eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Shigella Infection

Jaya Sureshbabu, MBBS, DCh, MRCPCH(UK), MRCPI(Paeds), MRCPS(Glasg), DCH(Glasg), Registrar, Department of Pediatrics/Neonatology, Mid-Western Regional Hospital, Ireland
Poothirikovil Venugopalan, MBBS, MD, FRCP (Glasg), FRCPCH, Consulting Staff, Department of Child Health, University Hospital of Hartlepool, UK; Walid Abuhammour, MD, FAAP, Associate Professor of Pediatrics, Michigan State University; Director of Pediatric Infectious Disease, Department of Pediatrics, Hurley Medical Center; Ilyas Burny, MD, Staff Physician, Department of Pediatrics, Hurley Medical Center

Updated: Jul 31, 2008

Introduction

Background

Shigella organisms are a group of gram-negative, facultative intracellular pathogens. They were recognized as the etiologic agents of bacillary dysentery or shigellosis in the 1890s. Shigella was adopted as a genus in the 1950s. These organisms are members of the family Enterobacteriaceae and tribe Escherichieae; they are grouped into 4 species: Shigella dysenteriae, Shigella flexneri, Shigella boydii, and Shigella sonnei, also known as groups A, B, C, and D, respectively. They are nonmotile and nonencapsulated. Group A has 13 serotypes, group B has 6 serotypes, group C has 18 serotypes, and group D has 1 serotype.

Geographic distribution and antimicrobial susceptibility varies with different species. S dysenteriae serotype 1 causes deadly epidemics, S boydii is restricted to the Indian subcontinent, and S flexneri and S sonnei are prevalent in developing and developed countries, respectively. S flexneri, an enteroinvasive gram-negative bacteria, is responsible for the worldwide endemic form of bacillary dysentery.

Pathophysiology

Shigella infection is a major public health problem in developing countries where sanitation is poor. Humans are the only natural reservoir. No natural food products harbor endogenous Shigella species, but a wide variety of foods may be contaminated.

Shigellosis is spread by means of fecal-oral transmission. Other modes of transmission include ingestion of contaminated food or water, contact with a contaminated inanimate object, and sexual contact. Vectors like the housefly can spread the disease by physically transporting infected feces.

The infectivity dose (ID) is extremely low. As few as 10 S dysenteriae bacilli can cause clinical disease, whereas 100-200 bacilli are needed for S sonnei or S flexneri infection. The reasons for this low-dose response are not completely clear. One possible explanation is that virulent Shigellae can withstand the low pH of gastric juice.

The incubation period varies from 12 hours to 7 days but is typically 2-4 days; the incubation period is inversely proportional to the load of ingested bacteria.

Bacterial shedding usually ceases within 4 weeks of the onset of illness. A chronic carrier state beyond 1 year is rare.

Virulence

Virulence in Shigella species involves both chromosomal-coded and plasmid-coded genes. Virulent Shigella strains produce disease after invading the intestinal mucosa; the organism only rarely penetrates beyond the mucosa.

The characteristic virulence trait is encoded on a large (220 kb) plasmid responsible for synthesis of polypeptides that cause cytotoxicity. Shigellae that lose the virulence plasmid are no longer pathogenic. Escherichia coli (E coli O157:H7) that harbor this plasmid clinically behave as Shigella bacteria.

Siderophores, a group of plasmid-coded genes, control the acquisition of iron from host cells from its protein-bound state. In the extraintestinal phase of infection by gram-negative bacteria, iron becomes one of the major factors that limits further growth. This limitation occurs because most of the iron in human body is sequestered in hemoproteins (ie, hemoglobin, myoglobin) or iron-chelating proteins involved in iron transport (transferrin and lactoferrin). Many bacteria can secrete iron chelating compounds, or siderophores, which chelate iron from the intestinal fluids and which bacteria then take up to obtain iron for its metabolic needs. These siderophores are under the control of plasmids and are tightly regulated by genes such that, under low iron conditions, expression of the siderophore system is high.

Regulatory genes control expression of virulence genes. Shiga toxin (Stx) is not essential for virulence of S dysenteriae type 1 but contributes to the severity of dysentery. Both plasmid-encoded virulence traits and chromosome-encoded factors are essential for full virulence of shigellae.

Regarding chromosomally encoded enterotoxin, many pathogenic features of Shigella infection are due to the production of potent cytotoxins known as Stx, a potent protein synthesis–inhibiting exotoxin. Shigella strains produce distinct enterotoxins. These are a family of cytotoxins that contain 2 major immunologically non–cross-reactive groups called Stx1 and Stx2. The homology sequences between Stx1 and Stx2 are 55% and 57% in subunits A and B, respectively.

