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7/18/2015 1 Antibiotic Therapy in Diarrhea M.Emadoleslami MD • Excessive loss of fluid and electrolyte in the stool • • Acute diarrhea is defined as sudden onset of excessively loose stools of >10 mLlkg/day in infants and >200 g/24 hr in older children, which lasts <14 days When the episode lasts>14 days, it is called chronic or persistent diarrhea 7/18/2015 3 • Normally, a young infant has 5 ml/kg/day of stool output • The greatest volume of intestinal water is absorbed in the small bowel; the colon concentrates intestinal contents against a high osmotic gradient • Disorders that interfere with absorption in the small bowel tend to produce voluminous diarrhea, whereas disorders compromising colonic absorption produce lower-volume diarrhea 7/18/2015 4 Shigella 7/18/2015 5 An acute invasive enteric infection clinically manifested by diarrhea that is often bloody The term dysentery, syndrome of bloody diarrhea with fever, abdominal cramps, rectal pain, and mucoid stools Bacillary dysentery is a term often used to distinguish dysentery caused by Shigella from amoebic dysentery caused by Entamoeba histolytica The pathologic changes of shigellosis take place primarily in the colon 7/18/2015 6 Diagnosis Presumptive diagnosis : fecal leukocytes (usually >50 or 100 PMNs per high power field, confirming the presence of colitis), fecal blood, and peripheral blood of leukocytosis, a dramatic left shift (often with more bands than segmented neutrophils) 5,000-15,000 cells', leukopenia, eukemoid reactions Transport media should be used if specimens cannot be cultured promptly Multiple fecal cultures improve the yield of Shigella In toxic children, blood cultures should be obtained, especially in very young or malnourished infants because of their increased risk of bacteremia 7/18/2015 7 Treatment The first concern in a child with suspected shigellosis should be for fluid and electrolyte correction and maintenance Drugs that retard intestinal motility should not be used because of the risk of prolonging the illness A high-protein diet during convalescence enhances growth in the following 6 mo 20 mg elemental zinc for 14 d, decrease the duration of diarrhea, improve weight gain during recovery and immune response to the Shigella, and decrease diarrheal disease in the subsequent 6 mo in malnourished children 7/18/2015 8 The Use of Antibiotics * • Some authorities recommend withholding antibacterial therapy because of the self-limited nature of the infection, the cost of drugs, and the risk of emergence of resistant organisms • Empirical treatment of all children in whom shigellosis is strongly suspected • Even if not fatal, the untreated illness can cause a child to be quite ill for weeks; chronic or recurrent diarrhea can ensue • Malnutrition can develop or worsen during prolonged illness, particularly in children in developing countries 7/18/2015 9 ** Shigella strains are often resistant to ampicillin and TMP-SMX Ceftriaxone 50 mg/kg/24 hr as a single daily dose IV Cefixime Nalidixic acid(55 mg/kg/24 hr orally divided 4 times/day) is also an acceptable alternative drug Azithromycin (12 mg/kg/24 hr orally for the first day, followed by 6 mg/kg/24 hr for the next 4days) Ciprofloxacin (30 mg/kg/24 hr divided into 2 doses) Oral 1st and 2nd-generation cephalosporins are inadequate 7/18/2015 10 *** Ciprofloxacin now the drug of choice recommended by WHO for all patients with bloody diarrhea,irrespective of their ages Although quinolones have been reported to cause arthropathy in immature animals, the risk of joint damage in children, minimal Some experts recommend that these agents be reserved for seriously ill children with bacillary dysentery due to an organism that is suspected or known to be resistant to other agents, because overuse of quinolones promotes development of resistance to these drugs Treatment in general is for a 5-day course 7/18/2015 11 **** • Treatment of patients in whom Shigella infection is suspected on clinical grounds of should be initiated when they are first evaluated • Stool culture is obtained to exclude other pathogens and to assist in antibiotic changes should a child fail to respond to empirical therapy • A child who has typical dysentery and who responds to initial empirical antibiotic treatment should be continued on that drug for a full 5-day course even if the stool culture is negative 7/18/2015 12 Salmonella 7/18/2015 13 • Salmonellosis is a common and widely distributed food-borne disease • A gastroenteritis of rapid onset and brief duration, in contrast to typhoid, which has a considerably longer incubation period and duration of illness and in which systemic illness predominates and only a small proportion of children get diarrhea 7/18/2015 14 Diagnosis On clinical correlation of the presentation and culture of and subsequent identification of Salmonella organisms from feces or other body fluid Cultures of stools