Yersinia Enterocolitica

Yersinia enterocolitica is a pleomorphic, gram-negative cocobacillus that belongs to the family Enterobacteriales. As a human pathogen, Y enterocolitica most frequently is associated with enterocolitis, acute diarrhea, terminal ileitis, mesenteric lymphadenitis, and pseudoappendicitis,[1] with the spectrum of disease ranging from asymptomatic to life-threatening sepsis, especially in infants. The bacterium was first reported by Mclver and Picke, in 1934.[7] Schleifstein and Coleman provided the first recognized description of 5 human isolates of Y enterocolitica, in 1939. (See Prognosis and Clinical Presentation.)[8]

In several countries, Y enterocolitica has eclipsed Shigella species and approaches Salmonella and Campylobacter species as the predominant cause of acute bacterial gastroenteritis. Y enterocolitica most commonly affects young individuals (approximately 75% of patients with Y enterocolitica infection are aged 5-15 years), but whether this represents an increased susceptibility or a greater likelihood of developing symptomatic illness is unclear. Most cases of Y enterocolitica infection are sporadic, but reports have documented large outbreaks centered on a single contaminated source. (See Epidemiology.)

Human yersiniosis is attributed to contaminated pork, milk, water, and tofu consumption, as well as to blood transfusion. Infected individuals may shed Y enterocolitica in stools for up to 90 days after the symptom resolution, suggesting that early detection of Y enterocolitica from diarrheal stool samples is critical in preventing its transmission and an eventual outbreak. (See Pathophysiology, Etiology, Clinical Presentation, and Workup.)[9, 10]

Classification

Y enterocolitica is classified according to various distinct biochemical and serologic reactions. Based on biochemical characteristics, 6 biotypes of the bacterium have been described. Biotypes 2, 3, and 4 are most common in humans. The serotyping is based on O and H antigens. More than 60 serotypes of Y enterocolitica have been described. The serotypes most clearly pathogenic to humans include O:3, O:5,27, O:8, O:9, and O:13.

H-antigen typing can be a valuable supplement to O-antigen typing and biochemical characterization in epidemiologic investigations. Accurate identification of pathogenic strains requires consideration of both the biotype and the serotype because some strains can contain multiple cross-reacting O antigens.

Metabolism

Y enterocolitica is non–lactose-fermenting, glucose-fermenting, and oxidase-negative facultative anaerobe that is motile at 25°C and nonmotile at 37°C. Most, but not all, Y enterocolitica isolates reduce nitrates. The presence of bile salts in the medium prevents the organism from fermenting lactose. Colonies of Y enterocolitica do not produce hydrogen sulfide in triple sugar iron medium, but the organism is urease positive.

Patient education

Educate patients and individuals at risk for infection about appropriate hygiene methods and signs or symptoms of infection. Encourage public awareness of outbreaks, modes of transmission, and ways to prevent transmission.

As with other members of the genus Yersinia, Y enterocolitica is an invasive organism that appears to cause disease by tissue destruction. Researchers have elucidated several potential pathogenic properties, including chromosomally mediated effects (eg, attachment to tissue culture, production of enterotoxin) and plasmid-mediated mechanisms (eg, production of Vw antigens, calcium dependency for growth, autoagglutination).

Invasion and colonization

Invasion of human epithelial cells and penetration of the mucosa occurs in the ileum, followed by multiplication in Peyer patches. A 103-kd protein, known as invasin and determined by the INV gene, mediates bacterial invasion. The best-defined pathway is through the action of invasin.[11]

As a foodborne pathogen, Y enterocolitica can efficiently colonize and induce disease in the small intestine. Following ingestion, the bacteria colonize the lumen and invade the epithelial lining of the small intestine, resulting in the colonization of the underlying lymphoid tissues known as Peyer patches. A direct lymphatic link between the Peyer patches and mesenteric lymph nodes may result in bacterial dissemination to these sites, resulting in mesenteric lymphadenitis or systemic infection.

Dissemination to extraintestinal sites, such as the spleen, is hypothesized to occur via 2 main mechanisms: (1) colonization of the Peyer patches, which then can be used as a staging ground for spread into the blood and/or lymph, ultimately resulting in the appearance of bacteria in other tissues, and (2) bypass of the Peyer patches, with Y enterocolitica going straight to systemic colonization. The possibilities of additional avenues for dissemination have yet to be excluded.