These toxins are lethal to animals; enterotoxic to ligated rabbit intestinal segments; and cytotoxic for vero, HeLa, and some selected endothelial cells (human renal vascular endothelial cells) manifesting as diarrhea, dysentery, and hemolytic-uremic syndrome (HUS). Stx1 is synthesized in significant amount by S dysenteriae serotype 1 and S flexneri 2a and E coli (Shigella toxin–producing E coli [ShET]).

Stx1 and Stx2 are both encoded by a bacteriophage inserted into the chromosome. Stx1 increases inflammatory cytokine production by human macrophages, which, in turn, leads to a burst of interleukin (IL)-8. This could be relevant in recruiting neutrophils to the lamina propria of the intestine in hemorrhagic colitis and accounts for elevated levels of IL-8 in serum of patients with diarrhea-associated HUS.

Stxs have 2 subunits. Subunit A is a 32-kD polypeptide that, when digested by trypsin, generates A1 with a 28-kD fragment and another small fragment, A2, which is 4 kD. A1 fraction acts like N -glycosidase; it removes single adenine residue from 28S rRNA of ribosome and inhibits protein synthesis. The A2 fraction is a pentamer polypeptide of 7.7-kD protein and is required to bind the A1 fraction to the B subunit. The main function of the B subunit is the binding of toxins to the cell surface receptor, typically globotriaosylceramide (Gb3), on the brush border of intestinal epithelial cells.

In summary, events that occur on exposure to Shigella toxin are as follows:

• The B subunit of holotoxin binds to the Gb3 receptor on the cell surface of brush-border cells of the intestines.
• The receptor-holotoxin complex is endocytosed.
• The complex moves to Golgi apparatus and then to the endoplasmic reticulum.

The A1 subunit is released and it targets 28S RNA of the ribosome, inhibiting protein synthesis. Stxs may play a role in the progression of mucosal lesions after colonic cells are invaded, or they may induce vascular damage in the colonic mucosa. Stx adheres to small-intestine receptors and blocks the absorption of electrolytes, glucose, and amino acids from intestinal lumen. The B subunit of Stx binds the host's cell glycolipid in the large intestine and in other cells, such as renal glomerular and tubular epithelia. The A1 domain internalized by means of receptor-mediated endocytosis and causes irreversible inactivation of the 60S ribosomal subunit, inhibiting protein synthesis and causing cell death, microvascular damage to the intestine, apoptosis in renal tubular epithelial cells, and hemorrhage (as blood and mucus in the stool).

Chromosomal genes control lipopolysaccharide (LPS) antigens in cell walls. LPS plays an important role in resistance to nonspecific host defense encountered during tissue invasion. These genes help in invasion, multiplication, and resistance to phagocytosis by tissue macrophages. LPS enhances the cytotoxicity of Stx on human vascular endothelial cells. Shigella chromosomes share most of their genes with E coli K12 strain MG1655, and the diversity of putative virulence genes acquired by means of bacteriophage-mediated lateral gene transfer is extensive. As a result of convergent evolution involving the gain and loss of functions, Shigella species have became highly specific human pathogens with variable epidemiologic and pathologic features.

A 3-kb plasmid that harbors information for the production of bacteriocin by S flexneri strains has been described. The production of this bacteriocin may be related to dysenteric diarrhea these bacterial strains produce.

Intestinal adherence factor

Intestinal adherence factor favors colonization in vivo and in animal models. This is 97-kD outer-membrane protein (OMP) encoded by each gene on chromosomes. This codes for intimin protein, and an anti-intimin response is observed in children with HUS.

Pathology

The host response to primary infection is characterized by the induction of an acute inflammation, which is accompanied by polymorphonuclear cell (PMN) infiltration, resulting in massive destruction of the colonic mucosa. Apoptotic destruction of macrophages in subepithelial tissue allows survival of the invading shigellae, and inflammation facilitates further bacterial entry.

Gross pathology consists of mucosal edema, erythema, friability, superficial ulceration, and focal mucosal hemorrhage involving the rectosigmoid junction primarily.

Microscopic pathology consists of epithelial cell necrosis, goblet cell depletion, PMN infiltrates and mononuclear infiltrates in lamina propria, and crypt abscess formation. Invasion of M cells, the specialized cells that cover the lymphoid follicles of the mucosa, overlying Peyer patches may be the earliest event.

