TRIPASS XR تري باس

 

Dorman SE et al. Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary

tuberculosis. Am J Respir Crit Care Med. 2009;180:273.

Bozeman L et al. Fluoroquinolone susceptibility among Mycobacterium tuberculosis isolates from the United

States and Canada. Clin Infect Dis. 2005;40:386.

Devasia RA et al. Fluoroquinolone resistance in Mycobacterium tuberculosis. The effect of duration and timing of

fluoroquinolone exposure. Am J Respir Crit Care Med. 2009;180:365.

Johnson R et al. Drug resistance in Mycobacterium tuberculosis. Curr Issues Mol Biol. 2006;8:97.

Williamson DA et al. Clinical failures associated with rpoB mutations in phenotypically occult multidrug-resistant

Mycobacterium tuberculosis. Int J Tuberc Lung Dis. 2012;16:216.

Morgan M et al. A commercial line probe assay for the rapid detection of rifampicin resistance in Mycobacterium

tuberculosis: a systematic review and meta-analysis. BMC Infect Dis. 2006;5:62.

Ling DI et al. GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis.

Eur Respir J. 2008;32:1165.

Lin S-YG et al. Rapid detection of isoniazid and rifampin resistance mutations in Mycobacterium tuberculosis

complex from cultures or smear-positive sputa by use of molecular beacons. J Clin Microbiol. 2004;42:4204.

Boehme CC et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med.

2010;363:1005.

Theron G et al. Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV

prevalence setting. Am J Respir Crit Care Med. 2011;184;132.

American Thoracic Society et al. Controlling tuberculosis in the United States. Am J Respir Crit Care Med.

2005;172:1169.

Cohn DL et al. A 62-dose, 6-month therapy for pulmonary and extrapulmonary tuberculosis: a twice-weekly,

directly observed, and cost-effective regimen. Ann Intern Med. 1990;112:407.

Tam CM et al. Rifapentine and isoniazid in the continuation phase of treating pulmonary tuberculosis. Initial

report. Am J Respir Crit Care Med. 1998;157(6, Pt 1):1726.

Benator D et al. Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for

treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: a randomised clinical trial.

100.

101.

102.

103.

104.

105.

106.

107.

108.

109.

110.

111.

112.

Lancet. 2002;360:528.

Bock NN et al. A prospective, randomized, double-blind study of the tolerability of rifapentine 600, 900, and 1,200

mg plus isoniazid in the continuation phase of tuberculosis treatment. Am J Respir Crit Care Med.

2002;165:1526.

Weiner M et al. Low isoniazid concentrations and outcome of tuberculosis treatment with once-weekly isoniazid

and rifapentine. Am J Respir Crit Care Med. 2003;167:1341.

Gillespie SH et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med.

2014;371:1577.

Merle CS et al. A four-month gatifloxacin-containing regimen for treating tuberculosis. N Engl J Med.

2014;371:1588.

Jindani A et al. High-dose rifapentine with moxifloxacin for pulmonary tuberculosis. N Engl J Med.

2014;371:1599.

Chaulk CP, Kazandjian VA. Directly observed therapy for treatment completion of pulmonary tuberculosis:

consensus statement of the Public Health Tuberculosis Guidelines Panel [published correction appears in

JAMA. 1998;280:134]. JAMA. 1998;279:943.

Jasmer RM et al. Tuberculosis treatment outcomes: directly observed therapy compared with self-administered

therapy. Am J Respir Crit Care Med. 2004;170:561.

Burman WJ et al. A cost-effectiveness analysis of directly observed therapy vs. self-administered therapy for

treatment of tuberculosis. Chest. 1997;112:63.

Mahmoudi A, Iseman MD. Pitfalls in the care of patients with tuberculosis. Common errors and their association

with the acquisition of drug resistance. JAMA. 1993;270:65.

Iseman MD et al. Directly observed treatment of tuberculosis: we can’t afford not to try it. N Engl J Med.

1993;328:576.

Jindani A et al. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir

Dis. 1980;121:939.