Y enterocolitica colonization of the intestinal lymphoid tissues requires transmigration of the bacteria from the intestinal lumen across an epithelial tissue barrier. Antigen-sampling intestinal epithelial cells known as M cells are thought to be critical for this transmigratory process. The epithelium overlying the Peyer patches has a high concentration of M cells (although these cells also have been identified throughout the non–Peyer patch areas of the small intestine).

Y enterocolitica and the related pathogen Y pseudotuberculosis produce at least 3 invasion proteins, Ail, YadA, and the aforementioned invasin, which potentially could promote adherence to and invasion of M cells. Invasin, the principle invasion factor of Y enterocolitica and Y pseudotuberculosis, binds to ß1 -chain integrin receptors with high affinity, promoting internalization. These receptors are found at high levels on the luminal side of M cells but not on the luminal side of enterocytes.[12]

Enterotoxicity

The enterotoxin produced by Y enterocolitica is similar to that produced by the heat-stable Escherichia coli; however, it likely plays a minor role in causing disease, as diarrheal syndromes have been observed in the absence of enterotoxin production. In addition, the toxin does not appear to be produced at temperatures higher than 30°C. The plasmid-mediated outer membrane antigens are associated with bacterial resistance to opsonization and neutrophil phagocytosis.

Iron and pathogenicity

One unique property of Y enterocolitica is its inability to chelate iron, which is an essential growth factor for most bacteria and is obtained through the production of chelators known as siderophores. Y enterocolitica does not produce siderophores but can utilize siderophores produced by other bacteria (eg, desferrioxamine E produced by Streptomyces pilosus).

Iron overload substantially increases the pathogenicity of Y enterocolitica, perhaps through attenuation of the bactericidal activity of the serum. Researchers observe differences in the iron requirements of different serotypes of the organism; such differences may explain, in part, the varying degrees of virulence among serotypes.

Complications

After an incubation period of 4-7 days, infection may result in mucosal ulceration (usually in the terminal ileum and rarely in the ascending colon), necrotic lesions in Peyer patches, and mesenteric lymph node enlargement. See the image below.

In severe cases, bowel necrosis may occur, as a result of mesenteric vessel thrombosis.[13] Focal abscesses may occur. In persons with human leukocyte antigen (HLA)–B27, reactive arthritis is not uncommon, possibly because of the molecular similarity between HLA-B27 antigen and Yersinia antigens. The pathogenesis of Yersinia -associated erythema nodosum is unknown.[14, 15]

Human clinical Y enterocolitica infections ensue after ingestion of the microorganisms in contaminated food or water or by direct inoculation through blood transfusion.

Y enterocolitica potentially is transmitted by contaminated unpasteurized milk and milk products, raw pork, tofu, meats, oysters, and fish.[16, 17] Outbreaks have been associated with raw vegetables; the surface of vegetables can become contaminated with pathogenic microorganisms through contact with soil, irrigation water, fertilizers, equipment, humans, and animals.

Pasteurized milk and dairy products also can cause outbreaks because Yersinia can proliferate at refrigerated temperatures.[18, 19]

Animal reservoirs of Y enterocolitica include swine (principle reservoir), dogs, cats, cows, sheep, goats, rodents, foxes, porcupines, and birds.

Reports of person-to-person spread are conflicting and generally are not observed in large outbreaks. Transmission via blood products has occurred, however, and infection can be transmitted from mother to newborn infant. Fecal-oral transmission among humans has not been proven.[20, 21]

Underlying hemochromatosis or hemoglobinopathies are associated with relative risk of Y enterocolitica infection.[6]

Occurrence in the United States

As of an October 26, 2016 review CDC estimates Y enterocolitica causes almost 117,000 illnesses, 640 hospitalizations, and 35 deaths in the United States every year.

The incidence of yersiniosis in FoodNet sites in 2014 was 0.28 cases per 100,000 population.

For 2010, the CDC’s Foodborne Diseases Active Surveillance Network (FoodNet), using surveillance data from 10 US sites, preliminarily identified a total of 19,089 laboratory-confirmed cases of infection caused by bacterial pathogens that are commonly transmitted through food. Cases and incidence per 100,000 population were reported as follows[22] :

• Salmonella (8256; 17.6)

• Campylobacter (6365; 13.6)

• Shigella (1780; 3.8)

• Shiga toxin-producing E coli (STEC) non-O157 (451; 1.0)

• STEC O157 (442; 0.9)

• Vibrio (193; 0.4)

• Yersinia (159; 0.3)

• Listeria (125; 0.3)

In the United States, Yersinia enterocolitica accounts for approximately 5% of bacterial enteric infections among children younger than 5 years, according to a 2012 study by Scallan et al. The investigators found this to be a greater incidence than that for the enterohemorrhagic E coli strain O157 (3%), but a lower incidence than those for nontyphoidal Salmonella (42%), Campylobacter (28%), and Shigella (21%).[23]

Scallan et al estimated that the 5 pathogens together cause more than 290,000 illnesses annually in children under 5 years.