Frequency

United States

The reported incidence of Shigella infections was 2848 cases per 100,000 population in 2007.¹ Most cases are reported during summer months. S sonnei accounts for approximately 78% of all Shigella isolates in recent surveys from the Centers for Disease Control and Prevention (CDC); S flexneri and S boydii account for most of the remainder. S flexneri causes 18% of Shigella infections in the United States. S dysenteriae is rare in the United States. The highest incidence per 100,000 population for shigellosis (27.77 cases) was among children younger than 5 years.

The overall incidence of Shigella infection is 4.67 cases per 100,000 population, and the rate of HUS in pediatric patients younger than 15 years is 0.49 cases per 100,000 population. The estimated annual incidence of Shigella infection did not change significantly in 2007 compared with 2004-2006. More than 95% of Shigella infections may be asymptomatic. Hence, the actual incidence may be 20 times higher than reported.

International

Worldwide, the incidence of shigellosis is estimated to be 164.7 million cases per year, of which 163.2 million were in developing countries, where 1.1 million deaths occurred. About 60% of all episodes and 61% of all deaths attributable to shigellosis involved children younger than 5 years. The incidence in developing countries may be 20 times greater than that in developed countries. Although the relative importance of various serotypes is not known, an estimated 30% of these infections are caused by S dysenteriae.

Case-fatality rates for S dysenteriae infections may approach 30%. Patients with malnutrition are at increased risk of having complicated course. Shigella infection in malnourished children often causes a vicious cycle of further impaired nutrition, recurrent infection, and further growth retardation.

Mortality/Morbidity

Although shigellosis-related mortality is rare in developed countries, S dysenteriae infection is associated with substantial morbidity and mortality rates in the developing world.

• The overall mortality rate in developed countries is less than 1%.
• In the Far East and Middle East, the mortality rates for S dysenteriae infections may be as high as 20-25%.

Race

No racial predilection is known.

Sex

No sexual predilection is known.

Age

According to recent CDC reports, Shigella infection accounted for 28% of all the enteric bacterial infections.¹ Children younger than 5 years had 7% of total reported cases, a rate indicating a disproportionate disease burden in this population.

Clinical

History

• Populations that are at high-risk for shigellosis include the following:
  • Children in daycare centers
  • Orthodox Jews
  • Native Caucasians
  • Persons in custodial institutions
  • International travelers
  • Homosexual men
  • Persons in homes with inadequate water supply
  • People with human immunodeficiency virus (HIV) infection²
• Symptoms include the following:
  • Sudden onset of severe abdominal cramping, high-grade fever, emesis, anorexia, and large-volume watery diarrhea. Seizures may be an early manifestation.
  • Abdominal pain, tenesmus, urgency, fecal incontinence, and small-volume mucoid diarrhea with frank blood (fractional stools) may subsequently occur.
• Signs include the following:
  • Elevated temperatures (as high as 106 º F) are documented in approximately one third of cases, and a generally toxic appearance is noticed.
  • Tachycardia and tachypnea may occur secondary to fever and dehydration. Depending on the degree of dehydration, dry mucous membranes, hypotension, prolonged capillary refill time, and poor skin turgor may be present.
  • Abdominal tenderness is usually central and lower, although it may be generalized.
• Extraintestinal manifestations are as follows:
  • CNS symptoms include severe headache, lethargy, meningismus, delirium, and convulsions lasting less than 15 minutes, especially with S dysenteriae.³ Severe toxic encephalopathy is rare, but lethal complications occur when initial symptoms are followed by sensory obtundation, seizures, coma, and death in 6-48 hours. The pathogenesis of neurologic manifestations during shigellosis is unclear. However, data now clearly demonstrate that Stx is not responsible.
  • Regarding HUS, microangiopathic hemolytic anemia, thrombocytopenia, and renal failure have been reported with S dysenteriae because of vasculopathy mediated by Stx. The principal organ affected in Stx1-mediated HUS is the kidney. This is presumed to be the consequence of the high renal blood flow and abundant baseline expression and high inducibility of the Stx glycolipid receptor Gb_e in the glomerular microcirculation. Manifestations of the disease arise due to 2 primary pathogenetic mechanisms: direct Stx-mediated injury to vascular endothelial cells that leads to tissue ischemia and dysfunction and a systemic inflammatory response triggered by Stx-mediated release of a wide range of cytokines and chemokines, including IL-6, IL-8, and tumor necrosis factor-alpha.
  • Septicemia is rare, except in malnourished children with S dysenteriae infection. Septicemia is sometimes caused by other gram-negative organisms and is related to loss of mucosal integrity by Shigella infection.
  • Profound dehydration and hypoglycemia is more common with S dysenteriae infection.
  • Shigella sepsis may be complicated with disseminated intravascular coagulation (DIC), bronchopneumonia, and multiple organ failure in lethal cases.
  • Arthritis, urethritis, conjunctivitis syndrome is commonly observed in adults carrying human leukocyte antigen (HLA)-B27 histocompatibility antigen.
  • Cholestatic hepatitis, if present, is usually mild.
  • Myocarditis is identified with cardiogenic shock, arrhythmias, and heart block.
  • Rectal prolapse, toxic megacolon, and intestinal obstruction may be present.
  • Shigellosis in the first 6 months of life is rare probably due to presence of antibodies to both virulence plasmid-coded antigens and lipopolysaccharides in the breast milk. Shigellosis in the neonatal period results from mother-to-infant fecal-oral transmission during labor and delivery, usually from asymptomatic mothers.
  • Symptoms usually begin on the third day of life.
  • Septicemia and chronic diarrhea are common.
  • Fever may be absent.
  • Diarrhea is not usually bloody.
  • Intestinal perforation and mortality are more common in this group than in older children.
• Shigellosis in patients with HIV infection is often a protracted, chronic, relapsing disease (even when treated with antibiotics). Bacteremia may be a complication.