Chan SL et al. The early bactericidal activity of rifabutin measured by sputum viable counts in Hong Kong

patients with pulmonary tuberculosis. Tuber Lung Dis. 1992;73:33.

Sirgel FA et al. The early bactericidal activity of rifabutin in patients with pulmonary tuberculosis measured by

sputum viable counts: a new method of drug assessment. J Antimicrob Chemother. 1993;32:867.

Botha FJH et al. The early bactericidal activity of ethambutol, pyrazinamide, and the fixed combination of

isoniazid, rifampicin, and pyrazinamide (Rifater) in patients with pulmonary tuberculosis. S Afr Med J.

1996;86:155.

Dickinson JM, Mitchison DA. Experimental models to explain the high sterilizing activity of rifampin in the

chemotherapy of tuberculosis. Am Rev Respir Dis. 1981; 123(4, Pt 1):367.

Peloquin CA, Berning SE. Comment: intravenous streptomycin [letter]. Ann Pharmacother. 1993;27:1546.

Combs DL et al. USPHS Tuberculosis Short-Course Chemotherapy Trial 21: effectiveness, toxicity, and

acceptability: the report of final results. Ann Intern Med. 1990;112:397.

Khan A et al. Lack of weight gain and relapse risk in a large tuberculosis treatment trial. Am J Respir Crit Care

Med. 2006;174:344.

Arend SM et al. Comparison of two interferon-gamma assays and tuberculin skin test for tracing tuberculosis

contacts. Am J Respir Crit Care Med. 2007;175:618.

Diel R et al. Comparative performance of tuberculin skin test, QuantiFERON- TB-Gold In Tube Assay, and TSpot. TB test in contact investigations for tuberculosis. Chest. 2009;135:1010.

Schluger NW, BurzynskiJ. Recent advances in testing for latent TB. Chest. 2010;138:1456.

Horsburgh CR, Rubin EJ. Latent tuberculosis infection in the United States. N EnglJ Med. 2011;364:1441.

LoBue PA, Moser KS. Use of isoniazid for latent tuberculosis infection in a public health clinic. Am J Respir

Crit Care Med. 2003;168:443.

Horsburgh CR Jr et al. Latent TB infection treatment acceptance and completion in the United States and

Canada. Chest. 2010;137:401.

Menzies D et al. Treatment completion and costs of a randomized trial of rifampin for 4 months versus isoniazid

for 9 months. Am J Respir Crit Care Med. 2004;170:445.

Menzies D et al. Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent

tuberculosis infection: a randomized trial. Ann Intern Med. 2008;149:689.

Reichman LB et al. Considering the role of four months of rifampin in the treatment of latent tuberculosis

infection. Am J Respir Crit Care Med. 2004;170:832.

113.

114.

115.

116.

117.

118.

119.

120.

121.

122.

123.

124.

125.

126.

127.

128.

129.

130.

131.

132.

133.

134.

135.

136.

137.

138.

139.

140.

141.

142.

143.

144.

145.

Fountain FF et al. Rifampin hepatotoxicity associated with treatment of latent tuberculosis infection. Am J Med

Sci. 2009;337:317.

Holland DP et al. Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection. Am J

Respir Crit Care Med. 2009;179:1055.

Sterling TR et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med.

2011;365:2155.

Centers for Disease Control and Prevention. Recommendations for use of an isoniazid-rifapentine regimen with

direct observation to treat latent Mycobacterium tuberculosis infection. Morb Mortal Wkly Rep. 2011;60:1650.

Saukkonen JJ et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care

Med. 2006;174:935.

Moulding T. Isoniazid-associated hepatitis deaths: a review of available information [letter]. Am Rev Respir Dis.

1992;146:1643.

Ellard GA. Variations between individuals and populations in the acetylation of isoniazid and its significance for

the treatment of pulmonary tuberculosis. Clin Pharmacol Ther. 1976;19(5, Pt 2):610.

Ellard GA et al. The hepatic toxicity of isoniazid among rapid and slow acetylators of the drug. Am Rev Respir

Dis. 1978;118:628.