have higher yields than rectal swabs In children with nontyphoidal Salmonella gastroenteritis, prolonged fever lasting >5 days and young age should be recognized as risk factors closely associated with development of bacteremia 7/18/2015 15 Treatment Infants (<3 mo of age) and that of disseminated infection in HIV, malignancies, immunosuppressive therapy, sickle cell anemia, ), these children must receive an appropriate empirically chosen antibiotic until culture results are available In children with gastroenteritis, rapid clinical assessment, correction of dehydration and electrolyte disturbances, and supportive care, are key Antibiotics are not generally recommended for the treatment of isolated uncomplicated Salmonella gastroenteritis because they may suppress normal intestinal flora and prolong both the excretion of Salmonella Infections with suspected drug-resistant Salmonella should be closely monitored and treated with appropriate antimicrobial therapy 7/18/2015 16 Typhoid Fever 7/18/2015 17 Diagnosis Blood culture in the course of the disease, and stool and urine culture results become positive after the 1st wk The stool culture result is also occasionally positive during the incubation period Although bone marrow cultures may increase the likelihood of bacteriologic confirmation of typhoid, collection of the specimens is difficult and relatively invasive The classic Widal test measures antibodies against 0 and H antigens of S. Typhi but lacks sensitivity and specificity in endemic areas. Because many false-positive and false-negative results occur, diagnosis of typhoid fever by Widal test alone is prone to error Despite these innovations, the mainstay of diagnosis of typhoid remains clinical in much of the developing world, and several diagnostic algorithms have been evaluated in endemic areas 7/18/2015 18 Treatment • The vast majority of children with typhoid can be managed at home with oral antibiotics and close medical follow-up for complications or failure of response to therapy • Patients with persistent vomiting, severe diarrhea, and abdominal distention may require hospitalization and parenteral antibiotic therapy • Adequate rest, hydration, and attention are important to correct fluid and electrolyte imbalance • Acetaminophen 10-15 mg/kg every 4-6 hr PO • A soft, easily digestible diet should be continued unless the patient has abdominal distention or ileus 7/18/2015 19 Antibiotic therapy, critical to minimize complications Traditional therapy with either chloramphenicol or amoxicillin is associated with relapse rates of 5-15% and 4-8% Use of the quinolones and third-generation cephalosporins is associated with higher cure rates The antibiotic treatment of typhoid fever in children is also influenced by the prevalence of antimicrobial resistance Over the past 2 decades, emergence of multidrug-resistant strains of S. Typhi has necessitated treatment with fluoroquinolones 7/18/2015 20 • Some investigators have suggested that children with typhoid should be treated with fluoroquinolones like adults • Others have questioned this approach on the basis of the potential development of further resistance to fluoroquinolones and the fact that quinolones are still not approved for widespread use in typhoid fever • Supportive treatment and maintenance of appropriate fluid and electrolyte balance 7/18/2015 21 Cholera 7/18/2015 22 Cholera is a rapidly dehydrating diarrheal disease that can lead to death, if appropriate treatment is not provided immediately Although rare in industrialized countries, cholera has a propensity to cause outbreaks in areas with poor hygiene and inadequate sanitation and water facilities These outbreaks may be explosive, especially when they occur in populations residing in crowded conditions, such as refugee camps 7/18/2015 23 Clinical Manifestations Most cases of cholera are mild Among symptomatic cases, 20% develop severe dehydration,rapidly lead to death Incubation period 1-3 days (several hours to 5 d), acute watery diarrhea and vomiting ensues The onset may be sudden, profuse watery diarrhea, but some, anorexia and abdominal discomfort and the stool may initially be brown Diarrhea can progress to painless purging of profuse rice-water stools with a fishy smell, which is the hallmark of the disease 7/18/2015 24 Vomiting with clear watery fluid is usually present at the onset of the disease This purging leads to dehydration manifested by decreased urine output, sunken fontanels , sunken eyes, absence of tears, dry oral mucosa, shriveled hands and feet (washerwoman's hands), poor skin turgor, thready pulse, tachycardia, hypotension, and vascular collapse Patients with metabolic acidosis can present with typical Kussmaul breathing Although patients may be initially thirsty and awake, they rapidly progress to obtundation and coma. If fluid losses are not rapidly corrected, death can occur within hours 7/18/2015 25 Laboratory Findings Findings associated