Physical

• Physical examination during acute illness reveals a febrile ill-appearing child. Fever with a temperature as high as 39-40 º C may be noted.
• The patient's hydration status should be carefully assessed. Especially note dryness of the oral mucosa, lack of tears, decreased urine output, and loss of skin turgor.
• Abdominal examination may reveal generalized mild-to-moderate tenderness with no guarding or rigidity.
• In a child who presents with febrile seizures, careful neurologic examination is mandatory to exclude meningitis.

Causes

• Shigella infection is spread by means of fecal-oral transmission.

Differential Diagnoses

Campylobacter Infections
Crohn Disease
Escherichia Coli Infections
Salmonella Infection
Ulcerative Colitis
Yersinia Enterocolitica Infection

Other Problems to Be Considered

Clostridium difficile infection
Entameba histolytica infection

Workup

Laboratory Studies

• Hematology
  • The total WBC count reveals no consistent findings. A shift to the left  (increased number of band cells) in the differential WBC count in a patient with diarrhea suggests bacillary dysentery. Leukopenia or leukemoid reactions are occasionally detected.
  • In HUS, anemia and thrombocytopenia occur.
  • Bacteremia is rare, even in severe disease, possibly due to the superficial nature of Shigella infection; the organism rarely penetrates beyond the mucosa.
• Stool examination
  • Routine microscopy may reveal sheets of PMNs. Platelet counts are reduced.
  • In approximately 70% of patients with shigellosis, fecal blood or leukocytes (confirming colitis) are detectable in the stool. Fecal blood and leukocytes are present in 50% of patients.
• Stool culture
  • A sample for stool culture should be obtained in all suspected cases of shigellosis.
  • The yield from stool cultures is greatest early in the course of disease. Guidelines for obtaining specimens to improve the yield are as follows:
    • Process specimens immediately after collection.
    • If processing is delayed, use a transport medium (eg, buffered glycerol saline).
    • Collect more than one stool or rectal (not anal) swab and inoculate them promptly on at least 2 different culture media.
    • Specimens should be plated lightly onto MacConkey, xylose-lysine-deoxycholate, Hektoen enteric, or Salmonella-Shigella, or eosin-methylene blue agars.
  • If processing is delayed, a rectal-swab sample can be placed in Cary-Blair transport medium or buffered glycerol saline.
  • After overnight incubation, colorless, nonlactose-fermenting colonies may be tested by means of latex agglutination to establish a preliminary identification of Shigella infection.
  • Antimicrobial susceptibility tests of all confirmed isolates should be performed by using the agar diffusion technique. The agar and broth-dilution methods are also widely used. The new Epsilometer strip method (E test) is used to accurately determine the minimum inhibitory concentration (MIC).
  • Despite meticulous care in obtaining and processing specimens from patients infected with Shigella species, approximately 20% may fail to yield Shigella organisms.
• Enzyme immunoassay: An enzyme immunoassay for Stx is used to detect S dysenteriae type 1 in the stool.
• Rapid techniques: With rapid techniques, gene probes or polymerase chain reaction (PCR) primers are directed toward virulence genes (invasion plasmid locus).