Y enterocolitica infection is more common in cooler climates, and its prevalence peaks from November to January.[24]

International statistics

Y enterocolitica has been isolated in patients in many countries worldwide, but the infection appears to occur predominantly in cooler climates, being much more common in northern Europe, Scandinavia, and Japan. Most isolates reported from Canada and Europe are O:3 and O:9 serotypes.[25] The O:3 serotype also is common in Japan. Isolation of Y enterocolitica in developing countries is uncommon.[26]

Race- and age-related demographics

Higher incidence of Y enterocolitica infection has been observed among Black infants in the United States.[27]

Reports document symptomatic Y enterocolitica infection most commonly in younger age groups. A sample collection from 1988-1991 showed that 77.6% of infections occurred in children aged 12 months and younger, making Y enterocolitica the second most common cause of bacterial gastrointestinal infection in children.[23, 28, 29]

Clinical manifestations of Y enterocolitica infection exhibit some age-dependent predilections, with reactive arthritis and erythema nodosum being more common in older patients. Older patients with more debility are more likely to develop bacteremia than are younger, healthier patients.

Yersiniosis usually is either self-limited or is responsive to therapy; however, reinfection is possible. Most patients with Y enterocolitica infection are symptomatic; however, asymptomatic carriage may occur. Death is uncommon, but patients with significant comorbidities are at risk for Y enterocolitica bacteremia, which carries a case fatality rate of 34-50%.

A national, registry-based study of 52,121 patients in Denmark reported estimates for the risk for severe, hospitalization-requiring complications and long-term sequelae up to 1 year after infection with 5 common bacterial gastrointestinal pathogens. Of the 3922 cases of Y enterocolitica infection reported, 368 required hospitalization.[30]

A report from the CDC stated that in 2010 (preliminary data), of 159 Yersinia infections in the United States, 52 required hospitalization and 1 resulted in death.[22]

Various manifestations of Y enterocolitica infection have been reported, including the following[31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43] :

• Enterocolitis

• Pseudoappendicitis

• Mesenteric adenitis

• Reactive arthritis - Can last 1-4 months

• Erythema nodosum

• Septicemia

• Pharyngitis

• Dermatitis

• Myocarditis

• Glomerulonephritis

• Hemolytic anemia

• Intestinal perforation

Iron is an essential growth factor for the organism, and iron overload (eg, chronic hemolysis, hereditary hemochromatosis) is associated with an increased risk of systemic disease. Deferoxamine therapy also increases susceptibility to Y enterocolitica disease.

The usual presentation of Y enterocolitica infection includes diarrhea (the most common clinical manifestation of this infection), low-grade fever, and abdominal pain lasting 1-3 weeks. Diarrhea may be bloody in severe cases. Vomiting is present in approximately 15-40% of cases.

The existence of extraintestinal symptoms after a gastrointestinal illness also may indicate the possibility of yersiniosis.

Enterocolitis

Enterocolitis, the most common presentation of Y enterocolitica, occurs primarily in young children, with a mean age of 24 months. The incubation period is 4-6 days, typically with a range of 1-14 days.

Prodromal symptoms of listlessness, anorexia, and headache may be present. Such symptoms are followed by watery, mucoid diarrhea (78-96%); fever (43-47%); colicky abdominal pain (22-84%); bloody stools (< 10%); and white blood cells (WBCs) in the stool (25%). The diarrhea generally has a duration of 1 day to 3 weeks.

Most cases are self-limited. However, concomitant bacteremia may occur in 20-30% of infants younger than 3 months.

Complications of enterocolitis include appendicitis,[42] diffuse ulceration and inflammation of the small intestine and colon, peritonitis,[44, 45] meningitis, intussusception,[46] and cholangitis.

Mesenteric adenitis, mesenteric ileitis, and acute pseudoappendicitis

These manifestations are characterized by the following symptoms (although nausea, vomiting, diarrhea, and aphthous ulcers of the mouth also can occur):

• Fever

• Abdominal pain

• Tenderness of the right lower quadrant

• Leukocytosis

Pseudoappendicitis syndrome is more common in older children and young adults.[47] Patients with Y enterocolitica infection often undergo appendectomy; several Scandinavian studies suggested a prevalence rate of 3.8-5.6% for infection with Y enterocolitica in patients with suspected appendicitis.

