: 269-277Crossref PubMed Scopus (50) Google Scholar However, prophylaxis appears to be effective in organ transplant recipients, particularly when either the donor or recipient is seropositive, especially in the high-risk donor seropositive/recipient seronegative (D+/R−) group and in patients receiving antilymphocyte therapy.29Brennan DC Garlock KA Singer GG Schnitzler MA Lippmann BJ Buller RS Gaudreault-Keener M Lowell JA Shenoy S Howard TK Storch GA. Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients.Transplantation. 1997; 64: 1843-1846Crossref PubMed Scopus (125) Google Scholar, 30Gane E Saliba F Valdecasas GJ O'Grady J Pescovitz MD Lyman S Robinson CA. 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A number of effective regimens are available for treatment of giardiasis, and cure rates of up to 95% can be expected for most patients after a single course of therapy. The treatment of choice is metronidazole 250 mg orally 3 times per day for 5 days.32Vesy CJ Peterson WL. Review article: the management of giardiasis.Aliment Pharmacol Ther. 1999; 13: 843-850Crossref PubMed Scopus (36) Google Scholar Chromosomally mediated resistance to metronidazole may be seen, resulting in decreased drug uptake by the Giardia strain, and in decreased reduction of metronidazole to its active metabolite within the parasite.33Smith NC Bryant C Boreham PF. Possible roles for pyruvate:ferredoxin oxidoreductase and thiol-dependent peroxidase and reductase activities in resistance to nitroheterocyclic drugs in Giardia intestinalis.Int J Parasitol. 1988; 18: 991-997Crossref PubMed Scopus (13) Google Scholar, 34Boreham PF Phillips RE Shepherd RW. 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Five v ten days therapy with furazolidone for giardiasis.Am J Dis Child. 1983; 137: 267-270PubMed Google Scholar Quinacrine (no longer available in the United States) is somewhat less effective than metronidazole and less well tolerated,38Kavousi S. Giardiasis in infancy and childhood: a prospective study of 160 cases with comparison of quinacrine (Atabrine) and metronidazole (Flagyl).Am J Trop Med Hyg. 1979; 28: 19-23PubMed Google Scholar but may be a useful alternative for metronidazole-resistant strains. It is used in a dose of 100 mg orally 3 times per day for 5 days. Albendazole is useful for metronidazole-resistant strains, and also in returning travelers with additional helminthic infections. At a dose of 400 mg daily for 5 days, it is as effective as metronidazole, with success rates of 95%, and may be better tolerated.39Hall A Nahar Q. 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The drug of choice is trimethoprim-sulfamethoxazole, which in a randomized, placebo-controlled, double-blinded study at a dose of 160 mg/800 mg orally twice per day for 7 days eradicated infection in 94% of patients, compared with 12% of patients receiving placebo.49Hoge CW Shlim DR Ghimire M Rabold JG Pandey P Walch A Rajah R Gaudio P Echeverria P. Placebo-controlled trial of co-trimoxazole for Cyclospora infections among travellers and foreign residents in Nepal.Lancet. 1995; 345: 691-693Abstract PubMed Scopus (0) Google Scholar AIDS patients should receive the same dose 4 times daily.50Pape JW Verdier RI Boncy M Boncy J Johnson Jr., WD Cyclospora infection in adults infected with HIV. 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In patients with immunosuppression, particularly AIDS, cryptosporidiosis may lead to severe diarrhea and wasting that requires specific treatment. An open, uncontrolled, prospective study indicated that oral paromomycin was partially effective in the treatment of Cryptosporidium in AIDS patients. Twenty-two of 24 treated patients showed clinical improvement with complete remission in 18 cases within 2–4 weeks, and significant improvement in 4 others.53Bissuel F Cotte L Rabodonirina M Rougier P Piens MA Trepo C. Paromomycin: an effective treatment for cryptosporidial diarrhea in patients with AIDS.Clin Infect Dis. 1994; 18: 447-449Crossref PubMed Google Scholar The recommended dose of paromomycin is 500 mg orally 4 times per day for 2 weeks. This nonabsorbable aminoglycoside unfortunately does not reach the biliary tree, which often serves as a reservoir of infection for recurrences of symptomatic bowel infection. Subcutaneous octreotide starting at a dose of 50–100 mg subcutaneously 3 times per day and titrated upward to 500 mg 3 times per day depending on the clinical response has been used with some success in AIDS patients with chronic cryptosporidial diarrhea.54Romeu J Miro JM Sirera G Mallolas J Arnal J Valls ME Tortosa F Clotet B Foz M. Efficacy of octreotide in the management of chronic diarrhoea in AIDS.AIDS. 1991; 5: 1495-1499Crossref PubMed Google Scholar, 55Liberti A Bisogno A Izzo E. Octreotide treatment in secretory and cyrptosporidial diarrhea in patients with acquired immunodeficiency syndrome (AIDS): clinical evaluation.J Chemother. 1992; 4: 303-305PubMed Google Scholar However, in a multicenter trial of octreotide in 129 AIDS-associated diarrhea patients, 38 of whom were infected with only Cryptosporidia, octreotide showed no beneficial effect.56Simon DM Cello JP Valenzuela J Levy R Dickerson G Goodgame R Brown M Lyche K Fessel WJ Grendell J et al.Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea.Gastroenterology. 1995; 108: 1753-1760Abstract Full Text PDF PubMed Scopus (54) Google Scholar Most patients in this study had CD4+ T-cell counts below 100/μL, a factor that may have limited effectiveness. This intracellular protozoa is an important pathogen in the HIV-infected population, in which it causes chronic diarrhea and sclerosing cholangitis. Most cases of diarrhea are caused by infection with Enterocytozoon bieneusi, with a minority caused by infection with E. intestinalis. Laboratory speciation of the infecting organism is required to guide therapy. A small, double-blind, placebo-controlled study in AIDS patients indicated that albendazole in a dose of 400 mg orally twice per day for 3 weeks is effective in clearing E. intestinalis infection.57Molina JM Chastang C Goguel J Michiels JF Sarfati C Desportes-Livage I Horton J Derouin F Modai J. Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial.J Infect Dis. 1998; 177: 1373-1377Crossref PubMed Google Scholar A larger retrospective study also confirmed that albendazole is effective in treating E. intestinalis, but not E. bieneusi, infections.58Leder K Ryan N Spelman D Crowe SM. Microsporidial disease in HIV-infected patients: a report of 42 patients and review of the literature.Scand J Infect Dis. 1998; 30: 331-338Crossref PubMed Scopus (20) Go
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