Other Tests

• Additional diagnostic tools, such as gene probes, are being developed.

Treatment

Medical Care

The clinician should rapidly assess the patient's fluid and electrolyte status and institute parenteral or oral hydration along with antipyretics as needed. Prompt recognition and treatment of seizures and raised intracranial pressure are essential. Nutritional supplementation of vitamin A (200,000 IU) can hasten clinical resolution in malnourished children.

Surgical Care

Surgical care may be required for complications (eg, intestinal perforation).

Consultations

• Consult a neurologist if seizures and altered sensorium predominate.
• Consult a nephrologist if HUS is suspected (eg, for patients with anemia, thrombocytopenia, oliguria, and renal failure).

Diet

The diet may need to be restricted according to the severity of the disease.

Activity

No restrictions are necessary.

Medication

Various antimicrobial agents are effective in the treatment of shigellosis, although options are becoming limited because of globally emerging drug resistance. Resistance of Shigella species to sulfonamides, tetracyclines, ampicillin, and trimethoprim-sulfamethoxazole (TMP-SMX) has been reported worldwide, and these agents are not recommended as empirical therapy. Most clinical infections with S sonnei are self-limited (48-72 h) and may not require antimicrobial therapy.

Because shigellosis is self-limiting, some authorities recommend withholding antibiotic therapy. However, even if not fatal, the untreated illness may cause chronic or recurrent diarrhea, making a child quite ill for several weeks; this may lead to malnutrition, especially in developing countries. The risk of continued shedding of organisms in stool increases the risk of transmission of further disease among contacts argues against withholding antimicrobial treatment.

Presently, no US Food and Drug Administration (FDA)–approved vaccines are available.

Antimicrobial therapy is typically administered for 5 days. Antibiotic treatment decreases the duration of illness, person-to-person spread, and cases in household contacts. Treatment in malnourished children (eg, in developing countries) is likely to reduce the risk of worsening malnutrition morbidity after shigellosis. In persons infected with S dysenteriae type 1, early administration of effective antibiotics is decreases Stx concentrations in the stool and lowers the risk of HUS. However, the risk of HUS caused by E coli O157-H7 may be increased with the early administration of antibiotics. Prophylactic antibiotics are not recommended for contacts.

Antidiarrheal medications (diphenoxylate hydrochloride with atropine [Lomotil] or loperamide) should not be used because of the risk of prolonging the illness.

A child with typical dysentery that responds to initial empirical antibiotic treatment should continue taking the same drug for a full 5-day course, even if the stool culture is negative.

Nutritional supplementation including vitamin A (200,000 IU) and zinc (20 mg/d for 14 d)⁴ may be administered to hasten the clinical recovery and immune response in the settings of malnutrition or in certain geographic areas.

Antibiotics

Ampicillin and TMP-SMZ are effective for susceptible strains; amoxicillin is less effective than this because of its rapid absorption high in the GI tract. The oral route is preferred except for seriously ill patients. In the United States, sentinel surveillance data from 1999-2000 indicated that 54% of S sonnei and 47% of S flexneri organisms were resistant to ampicillin and TMP-SMZ. Ampicillin (but not amoxicillin) is still the drug of choice if the isolate is susceptible to this drug.

If ampicillin and TMP-SMZ resistant strain is isolated or if susceptibility is unknown, parenteral ceftriaxone sodium, a fluoroquinolone (eg, ciprofloxacin, ofloxacin), or azithromycin dihydrate are the drugs of choice. Fluoroquinolones are typically not administered to children and adolescents younger than 18 years unless other antibiotic choices are not suitable.

Trimethoprim and sulfamethoxazole (Bactrim, Cotrim)

Combination effective for shigellosis. Produces sequential blockade in folic acid synthesis. Effect frequently synergistic and bactericidal.

Dosing

Adult

>40 kg: 160 mg/dose PO bid (based on TMP component)

Pediatric

<2 months: Contraindicated
>2 months: 8-10 mg/kg/d PO divided bid for 5 d (based on TMP dose)

Interactions

May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Contraindications

Documented hypersensitivity; megaloblastic anemia caused by folate deficiency; glucose-6-phosphate dehydrogenase (G-6-PD) deficiency; age <2 mo; last trimester of pregnancy (due to potential toxicity to newborn, eg, jaundice, hemolytic anemia, kernicterus)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue at first appearance of rash or sign of adverse reaction; caution in patients with renal and/or hepatic dysfunction; maintain adequate fluid intake to prevent crystalluria and renal stone formation

Ampicillin (Principen)

Broad-spectrum penicillin. Interferes with bacterial cell-wall synthesis during active replication, causing bactericidal activity against susceptible organisms.