Analysis of several common-source outbreaks in the United States found that 10% of 444 patients with symptomatic, undiagnosed Y enterocolitica infection underwent laparotomy for suspected appendicitis.

Reactive arthritis

This is associated with HLA-B27 (found in approximately 80% of affected patients). Most commonly reported in Scandinavia, polyarticular arthritis can occur after Y enterocolitica infection. Joint symptoms, which occur in approximately 2% of patients, typically arise 1-2 weeks after gastrointestinal illness.[15]

The large joints of the lower extremities are involved most commonly, and symptoms usually persist for 1-4 months, although reports document prolonged syndromes.

Myocarditis and glomerulonephritis

These are other postinfection sequelae associated with the HLA-B27.[48]

Erythema nodosum

This manifests as painful, raised red or purple lesions, mainly on the patient’s legs and trunk. Lesions appear 2-20 days after the onset of fever and abdominal pain and resolve spontaneously in most cases in about a month. The female-to-male ratio of erythema nodosum is 2:1, and it is more common in adults than in children.

Septicemia

In this, a bacteremic spread to extraintestinal sites occurs, resulting in critical illness. Y enterocolitica septicemia is reported most commonly in patients who have predisposing conditions, including alcoholism, diabetes mellitus, or an underlying immune defect.

Patients with iron overload conditions and those who are undergoing treatment with deferoxamine also are at an increased risk for septicemia, secondary to the effect of iron on the virulence of the bacteria.[16]

In addition, Y enterocolitica septicemia usually is reported in patients with a hematologic disease, such as thalassemia, sickle cell disease, or hemochromatosis.[16, 49, 50, 51] Elderly patients and those who are malnourished also are at increased risk of developing septicemia.

Metastatic infections following Y enterocolitica septicemia include focal abscesses in the liver, kidneys, spleen, and lungs. Cutaneous manifestations include cellulitis, pyomyositis, pustules, and bullous lesions. Pneumonia, meningitis, panophthalmitis, endocarditis, infected mycotic aneurysm, and osteomyelitis also may occur.[48]

Testing should be done for Yersinia enterocolitica in people with persistent abdominal pain (especially school-aged children with right lower quadrant pain mimicking appendicitis who may have mesenteric adenitis), and in people with fever at epidemiologic risk for yersiniosis, including infants with direct or indirect exposures to raw or undercooked pork products.

• Stool culture - This is the best way to confirm a diagnosis of Y enterocolitica[2, 3] ; the culture result usually is positive within 2 weeks of disease onset

• If Yersinia infection is suspected, the clinical laboratory should be notified and instructed to culture on cefsulodin-irgasan-novobiocin (CIN) or other specific media for growing it at 25 degrees celsius. Y enterocolitica is non-lactose fermenting, oxidase negative, and urease positive.

• Diagnosis is made by isolating the organism from stool, blood, bile, wound, throat swab, mesenteric lymph node, cerebrospinal fluid, or peritoneal fluid.

• GI panel multiplex PCR can be used for diagnositic purposes. Yersinia is included as a target on 3 commercial, FDA-cleared, multiplex assays for the detection of gastrointestinal pathogens, ie, Verigene EP, FilmArray GI, and xTAG GPP.[4]

• Clinical consideration should be included in the interpretation of results of multiple-pathogen nucleic acid amplification tests because these assays detect DNA and not necessarily viable organisms.

• Imaging studies - Ultrasonography or computed tomography (CT) scanning may be useful in delineating true appendicitis from pseudoappendicitis.

• Colonoscopy - Findings may vary and are relatively nonspecific.

• In case of Yersinia- associated post infectious reactive arthropathy, joint aspirate would be culture negative. However, Yersinia rarely may also cause pyogenic osteoarthrits or osteomyelitis in acute invasive settings with hematogenous spread.

• Enzyme-linked immunosorbent assays and radioimmunoassays for antibodies detection. Patients who developed reactive arthritis tended to maintain Ig A and Ig G anti Yersinia antibodies.[52]

• Gram stain of Yersinia enterocolitica.

Stool samples tested for leukocytes usually produce positive results, but Y enterocolitica is difficult to distinguish from other invasive pathogens. Stool samples from infected patients should be handled carefully to avoid infecting others.

