The Enterobacteriaceae is a diverse group of aerobic Gram-negative organisms. Included in this category are E. coli, Salmonella and Shigella.
Escherichia coli infection
E. coli is commonly responsible for urinary tract infections, bacteraemia, neonatal meningitis, and peritoneal and biliary infections. Such infections are indistinguishable from similar clinical conditions caused by other bacteria. E. coli responsible for enteric disease have different serotype characteristics from those that cause disease elsewhere in the body. Four main categories of E. coli capable of producing human diarrhoeal disease are recognized.
1 Enterotoxigenic E. coli (ETEe) produces a diarrhoeal illness that is mediated through a heat-labile toxin (LT) and/or a heat-stable toxin (ST). Toxin production is genetically encoded by transferable DNA plasmids. LT resembles cholera toxin in its mode of action since it also acts via cyclic AMP and is associated with massive secretion of water and electrolytes into the intestinal lumen. ST activates guanylate cyclase with elevation of cyclic GMP levels and subsequent secretion of water and electrolytes. Clinically ETEe produces three syndromes:
(a) An illness indistinguishable from severe cholera.
(b) ‘Traveller’s diarrhoea’, a milder disease.
(c) Diarrhoea of varying severity in children, especially in developing countries.
2 Enteroinvasive E. coli (EIEe) produces an illness similar to that produced by Shigella (see below).
3 Enteropathogenic E. coli (EPEe) attaches to and damages intestinal epithelium, producing diarrhoea, primarily in children below 2 years of age. Toxins arethought to be involved in the production of diarrhoea.
Epidemics are common, especially in nurseries.
4 Enterohaemorrhagic E. coli (EHEC) produce a shigalike cytotoxin that causes bloody diarrhoea and colitis. Fever is unusual. Outbrealcs have been linked with contaminated food, particularly hamburgers.
Oral administration of fluids and electrolytes is the mainstay of therapy for E. coli gut infections as many are selflimiting and require no specific antimicrobial therapy. For severe infection, particularly with colitis and a systemic illness, ciprofloxacin 500 mg twice daily is often used as resistance to ampicillin and co-trimoxazole is widespread. Gentamicin 2-5 mg kg-l daily or tobramycin 3-5 mg kg-t daily in divided 8-hourly doses are used in severe illness with septicaemia. Urinary tract infection is discussed on. Trimethoprim and doxycycline have been used in the prophylaxis of ETEC Traveller’s diarrhoea, but early treatment rather than prophylaxis is now recommended.
Salmonella is a Gram-negative, generally motile bacillus. Biochemically three species are recognized-So typhi and S. paratyphi, S. choleraesuis and S. enteritidis. Their thermal death point is 60°C but they can withstand freezing and dry conditions for prolonged periods of time. Although salmonellae have a worldwide distribution, they usually result in disease only where there is poor hygiene and overcrowding. Transmission occurs by ingestion of contaminated foods (particularly eggs and poultry products) or water. In the past few years there has been a dramatic increase in S. enteritidis phage type 4 illnesses owing to widespread contamination of battery chickens.
The organism is found in the alimentary tract, the oviducts and within the egg itself. In the UK, spread is often by carriers, usually food handlers, who contaminate the food. Following ingestion, the salmonellae colonize the small intestine and proliferate in Peyer’s patches. They are then carried through the lymphatics, enter the bloodstream, and are thereby transported to the reticuloendothelial system. A spectrum of clinical syndromes due to Salmonella is recognized:
• Enteric fever (typhoid or paratyphoid fever)
• Extra-intestinal focal infections, e.g. osteomyelitis
• Food poisoning
This is caused by S. typhi. Humans are the only known reservoirs. The incubation period is usually 10-14 days. The onset is insidious, with headache being a prominent symptom. The fever is remittent and gradually increases in severity in a step-ladder fashion over 3-4 days. Cough, sore throat and altered behaviour may also be present. Constipation is usually present initially and diarrhoea only occurs late in the disease. Physical examination during the first week reveals a toxic individual with a relative bradycardia. During the second week several physical signs can be elicited. An erythematous maculopapular rash that blanches on pressure and is referred to as ‘rose spots’ appears, chiefly on the upper abdomen and thorax, and lasts for only 2-3 days. These spots are not easily visible on dark-skinned patients. A soft splenomegaly occurs in about 75% of patients. Cervicallymphadenopathy, hepatomegaly (present in about 30% of patients) and right iliac fossa tenderness are other physical signs that may be present. The third week of illness, aptly referred to as ‘the week of complications’, is the time when the majority of complications occur. These include lobar pneumonia, haemolyti c anaemia, meningitis, peripheral neuropathy, acute cholecystitis, urinary tract infection and osteomyelitis. Intestinal perforation occurs in 2-3% and intestinal haemorrhage in 2-8%. The fourth week of illness (‘the week of convalescence’) is characterized by a gradual return to health.
Leucopenia is present. Blood cultures are positive in about 80% during the first week and 30% in the third week. Urine cultures are helpful during the second week and stool cultures during the second to fourth week. Marrow cultures are occasionally helpful. Of the serological tests, the Widal test, which measures serum agglutinins against the 0 and H antigens, is most helpful; a fourfold increase in titre in sequential blood samples is suggestive of Salmonella infection.
Carriers can be divided into chronic carriers, defined as individuals who excrete Salmonella for at least 1 year, and convalescent carriers. The presence of Vi agglutinin in the serum in a dilution greater than 1 : 10 is suggestive of acarrier state. Since the gallbladder is frequently the focus of infection, duodenal aspirates for culture of the bilecontaining duodenal juice may yield useful information.
Chloramphenicol is effective but increasing resistance is developing. Ciprofloxacin 500 mg twice daily is therefore being used but is expensive. The temperature may take 4- 6 days before settling, although subjective improvement is noted earlier. Treatment should be continued for 2 weeks. Co-trimoxazole 960 mg daily and ampicillin 6 g daily are also effective. Complications such as intestinal perforation or haemorrhage may occur despite adequate treatment. These complications can often be managed conservatively. Eradication of a carrier state can be difficult, but ciprofloxacin for 4 weeks may be effective. Chemotherapy does not effect a cure in about 40%. In such individuals cholecystectomy remains the only mode of treatment.
Prevention and control
This includes provision of safe drinking water, sanitary disposal of excreta and proper attention to hygiene by those who handle food. The parenteral monovalenttyphoid vaccine is used as it is less likely to produce local and systemic reactions, but protection is incomplete and relatively short-lived (1 year). An improved parenteral vaccine based on the Vi polysaccharide antigen gives protection for about 3 years. An attenuated strain of S. typhi (Ty 21a) is available as a live oral vaccine and appears to confer moderately good protection for 3 years.
Paratyphoid fever is due to S. paratyphi A, B or C. They result in an illness clinically indistinguishable from typhoid fever. However, paratyphoid fever is a milder illness. Treatment is with co-trimoxazole 960 mg daily for 2 weeks.
This is an acute, short-lived infection, and is usually due to S. enteritidis serotype typhimurium. It is generally mild, lasting 2-3 days, and presents with fever, malaise, cramping abdominal pain, bloody diarrhoea and vomiting. Occasionally a cholera-like picture may be present. Treatment is symptomatic. This Salmonella is an important cause of food poisoning; other organisms responsible are shown in and are notifiable in the UK. As with typhoid fever, a chronic carrier state may develop. Treatment is as described for S. typhi carriers.