Dosing

Adult

250-500 mg PO q6h

Pediatric

50-100 mg/kg/d PO divided q4-6h; not to exceed 3 g/d

Interactions

Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin-related rash; may decrease effects of PO contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Ceftriaxone (Rocephin)

Third-generation cephalosporin. Blocks transpeptidase activity of penicillin-binding proteins (PBP). Used in patients with contraindications to TMP-SMZ.

Dosing

Adult

2 g IV/IM as a single dose or in 2 divided doses

Pediatric

50 mg/kg/d IV/IM as a single daily dose for empiric treatment; continue for 5 d for treatment regimen

Interactions

Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

History of penicillin allergy; rashes; thrombophlebitis; GI upset with nausea, vomiting, and diarrhea

Azithromycin (Zithromax)

Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis not affected. Concentrates in phagocytes and fibroblasts, as demonstrated with in vitro incubation techniques. In vivo data suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues. Used to treat mild-to-moderate microbial infections.

Dosing

Adult

Day 1: 500 mg PO
Days 2-5: 250 mg PO qd

Pediatric

Day 1: 12 mg/kg PO as a single dose
Days 2-5: 6 mg/kg PO qd

Interactions

May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine

Contraindications

Documented hypersensitivity; hepatic impairment; do not administer with pimozide

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May increase hepatic enzyme levels and cause cholestatic jaundice; caution in impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Nalidixic acid (NegGram)

First-generation quinolone. Blocks bacterial DNA gyrase. Useful in patients with sulfas and cephalosporin allergy.

Dosing

Adult

1 g PO q6h

Pediatric

55 mg/kg/d PO in 4 divided doses for 5 d

Interactions

Potentiates warfarin effect; antacids decrease absorption

Contraindications

Documented hypersensitivity, convulsive disorders, infants <3 months

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with impaired renal and hepatic function, G-6-PD deficiency; may cause gastrointestinal intolerance, rashes, photosensitivity; cartilage degeneration (animals)

Follow-up

Deterrence/Prevention

• For individuals who travel to highly endemic areas, recommend that all fruits and vegetables be washed, peeled, and cooked (see the CDC Web site).
• In developed countries, person-to-person transmission is the most common source of infection. In developing countries, water contaminated with human waste is the most common source for infection.
• Encourage prolonged breastfeeding in infants because the incidence of disease is markedly decreased in breastfed babies.
• The following measures help prevent person-to-person transmission of Shigella species:
  • Education of families and child-care centre personnel in handwashing techniques, especially after toilet use
  • Avoidance of food preparation by personnel who change diapers in daycare centers
  • Exclusion of febrile children with diarrhea from daycare centers
  • Proper handling and refrigeration of food, even after cooking
  • Use of universal precautions and isolation of persons with diarrhea in institutions and hospitals
  • Exclusion of children with documented Shigella gastroenteritis from daycare centers until 2 stool culture findings are negative

Complications

• Dehydration is the most common complication of shigellosis.
• Other reported complications include the following:
  • CNS complications
    • Seizures were previously thought to be caused by the elaboration of Stx. The etiology is presently uncertain.
    • Syndrome of inappropriate secretion of antidiuretic hormone with profound hyponatremia may occur.
    • Lethargy, meningismus, delirium, seizures, and hypoglycemia may be observed.
    • Encephalopathy and meningitis are rare and may be lethal.
  • HUS associated with strains that produce Stx (eg, S dysenteriae serotype 1 and S flexneri 2a)
  • Septicemia and DIC, particularly in malnourished children
  • Arthritis
    • Postinfectious arthritis is a late complication of S flexneri infection, especially in persons with HLA-B27 marker.
    • Arthritis, conjunctivitis, urethritis syndrome is most common in adults with HLA-B27 marker (occurs 2-5 wk after enteritis).
  • GI complications
    • Cholestatic hepatitis
    • Rectal prolase
    • Toxic megacolon
    • Pseudomembranous colitis
    • Protein-losing enteropathy
  • Other manifestations
    • Conjunctivitis, iritis, corneal ulcers, cystitis, myocarditis, and vaginitis are uncommon.
    • Ekiri syndrome is a rare syndrome that consists of extreme toxicity, seizures, hyperpyrexia, and headache; it can be rapidly fatal due to brain edema.