When Y enterocolitica infection is suspected, instruct the microbiology laboratory to use cefsulodin-Irgasan-novobiocin (CIN) agar, which is a differential selective medium with increased yield for Y enterocolitica. It requires 18-20 hours of incubation at 25°C to create unique colony morphology, representing 0.5- to 1-mm colonies with a red "bull's-eye" and a clear border. Use of this media allows differentiation between Y enterocolitica and Y enterocolitica– like isolates.

When using conventional enteric media, MacConkey agar incubated at 25°C for 48 hours produces the best results.[53]

Recovery of organisms from otherwise sterile samples, such as blood, cerebrospinal fluid (CSF), and lymph node tissue, usually is faster than recovery from stool samples. Isolation of Y enterocolitica from stool is hampered by slow growth and overgrowth of normal flora.

Serodiagnosis is possible with various methods, including tube agglutination, enzyme-linked immunosorbent assays, and radioimmunoassays. However, carefully interpret the serotest results for Y enterocolitica infection if a positive stool culture result is absent. Cross-reactions with other organisms can occur—including with Brucella, Morganella, and Salmonella —and a background seroprevalence rate among different populations may confound the diagnosis by acting as a false-positive result.

Agglutinin titers typically increase 1-2 weeks after infection and peak at 1:200. However, elevated levels can be found for years after infection, which also limits the usefulness of serodiagnosis.

Advanced experimental techniques for diagnosis of Y enterocolitica infection include polymerase chain reaction (PCR) assay, immunohistochemical staining, and DNA microarray. Diagnostic DNA microarray for pathogenetic organisms is a technique that is used to identify multiple genes from different kinds of pathogens, allowing it to be used to detect different species, biotypes, and/or toxins of pathogenic organisms in the same specimens. This is the major advantage over the conventional PCR assay technique, which is used to identify only 1 gene from a hybridization. DNA microarray also is more sensitive and accurate than the multiplex PCR.[54]

Typically, in patients with Y enterocolitica infection, the cecum contains aphthoid lesions and the terminal ileum has small, round elevations and ulcers (as seen in the image below). An exudate may be present. The left side of the colon typically is unaffected, but case reports have described left-sided colitis with serotype O:8.

Histologic findings in Y enterocolitica infection are consistent with acute and chronic inflammation. Yersiniosis does not produce unique histologic findings. Epithelial cell granulomas with suppuration of the centers of the granulomas (central microabscesses) have been reported. These granulomas were composed of numerous histiocytes with or without epithelioid cell features, along with scattered small T-lymphocytes and plasmacytoid monocytes.[55]

Care in patients with Y enterocolitica infection primarily is supportive, with good nutrition and hydration being mainstays of treatment.[5]

Reduced osmolarity oral rehydration solution (ORS) is recommended as the first-line therapy of mild to moderate dehydration in infants, children, and adults with acute diarrhea from any cause, and in people with mild to moderate dehydration associated with vomiting or severe diarrhea. Isotonic intravenous fluids such as lactated Ringer’s and normal saline solution should be administered when there is severe dehydration, shock, or altered mental status and failure of ORS therapy or ileus. Anti-motility drugs generally should be avoided in the setting of acute diarrhea. Antiemetic may be considered if needed.

Most infections are self-limiting. Antibiotics should be given for severe cases. Y enterocolitica isolates usually are susceptible to trimethoprim-sulfamethoxazole, aminoglycosides, third-generation cephalosporins, fluoroquinolones, and tetracyclines; they typically are resistant to first-generation cephalosporins and most penicillins. Trimethoprim-Sulfamethoxazole is the preferred antibiotic. Cefotaxime and ciprofloxacin are preferred alternatives. Antimicrobial therapy has no effect on postinfectious sequelae.[6]

In the event of an acute outbreak of Y enterocolitica, attempt to isolate persons who have been in contact with the index patient. Public health should be notified in case of foodborne disease outbreak.

Surgical therapy

Abscesses may require surgical drainage. Surgical exploration may be warranted if appendicitis cannot safely be ruled out.

Laparotomy findings in Y enterocolitica infection usually include mesenteric lymphadenitis and terminal ileitis, with a healthy appendix.

Consultations

The diagnosis and management of yersiniosis do not require specific consultations. However, consultation with an infectious diseases specialist or gastroenterologist may be useful. Consultation with a rheumatologist may be helpful in cases of erythema nodosum or reactive arthritis.

The value of antibiotic therapy in uncomplicated acute diarrhea has not been established. Diarrhea should be managed with fluid and electrolyte replacement. Avoid antimotility medications, which could lead to bacteremia.