Kopanoff DE et al. Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study. Am

Rev Respir Dis. 1978;117:991.

Girling DJ. Adverse effects of antituberculosis drugs. Drugs. 1982;23:56.

Steele MA et al. Toxic hepatitis with isoniazid and rifampin: a meta-analysis. Chest. 1991;99:465.

Nolan CM et al. Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public

health tuberculosis clinic. JAMA. 1999;281:1014.

Centers for Disease Control and Prevention. Severe isoniazid-associated liver injuries among persons being

treated for latent tuberculosis infection—United States, 2004–2008. Morb Mortal Wkly Rep. 2010;59:224.

Wright JM et al. Isoniazid-induced carbamazepine toxicity and vice versa: a double drug interaction. N Engl J

Med. 1982;307:1325.

Baciewicz AM et al. Update on rifampin and rifabutin drug interactions. Am J Med Sci. 2008;335:126.

Sanders WE Jr. Rifampin. Ann Intern Med. 1976;85:82.

Zierski M, Bek E. Side-effects of drug regimens used in short-course chemotherapy for pulmonary tuberculosis:

a controlled clinicalstudy. Tubercle. 1980;61:41.

Girling DJ. Adverse reactions to rifampicin in antituberculosis regimens. J Antimicrob Chemother. 1977;3:115.

Lee CH, Lee CJ. Thrombocytopenia—a rare but potentially serious side effect of initial daily and interrupted use

of rifampicin. Chest. 1989;96:202.

Berning SE, Iseman MD. Rifamycin-induced lupus syndrome. Lancet. 1997;349:1521.

Bennett WM et al. Drug therapy in renal failure: dosing guidelines for adults. Part I: antimicrobial agents,

analgesics. Ann Intern Med. 1980;93:62.

Andrew OT et al. Tuberculosis in patients with end-stage renal disease. Am J Med. 1980;68:59.

Semvua HH et al. Pharmacological interactions between rifampicin and antiretroviral drugs: challenges and

research priorities for resource-limited settings. Ther Drug Monit. 2015;37:22.

Niemi M et al. Pharmacokinetic interactions with rifampicin: clinical relevance. Clin Pharmacokinet.

2003;42:819.

Citron KM, Thomas GO. Ocular toxicity from ethambutol. Thorax. 1986;41:737.

Schild HS, Fox BC. Rapid-onset reversible ocular toxicity from ethambutol therapy. Am J Med. 1991;90:404.

Alvarez KL, Krop LC. Ethambutol-induced ocular toxicity revisited [letter]. Ann Pharmacother. 1993;27:102.

Van den Brande P. Revised guidelines for the diagnosis and control of tuberculosis: impact on management in

the elderly. Drugs Aging. 2005;22:663.

Rajagopalan S, Yoshikawa TT. Tuberculosis in long-term-care facilities. Infect Control Hosp Epidemiol.

2000;21:611.

Stead WW et al. Tuberculosis as an endemic and nosocomial infection among elderly in nursing homes. N EnglJ

Med. 1985;312:1483.

Chan CH et al. The effect of age on the presentation of patients with tuberculosis. Tuber Lung Dis.

1995;76:290.

Rajagopalan S. Tuberculosis and aging: a global health problem. Clin Infect Dis. 2001;33:1034.

van den Brande P et al. Aging and hepatotoxicity of isoniazid and rifampin in pulmonary tuberculosis. Am J

Respir Crit Care Med. 1995;152(5, Pt 1):1705.

146.

147.

148.

149.

150.

151.

152.

153.

154.

155.

156.

157.

158.

159.

160.

161.

162.

163.

164.

165.

166.

167.

168.

169.

170.

171.

Goble M et al. Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin. N Engl

J Med. 1993;328:527.

Berning SE et al. Malabsorption of antituberculosis medications by a patient with AIDS. N Engl J Med.

1992;327:1817.

Driver CR et al. Factors associated with tuberculosis treatment interruption in New York City. J Public Health

Manag Pract. 2005;11:361.

Di Perri G, Bonora S. Which agents should we use for the treatment of multidrug-resistant Mycobacterium

tuberculosis? J Antimicrob Chemother. 2004;54:593.