Prognosis

• Most patients recover even without treatment, although illness is more prolonged and more severe if not treated.
  • The fever usually lessens within 24 hours.
  • Frequency of stool deceases within 2-3 days.
• The overall mortality rate in developed countries is less than 1%. In the Far East and Middle East, the mortality rates for infections of S dysenteriae may be as high as 20-25%.
• Severely malnourished children with shigellosis and hypoglycemia, hypothermia, altered consciousness, and/or bronchopneumonia are at high risk of dying.

Miscellaneous

Medicolegal Pitfalls

• Shigella infections may be misdiagnosed as meningitis or meningoencephalitis.
• Shigella infection may be misdiagnosed or not confirmed if specimens are not processed without delay and selective media are not used for culture. More than one stool culture or rectal swab should be obtained and promptly inoculated onto more than one type of culture medium.

References

1. CDC. Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food--10 states, 2007. MMWR Morb Mortal Wkly Rep. Apr 11 2008;57(14):366-70. [Medline]. [Full Text].

2. Baer JT, Vugia DJ, Reingold AL, et al. HIV infection as a risk factor for shigellosis. Emerg Infect Dis. Nov-Dec 1999;5(6):820-3. [Medline].

3. Khan WA, Dhar U, Salam MA, et al. Central nervous system manifestations of childhood shigellosis: prevalence, risk factors, and outcome. Pediatrics. Feb 1999;103(2):E18. [Medline].

4. Rahman MJ, Sarkar P, Roy SK. Effect of zinc supplementation as adjunct therapy on the systemic immune response in shigellosis. Am J Clin Nutr. Feb, 2005;81(2):495-502. [Medline].

5. Basualdo W, Arbo A. Randomized comparison of azithromycin versus cefixime for treatment of shigellosis in children. Pediatr Infect Dis J. Apr 2003;22(4):374-7. [Medline].

6. Bennish ML, Khan WA, Begum M, et al. Low risk of hemolytic uremic syndrome after early effective antimicrobial therapy for Shigella dysenteriae type 1 infection in Bangladesh. Clin Infect Dis. Feb 1 2006;42(3):356-62. [Medline].

7. Edwards BH. Salmonella and Shigella species. Clin Lab Med. Sep 1999;19(3):469-87, v. [Medline].

8. Friedrich AW, Bielaszewska M, Zhang WL, et al. Escherichia coli harboring Shiga toxin 2 gene variants: frequency and association with clinical symptoms. J Infect Dis. Jan 1 2002;185(1):74-84. [Medline].

9. Gomez HF, Cleary TG. Shigella species. In: Principles and Practice of Pediatric Infectious Diseases. New York, NY: Churchill Livingstone; 1997:429-34.

10. Gomez HF, Cleary TG. Shigella. In: Textbook of Pediatric Infectious Diseases. Philadelphia, PA: WB Saunders; 1998:1207-317.

11. Huicho L, Sanchez D, Contreras M, et al. Occult blood and fecal leukocytes as screening tests in childhood infectious diarrhea: an old problem revisited. Pediatr Infect Dis J. Jun 1993;12(6):474-7. [Medline].

12. Ingersoll MA, Zychlinsky A. ShiA abrogates the innate T-cell response to Shigella flexneri infection. Infect Immun. Apr 2006;74(4):2317-27. [Medline].

13. Katz DE, Coster TS, Wolf MK, et al. Two studies evaluating the safety and immunogenicity of a live, attenuated Shigella flexneri 2a vaccine (SC602) and excretion of vaccine organisms in North American volunteers. Infect Immun. Feb 2004;72(2):923-30. [Medline].

14. Keusch GT, Jacewicz M, Acheson DW, et al. Globotriaosylceramide, Gb3, is an alternative functional receptor for Shiga-like toxin 2e. Infect Immun. Mar 1995;63(3):1138-41. [Medline].

15. Mitra AK, Alvarez JO, Wahed MA, et al. Predictors of serum retinol in children with shigellosis. Am J Clin Nutr. Nov 1998;68(5):1088-94. [Medline].

16. Nataro JP. Treatment of bacterial enteritis. Pediatr Infect Dis J. May 1998;17(5):420-1. [Medline].

17. Nathoo KJ, Porteous JE, Siziya S, et al. Predictors of mortality in children hospitalized with dysentery in Harare, Zimbabwe. Cent Afr J Med. Nov 1998;44(11):272-6. [Medline].

18. Navia MM, Gascon J, Vila J. Analysis of the mechanisms of resistance to several antimicrobial agents in Shigella spp. causing travellers' diarrhoea. Clin Microbiol Infect. Dec 2005;11(12):1044-7. [Medline].