In cases of severe enterocolitis, antibiotics have shown some benefit in terms of shortening the duration of illness. Patient populations who should be considered for empiric antibiotic therapy include the following:

• Elderly patients

• Patients with diabetes

• Patients with cirrhosis

• Immunocompromised patients

• Patients with cancer who are receiving chemotherapy

• Healthcare and childcare workers who are at an increased risk for person-to-person spread

Antibiotic treatment should be used in patients with bacteremia with extraintestinal manifestations. They should be used in cases of primary extraintestinal disorders, such as the following:

• Cellulitis

• Ophthalmitis

• Endocarditis

• Meningitis

• Osteomyelitis

• Pneumonia

• Focal abscesses

Admit patients with Y enterocolitica infection who have evidence of severe dehydration, malnourishment, or septicemia.

Patients with conditions that place them at risk for Y enterocolitica septicemia, including the following, should be monitored closely and admitted for supportive measures and antibiotic therapy at the first sign of disseminated disease:

• Elderly patients

• Patients who are immunocompromised

• Patients who are chronically ill

• Patients with iron overload

• Patients with chronic hemolysis

• Patients with alcoholism

• Patients with diabetes mellitus

• Patients on deferoxamine therapy

The following steps can be taken to prevent the spread of Y enterocolitica infection:

• Instruct patients and at-risk individuals about appropriate hygiene methods and signs and symptoms of infection

• Encourage public awareness of Y enterocolitica outbreaks and modes of transmission

• Hand washing and control of environmental cross-contamination are principal measures in reducing the spread of enteric pathogens in daycare centers, healthcare settings, and pet-care facilities, as well as within households

• In blood banks, donors should be asked about any recent symptoms of gastroenteritis

• Unwashed raw vegetables, uncooked meats (especially pork), and unpasteurized milk should be avoided[16, 17]

• Reservoirs should be eliminated

• The contamination of food products should be minimized

• Enteric precautions should be instituted in the care of patients who have been hospitalized with infection

Most infections are self-limiting. Antibiotics should be given for severe cases. Y enterocolitica isolates usually are susceptible to trimethoprim-sulfamethoxazole, aminoglycosides, third-generation cephalosporins, fluoroquinolones, and tetracyclines; they typically are resistant to first-generation cephalosporins and most penicillins as the organism often produces beta-lactamase. Trimethoprim-sulfamethoxazole is the preferred antibiotic. Cefotaxime and ciprofloxacin are preferred alternatives. Antimicrobial therapy has no effect on postinfectious sequelae.[6]

Clinical failure with cefotaxime has been reported.[56] Resistance to macrolides and fluoroquinolones is sporadically reported.[57]

Antimotility agents are contraindicated in the treatment of Y enterocolitica infection because of the increased risk for invasion.

 

Class Summary

The value of antibiotic therapy in uncomplicated acute colitis and mesenteric adenitis is not established. Antibiotic treatment may be required in patients with septicemia, with focal extraintestinal manifestations, and in immunocompromised patients with enterocolitis.

Ciprofloxacin (Cipro)

The bactericidal agent ciprofloxacin is a second-generation quinolone. It acts by interfering with DNA gyrase, by inhibiting the relaxation of supercoiled DNA, and by promoting the breakage of double-stranded DNA. Ciprofloxacin is highly active against gram-negative and gram-positive organisms.

Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra DS)

Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra DS)

The combination antibiotic TMP-SMZ inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. It is not helpful in cases of uncomplicated gastroenteritis.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with gram-negative activity.

Gentamicin

Gentamicin is an aminoglycoside that is bactericidal for susceptible gram-negative organisms. This agent is not helpful for uncomplicated gastroenteritis.

Cefotaxime (Claforan)

Cefotaxime is a third-generation cephalosporin with a gram-negative spectrum. It has lower efficacy against gram-positive organisms. This agent is not helpful for uncomplicated gastroenteritis.

Tetracycline

Tetracycline treats gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. It inhibits bacterial protein synthesis by binding with the 30S and possibly 50S ribosomal subunit(s).

Chloramphenicol

Chloramphenicol binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. It is effective against gram-negative and gram-positive bacteria.

Piperacillin and tazobactam sodium (Zosyn)

This drug combination consists of an antipseudomonal penicillin plus a beta-lactamase inhibitor. It inhibits the biosynthesis of cell wall mucopeptide and is effective during the active multiplication stage.

Imipenem/cilastatin (Primaxin)

In vitro susceptibility to imipenem has been reported.