Burgos M et al. Treatment of multidrug-resistant tuberculosis in San Francisco: an outpatient-based approach.

Clin Infect Dis. 2005;40:968.

Holtz TH et al. Time to sputum culture conversion in multidrug-resistant tuberculosis: predictors and relationship

to treatment outcome. Ann Intern Med. 2006;144:650.

Winston CA et al. Treatment duration for patients with drug-resistant tuberculosis, United States. Emerg Infect

Dis. 2012;18:1201.

Van Deun A et al. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant

tuberculosis. Am J Respir Crit Care Med. 2010;182:684.

Berning SE et al. Long-term safety of ofloxacin and ciprofloxacin in the treatment of mycobacterial infections.

Am J Respir Crit Care Med. 1995;151:2006.

Peloquin CA et al. Levofloxacin for drug-resistant Mycobacterium tuberculosis. Ann Pharmacother.

1998;32:268.

Codecasa LR et al. Long-term moxifloxacin in complicated tuberculosis patients with adverse reactions or

resistance to first line drugs. Respir Med. 2006;100:1566.

Worley MV, Estrada SJ. Bedaquiline: a novel antitubercular agent for the treatment of multidrug-resistant

tuberculosis. Pharmacotherapy. 2014;34:1187.

Diacon AH et al. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med.

2009;360:2397.

Diacon AH et al. Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrugresistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance. Antimicrob

Agents Chemother. 2012;56:3271.

Diacon AH et al. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med.

2014;371:723.

Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and

treatment of opportunistic infections in HIV-infected adults and adolescents.

https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed October 10, 2015.

Luetkemeyer AF et al. Comparison of an interferon-gamma release assay with tuberculin skin testing in HIVinfected individuals. Am J Respir Crit Care Med. 2007;175:737.

Dewan PK et al. Low sensitivity of a whole-blood interferon-γ release assay for detection of active tuberculosis.

Clin Infect Dis. 2007;44:69.

Menzies D et al. New tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and

recommendations for research [published correction appears in Ann Intern Med. 2007;146:688]. Ann Intern

Med. 2007;146:340.

Monkongdee P et al. Yield of acid-fast smear and mycobacterial culture for tuberculosis diagnosis in people with

human immunodeficiency virus. Am J Respir Crit Care Med. 2009;180:903.

Rich ML et al. Representative drug susceptibility patterns for guiding design of retreatment regimens for MDRTB. Int J Tuberc Lung Dis. 2006;10:290.

Burman WJ, Jones BE. Treatment of HIV-related tuberculosis in the era of effective antiretroviral therapy. Am

J Respir Crit Care Med. 2001;164:7.

Centers for Disease Control and Prevention. Acquired rifamycin resistance in persons with advanced HIV

disease being treated for active tuberculosis with intermittent rifamycin-based regimens. Morb Mortal Wkly

Rep. 2002;51:214.

Swaminathan S et al. Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected

patients with tuberculosis: a randomized clinical trial. Am J Respir Crit Care Med. 2010;181:743.

Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs. 2002;62:2169.

Blanc FX et al. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N

EnglJ Med. 2011;365:1471.

172.

173.

174.

175.

176.

177.

178.

179.

180.

181.

182.

183.

184.

185.

186.

187.

188.

189.

190.

191.

192.

193.

194.

195.

196.

197.

198.

Havlir DV et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med.

2011;365:1482.

Abdool Karim SS et al. Integration of antiretroviral therapy with tuberculosis treatment. N Engl J Med.

2011;365:1492.

Hammer SM et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society

—USA panel. JAMA. 2006;296:827.

Lopez-Cortes LF et al. Pharmacokinetic interactions between efavirenz and rifampicin in HIV-infected patients

with tuberculosis. Clin Pharmacokinet. 2002;41:681.

Cohen K et al. Effect of rifampicin-based antitubercular therapy and the cytochrome P450 2B6 516G>T

polymorphism on efavirenz concentrations in adults in South Africa. Antivir Ther. 2009;14:687.