19. Niyogi SK. Shigellosis. J Microbiol. Apr 2005;43(2):133-43. [Medline].

20. Oaks EV, Turbyfill KR. Development and evaluation of a Shigella flexneri 2a and S. sonnei bivalent invasin complex (Invaplex) vaccine. Vaccine. Mar 20 2006;24(13):2290-301. [Medline].

21. Ochoa TJ, Cleary TG. Shigella. In: Kliegman, Behrman, Jenson, Stanton, eds. Nelson Textbook of Paediatrics. 18^th ed. Philadelphia, PA: Saunders Elsevier; 2007:1191-3.

22. Pazhani GP, Ramamurthy T, Mitra U, et al. Species diversity and antimicrobial resistance of Shigella spp. isolated between 2001 and 2004 from hospitalized children with diarrhoea in Kolkata (Calcutta), India. Epidemiol Infect. Dec 2005;133(6):1089-95. [Medline].

23. Plotz FB, Arets HG, Fleer A, et al. Lethal encephalopathy complicating childhood shigellosis. Eur J Pediatr. Jul 1999;158(7):550-2. [Medline].

24. Richardson SE, Rotman TA, Jay V, et al. Experimental verocytotoxemia in rabbits. Infect Immun. Oct 1992;60(10):4154-67. [Medline].

25. Tzipori S, Sheoran A, Akiyoshi D, et al. Antibody therapy in the management of shiga toxin-induced hemolytic uremic syndrome. Clin Microbiol Rev. Oct 2004;17(4):926-41, table of contents. [Medline].

26. Wong CS, Jelacic S, Habeeb RL, et al. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med. Jun 29 2000;342(26):1930-6. [Medline].

27. Yang F, Yang J, Zhang X, et al. Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery. Nucleic Acids Res. 2005;33(19):6445-58. [Medline].

Keywords

Shigella infection, shigellosis, Shigella dysenteriae, S dysenteriae, Shigella dysenteriae, S dysenteriae, Shigella sonnei, S sonnei, Shigella flexneri, S flexneri, Shigella boydii, S boydii, infectivity dose, ID, Shiga toxin, Stx, bacillary dysentery, Escherichia coli, diarrhea, hemolytic-uremic syndrome, dehydration, hypotension, abdominal tenderness, microangiopathic hemolytic anemia, thrombocytopenia, renal failure, septicemia, hypoglycemia, bronchopneumonia, disseminated intravascular coagulation, DIC, cholestatic hepatitis, arthritis, conjunctivitis, urethritis, myocarditis, rectal prolapse, cardiogenic shock, arrhythmias, heart block, bacteremia, rectal prolapse, toxic megacolon

Contributor Information and Disclosures

Author

Jaya Sureshbabu, MBBS, DCh, MRCPCH(UK), MRCPI(Paeds), MRCPS(Glasg), DCH(Glasg), Registrar, Department of Pediatrics/Neonatology, Mid-Western Regional Hospital, Ireland
Jaya Sureshbabu, MBBS, DCh, MRCPCH(UK), MRCPI(Paeds), MRCPS(Glasg), DCH(Glasg) is a member of the following medical societies: Royal College of Paediatrics and Child Health, Royal College of Physicians and Surgeons of Glasgow, and Royal College of Physicians of Ireland
Disclosure: Nothing to disclose.

Coauthor(s)

Poothirikovil Venugopalan, MBBS, MD, FRCP (Glasg), FRCPCH, Consulting Staff, Department of Child Health, University Hospital of Hartlepool, UK
Poothirikovil Venugopalan, MBBS, MD, FRCP (Glasg), FRCPCH is a member of the following medical societies: British Cardiac Society, Royal College of Paediatrics and Child Health, and Royal College of Physicians and Surgeons of Glasgow
Disclosure: Nothing to disclose.

Walid Abuhammour, MD, FAAP, Associate Professor of Pediatrics, Michigan State University; Director of Pediatric Infectious Disease, Department of Pediatrics, Hurley Medical Center
Walid Abuhammour, MD, FAAP is a member of the following medical societies: American Medical Association and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Ilyas Burny, MD, Staff Physician, Department of Pediatrics, Hurley Medical Center
Ilyas Burny, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

Glenn J Fennelly, MD, MPH, Director, Division of Pediatric Infectious Diseases, Jacobi Medical Center; Associate Professor, Department of Pediatrics, Albert Einstein College of Medicine
Glenn J Fennelly, MD, MPH is a member of the following medical societies: Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)