with dehydration such as elevated urine specific gravity and hemoconcentration are evident Hypoglycemia is a common finding due to decreased food intake during the acute illness Serum potassium may be initially normal or even high in the presence of metabolic acidosis; however, as the acidosis is corrected, hypokalemia can become evident Metabolic acidosis due to bicarbonate loss is a prominent finding in severe cholera 7/18/2015 26 Diagnosis Laboratory confirmation is necessary for epidemiologic surveillance V. cholerae may be isolated from stools, vomitus, or rectal swabs Specimens may be transported on Cary-Blair media, if they cannot be processed immediately Stool examination reveals few fecal leukocytes and erythrocytes because cholera does not cause inflammation 7/18/2015 27 DX & D.DX In children who have acute watery diarrhea with severe dehydration and have recently traveled to an area known to have cholera, the disease may be suspected pending laboratory confirmation Cholera differs from other diarrheal disease in that it often occurs in large outbreaks affecting both adults and children Diarrhea due to other etiologic causes (e.g., enterotoxigenic Escherichia coli or rotavirus) may be difficult to distinguish from cholera clinically Microbiologic isolation of V. cholerae remains the gold standard for diagnosis 7/18/2015 28 Treatment Rehydration, Effective and timely case management considerably decreases mortality Children with mild or moderate dehydration may be treated with ORS unless the patient is in shock, is obtunded, or has intestinal ileus Vomiting is not a contraindication to ORS Severely dehydrated patients require intravenous fluid, ideally with lactated Ringer solution Feeding should not be withheld during diarrhea Frequent, small feedings are better tolerated than less frequent, large feedings 7/18/2015 29 Close monitoring during the first 24 hr of illness After rehydration, patients have to be reassessed every 1-2 hr, or more frequently if profuse diarrhea is ongoing As soon as vomiting stops (4-6 hr after initiation of rehydration therapy), an antibiotic must be administrated Zinc , as soon as vomiting stops Zinc supplementation among children <5 y, shorten the duration of diarrhea and reduce subsequent diarrhea episodes when given daily for 14 d at the time of the illness For children <6 mo of age, 10 mg of oral zinc daily, 2 wk Children aged 6 mo to 12 yr, 20 mg of oral zinc may be given daily, 2 wk 7/18/2015 30 Antimicrobials For Suspected Cholera Cases With Severe Dehydration Doxycycline (adults and older children) 300 mg given as a single dose Or Tetracycline 12.5 mg/kg/dose 4 times/day 3 days (up to 500 mg per dose, 3 days) Erythromycin 12.5 mg/kg/dose 4 times a day, 3 days (up to 250 mg 4 times a day x 3 days) 7/18/2015 31 o Antibiotics shorten the duration of illness, decrease fecal excretion of vibrios, decrease the volume of diarrhea, and reduce the fluid requirement during rehydration o Single-dose doxycycline increases compliance; there have been increasing reports of resistance to tetracyclines. Ciprofloxacin, azithromycin, and TMP/SMX are also effective against cholera o Cephalosporins and aminoglycosides are not clinically effective 7/18/2015 32 E.Coli 7/18/2015 33 Treatment Appropriate fluid and electrolyte therapy Oral replacement and maintenance with rehydration solution Prolonged Withholding of feeding can lead to chronic diarrhea and malnutrition After refeeding, continued supplementation with oral rehydration fluids is appropriate to prevent recurrence of dehydration Early refeeding (within 6-8 hr of initiating rehydration) with breast milk or infant formula or solid foods should be encouraged In malnourished child, oral zinc should be given Specific antimicrobial therapy of diarrheagenic E. coli is problematic 7/18/2015 34 Multiple studies in developing countries,diarrhea genic E. coli strains to be commonly resistant to antibiotics such as TMP-SMX and ampicillin (6070%) There are no randomized controlled studies of antibiotics for the treatment of diarrheagenic E. coli diarrhea in children ETEC respond to antimicrobial agents such as TMP-SMX when the E. coli strains are susceptible. ETEC cases from traveler's diarrhea trials respond to ciprofloxacin, azithromycin In a child who fails to respond to therapy of a dysenteric syndrome in the presence of initially negative stool culture results, additional cultures should be obtained and the child should be re-evaluated for other possible diagnoses 7/18/2015 35 However, other than for a child recently returning from travel in the developing world, empirical treatment of severe watery diarrhea with antibiotics is seldom appropriate EIEC infections may be treated before the availability of culture results because the clinician suspects shigellosis and has begun empirical therapy If the organisms prove to be susceptible, TMP-SMX is an appropriate choice 7/18/2015 36 7/18/2015 37 7/18/2015 38