Ramachandran G et al. CYP2B6 G516T polymorphism but not rifampin coadministration influences steady-state

pharmacokinetics of efavirenz in human immunodeficiency virus-infected patients in South Africa. Antimicrob

Agents Chemother. 2009;53:863.

Pape JW et al. Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV

infection. Lancet. 1993;342:268.

Mnyani CN, McIntyre JA. Tuberculosis in pregnancy. Br J Obstet Gynecol. 2011;118:226.

Brost BC, Newman RB. The maternal and fetal effects of tuberculosis therapy. Obstet Gynecol Clin North Am.

1997;24:659.

Frieden TR et al. Tuberculosis. Lancet. 2003;362:887.

Vallejo JG, Starke JR. Tuberculosis and pregnancy. Clin Chest Med. 1992;13:693.

Bergeron KG et al. Tuberculosis in pregnancy: current recommendations for screening and treatment in the

USA. Expert Rev Anti Infect Ther. 2004;2:589.

Shin S et al. Treatment of multidrug-resistant tuberculosis during pregnancy: a report of 7 cases. Clin Infect Dis.

2003;36:996.

Drobac PC et al. Treatment of multidrug-resistant tuberculosis during pregnancy: long-term follow-up of 6

children with intrauterine exposure to second-line agents. Clin Infect Dis. 2005;40:1689.

Powell DA, Hunt WG. Tuberculosis in children: an update. Adv Pediatr. 2006;53:279.

Starke JR Correa AG. Management of mycobacterial infection and disease in children. Pediatr Infect Dis J.

1995;14:455.

Pediatric Tuberculosis Collaborative Group. Targeted tuberculin skin testing and treatment of latent tuberculosis

infection in children and adolescents. Pediatrics. 2004;114(Suppl 4):1175.

Golden MP, Vikram HR. Extrapulmonary tuberculosis: an overview. Am Fam Physician. 2005;72:1761.

Garg RK. Tuberculosis of the central nervous system. Postgrad Med J. 1999;75:133.

Holdiness MR. Cerebrospinal fluid pharmacokinetics of the antituberculosis drugs. Clin Pharmacokinet.

1985;10:532.

Dooley DP et al. Adjunctive corticosteroid therapy for tuberculosis: a critical reappraisal of the literature. Clin

Infect Dis. 1997;25:872.

Heysell HK et al. Therapeutic drug monitoring for slow response to tuberculosis treatment in a state control

program, Virginia, USA. Emerg Inf Dis. 2010;16:1546.

Magis-Escurra C et al. Therapeutic drug monitoring in the treatment of tuberculosis patients. Pulm Pharmacol

Ther. 2012;25:83.

Babalik A et al. Therapeutic drug monitoring in the treatment of active tuberculosis. Can Respir J. 2011;18:225.

Prahl JB et al. Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs: a

prospective observationalstudy. J Antimicrob Chemother. 2014;69:2841.

Pasipanodya JG et al. Serum drug concentrations predictive of pulmonary tuberculosis outcomes. J Infect Dis.

2013;208:1464.

Alsultan A, Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis: an update. Drugs.

2014;74:839.

p. 1445

The most common complication of any diarrheal illness is loss of fluids

and electrolytes, which in extreme cases can lead to hypovolemia,

shock, and death. Depending on the degree of dehydration, fluid and

electrolyte losses are replaced intravenously or orally.

Case 69-1 (Questions 1, 2)

Classification of infectious diarrheas as either an inflammatory or

noninflammatory diarrheal illness provides a basis for preparing a

focused list of suspected pathogens, thus guiding the overall diagnostic

and therapeutic plan.

Case 69-1 (Questions 3–4)

Vibrio cholerae 01 and 0139 are toxigenic strains of Vibrio species,

which cause epidemic cholera; severe dehydration requiring vigorous

fluid replacement may be necessary. Non-cholera Vibrio species do not

possess the virulence factors required to cause epidemic cholera.

Antimicrobial treatment differs between toxigenic and non-toxigenic

Vibrio species.

Case 69-2 (Questions 1–3),

Case 69-3 (Questions 1, 2)

Salmonella species are classified as non-typhoidal and typhoidal

salmonellae. Non-typhoidalsalmonellae may cause the clinical

syndromes of gastroenteritis, bacteremia, and localized infection,

whereas typhoidalsalmonellae may cause typhoid fever and chronic

carriage. The role of antimicrobials in the management of salmonellosis

is based on the clinicalsyndrome, its severity, and underlying health

problems of infected persons.

Case 69-7 (Question 1),

Case 69-8 (Questions 1, 2),

Case 69-9 (Question 1),

Case 69-10 (Question 1),

Case 69-11 (Questions 1–7)

Severe dysentery caused by Shigella species is most commonly caused

by Shigella dysenteriae, whereas a milder illness is typically caused by

Shigella sonnei. Antimicrobials alleviate the symptoms of shigellosis, and

decrease the period of time that shigellae can be spread by person-toperson contact.

Case 69-12 (Questions 1–5),

Case 69-13 (Question 1)

Fluoroquinolone-resistance in Campylobacter species is a common

finding in both developed and underdeveloped areas of the world; when

indicated, macrolide antimicrobials are recommended.

Case 69-14 (Questions 1–3)

Travelers to destinations where acquisition of Travelers’ diarrhea (TD)

is a concern should bring a travel kit including medications (e.g.,

loperamide and antimicrobials) and instructions for self-treatment at the

onset of illness. The selected antimicrobial depends on the area of

Case 69-15 (Questions 1–6)

travel. Long-term postinfectious complications of TD may occur in

some returning travelers.

Escherichia coli O157:H7 is a specific toxin-producing strain of E. coli

bacteria that can lead to the severe sequelae of hemolytic uremic

syndrome.

Case 69-16 (Questions 3, 4)

Clostridium difficile infection causes a wide range of severity of illness.

Mild-to-moderate disease is typically treated with metronidazole as firstline therapy, and oral vancomycin is preferred for severe disease.

Case 69-17 (Question 6)

Severe C. difficile infection can be life-threatening and often

necessitates multiple therapeutic interventions.

Case 69-18 (Questions 4, 5)

p. 1446

p. 1447

PREVALENCE AND ETIOLOGY

Worldwide, diarrhea accounts for more than 2.5 million deaths annually,

1 mainly

affecting infants and children living in poverty.

2 Prolonged episodes of diarrhea lead

to malnutrition and in children contribute to impaired growth and developmental

delay.

2

In the United States, about 48 million foodborne diarrheal illnesses occur

each year, resulting in 128,000 hospitalizations and 3,000 deaths.

3

Infectious diarrhea is caused by the ingestion of food or water contaminated with

pathogenic microorganisms (e.g., bacteria, viruses, protozoa, or fungi) or their toxins

(Table 69-1).

2

In the United States, noroviruses account for about 50% of diarrheal

outbreaks, while common bacterial pathogens include Campylobacter, non-typhoidal

Salmonella, Shigella, and Shiga toxin–producing Escherichia coli.

3

Table 69-1

Predisposing Factors, Symptoms, and Therapy of Gastrointestinal Infections

Pathogen

Predisposing

Factors Symptoms

Diagnostic

Evaluations

Drug of

Choice

a

,

c Alternatives

a

,

Salmonella (nontyphoidal)

b

Ingestion of

contaminated

poultry, raw milk,

custards, and cream

fillings; foreign

travel

Nausea, vomiting,

diarrhea, cramps,

fever,

tenesmus.Incubation:

6–72 hours

Fecal

leukocytes,

stool culture

Fluoroquinolone,

azithromycin,

third-generation

cephalosporins

Amoxicillin,

TMP–SMX

Salmonella

(typhoidal)

Ingestion of

contaminated food;

foreign travel

High fever,

abdominal pain,

headache, dry cough

Fecal

leukocytes,

stool culture,

Fluoroquinolone,

azithromycin,

third-generation

TMP–SMX,

amoxicillin

blood culture cephalosporins

Shigella Ingestion of

contaminated salad,

raw vegetables,

swimming in water

contaminated with

sewage; foreign

travel

Fever, dysentery,

cramps,

tenesmus.Incubation:

24–48 hours

Fecal

leukocytes,

stool culture

Fluoroquinolone,

azithromycin,

ceftriaxone

TMP–SMX,

ampicillin

Campylobacter Contaminated eggs,

raw milk, or poultry;

foreign travel

Mild-to-severe

diarrhea; fever,

systemic malaise.

Incubation: 24–72

hours

Fecal

leukocytes,

stool culture

Erythromycin,

azithromycin

–

Clostridium

difficile

Antibiotics,

antineoplastics

Mild-to-severe

diarrhea, cramps

C. difficile

toxin, C.

difficile

culture,

colonoscopy

Metronidazole Vancomycin

Staphylococcal

food poisoning

Custard-filled

bakery products,

canned food,

processed meat, ice

cream

Nausea, vomiting,

salivation, cramps,

diarrhea; usually

resolves in 8

hours.Incubation: 2–

6 hours

– Supportive

therapy only

–

Travelers’

diarrhea

(Enterotoxigenic

Escherichia coli,

Campylobacter)

Contaminated food

(vegetables and

cheese), water;

foreign travel

Nausea, vomiting,

mild-to-severe

diarrhea, cramps

Stool culture See Table 69-3 –

Shiga

toxin–producing

Escherichia coli

(E. coli

O157:H7)

Beef, raw milk,

water

Diarrhea, headache,

bloody

stoolsIncubation: 48–

96 hours

Stool cultures

on

MacConkey’s

sorbitol

Supportive

therapy only

–

Cryptosporidiosis Immunosuppression,

day-care centers,

contaminated water,

animal handlers

Mild-to-severe

diarrhea (chronic or

self-limited); large

fluid volume

Stool

screening for

oocytes,

PCR, ELISA

See Chapter 77,

Opportunistic

Infections in

HIV-Infected

Patients

–

Viral

gastroenteritis

Community-wide

outbreaks,

contaminated food

Nausea, diarrhea

(self-limited),

cramps. Incubation:

16–48 hours

Special viral

studies

Supportive

therapy only

–

aSources: Navaneethan U, Giannella RA. Mechanisms of infectious diarrhea. Nat Clin Pract Gastroenterol Hepatol

2008;5:637; DuPont HL. Acute infectious diarrhea in immunocompetent adults. N Engl J Med. 2014;370:1532. See

text for doses and duration of therapy.

bNot all cases require antibiotic therapy. See text for details.

c

If susceptible. See text for details.

ELISA, enzyme-linked immunosorbent assay; PCR, polymerase chain reaction; TMP–SMX, trimethoprim–

sulfamethoxazole.

p. 1447

p. 1448

This chapter focuses on the diagnosis and management of the common microbial

causes of acute infectious diarrhea.

DEFINITIONS

Diarrhea is often defined as three or more episodes of loose stools or any loose stool

with blood during a 24-hour period, which may be accompanied by nausea, vomiting,

or abdominal cramping.

3 The duration of illness is considered acute if symptoms are

present for less than 2 weeks duration, persistent if symptoms last for 14 to 29 days,

and chronic if symptoms last ≥30 days.

3 Classifying diarrheal syndromes as either a

noninflammatory (watery diarrhea) or an inflammatory (bloody diarrhea) illness

provides a basis for predicting the most likely microbial cause for the intestinal

illness.

1

PATHOGENESIS

The pathogenesis of infectious diarrhea involves an interplay among bacterial

virulence factors, host factors, and predisposing factors to infection. Diarrhea is

more likely to occur in the setting in which an imbalance among these factors favors

the enteropathogen.

Bacterial Virulence Factors

Enteropathogens possess virulence factors that contribute to the organism’s

pathogenicity.

2 Enterotoxins targeting the small bowel cause net movement of fluid

into the gut lumen, leading to voluminous watery stools and potentially lifethreatening dehydration. Cytotoxins targeting the colon cause direct mucosal damage,

leading to fever and bloody diarrhea. Invasive properties of Shigella species and

invasive strains of E. coli allow these bacteria to invade and destroy epithelial cells,

causing bloody or mucoid stools. Some enteropathogens induce a vigorous host

response through the release of proinflammatory cytokines from intestinal epithelial

cells, leading to diarrhea. Finally, adhesions allow enteropathogens to attach to and

colonize the gastrointestinal (GI) mucosa, facilitating toxin delivery, invasion,

dissemination, or host cell lysis.

2

Host Defenses

The human GI tract possesses numerous defense mechanisms to protect against

enteric infection. Normal bacterial flora compete for space and nutrients with

potentially pathogenic organisms, or produce substances, e.g., short-chain fatty acids,

that are inhibitory to enteropathogens.

2 Gastric acidity of the stomach prevents acidsusceptible pathogens from passing from the stomach into the intestinal tract, whereas

gastrointestinal mucus and mucosal tissue integrity provide physical barriers against

infection. Intestinal immunity includes defensins that are bactericidal to some

enteropathogens, local production of antibodies, and toll-like receptors that

recognize enteropathogens and activate the immune response.

2

Intestinal peristalsis

moves bacteria and their toxins along and out of the GI tract. Finally, specific host

genetic factors are protective against enteric infection.

3

Predisposing Factors

Inadequate sanitation facilities increase the risk that local inhabitants and travelers

will be exposed to contaminated food and water. Outbreaks of foodborne or

waterborne illnesses in both industrialized and developing countries facilitate the

spread of infectious organisms. Industrialized countries that rely on imported food

items risk the possibility of importation of contaminated food products.

4

Immunocompromised hosts, such as organ transplant recipients and patients receiving

immunosuppressive therapies, are more susceptible to intestinal infection.

Institutional settings such as day-care centers, hospitals, and extended-care facilities

are high-risk settings for dissemination of disease. Finally, poor personal hygiene is

a risk for infectious diarrhea.

Table 69-2

Pharmacologic Agents that May Promote Gastrointestinal Infection

Drug Mechanism

Antacids, H2

-receptor antagonists, proton-pump

inhibitors

Increase of gastric pH; passage of viable pathogens to

lower gut

Antibiotics Alteration of intestinal flora

Cancer chemotherapy Unclear but may include the antimicrobial activity of

chemotherapeutic agents, or chemotherapy-induced

intestinal damage and necrosis favoring an anaerobic

environment for the growth of C. difficile.

Source: DuPont HL. Acute infectious diarrhea in immunocompetent adults. N Engl J Med. 2014;370:1532; Cohen

SH et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society of

Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect

Control Hosp Epidemiol. 2010;31:431; Anand A, Glatt AE. Clostridium difficile infection associated with

antineoplastic chemotherapy: a review. Clin Infect Dis. 1993;17:109.

The use of pharmacologic agents, e.g., drugs that increase gastric pH (Table 69-2),

increases the risk for infection with acid-susceptible pathogens such as Salmonella

species and Vibrio cholerae.

5 The use of proton-pump inhibitors predisposes patients

to Clostridium difficile diarrhea.

MANAGEMENT OVERVIEW

Rehydration Therapy

The most common complication of any diarrheal illness is loss of fluids and

electrolytes, which in extreme cases can lead to hypovolemia, shock, and death.

1

Depending on the degree of dehydration, fluid and electrolyte losses are replaced

intravenously (IV) or orally. Once replacement of fluid and electrolyte losses is

completed, additional laboratory tests and drug therapies can be considered.

Laboratory Tests

Inflammatory diarrheal illnesses are characterized by the presence of bloody or

mucoid stools. Therefore, stool specimens with red blood cells (RBCs) or occult

blood, or those that contain large numbers of white blood cells, suggest infection

attributable to invasive pathogens.

6

Identification of bacterial toxins in stool specimens is a useful diagnostic tool. For

example, because only the toxigenic strains of C. difficile are pathogenic, the

presence or absence of bacterial toxins in stool specimens is more important than a

positive culture for the organism.

7

p. 1448

p. 1449