Infection lec.3 Dr. Ahmed Moyed HusseinGastrointestinal bacterial infections
Acute diarrhea, sometimes with vomiting, is the predominant symptom in infective gastroenteritis. The World Health Organization (WHO) estimates that there are more than 1000 million cases of acute diarrhea annually in developing countries, with 3–4 million deaths, half of these in infants and children. In developed countries, diarrhea remains an important problem and the elderly are most vulnerable. The majority of episodes are due to infections spread by the faecal–oral route and transmitted either on fomites, on contaminated hands, or in food or water. Measures such as the provision of clean drinking water, appropriate disposal of human and animal sewage, and the application of simple principles of food hygiene can all limit gastroenteritis.
The clinical features of food-borne gastroenteritis vary. Some organisms (Bacillus cereus, Staph. aureus and Vibrio cholerae) elute exotoxins which cause vomiting and/or so-called ‘secretory’ diarrhea (watery diarrhea without blood or faecal leucocytes, reflecting small bowel dysfunction). In general, the time from ingestion to the onset of symptoms is short and, other than dehydration, little systemic upset occurs.
Other organisms, such as Shigella spp., Campylobacter spp. and enterohaemorrhagic E. coli (EHEC), may directly invade the mucosa of the small bowel or produce cytotoxins that cause mucosal ulceration, typically affecting the terminal small bowel and colon. The incubation period is longer and more systemic upset occurs, with prolonged bloody diarrhea.
Salmonella spp. are capable of invading enterocytes, and of causing both a secretory response and invasive disease with systemic features. This is seen with Salmonella typhi and S. paratyphi (enteric fever), and, in the immunocompromised host, with non-typhoidal Salmonella spp.
The history should address foods ingested, duration and frequency of diarrhea, presence of blood or steatorrhoea, abdominal pain and tenesmus, and whether other people have been affected. Fever and bloody diarrhea suggest an invasive, colitic, dysenteric process. An incubation period of less than 18 hours suggests toxin-mediated food poisoning, and longer than 5 days suggests diarrhea caused by protozoa or helminths. Person-to-person spread suggests certain infections, such as shigellosis or cholera.
Examination includes assessment of the degree of dehydration by skin turgor, pulse and blood pressure measurement. The urine output and ongoing stool losses should be monitored.
stool examination for blood and microscopy for leucocytes, and also an examination for ova, cysts and parasites if the history indicates former tropical residence or travel.
Stool culture should be performed.
FBC and serum electrolytes indicate the degree of inflammation and dehydration.
All patients with acute, potentially infective diarrhea should be appropriately isolated to minimize person to- person spread of infection.
Fluid replacement:Replacement of fluid losses in diarrheal illness is crucial and may be life-saving. The fluid lost in diarrhea is isotonic, so both water and electrolytes need to be replaced.
Oral rehydration solutions (ORS) contain sugars, water and electrolytes and can be just as effective as intravenous replacement fluid.
The volume of fluid replacement required should be estimated based on the following considerations.
• Replacement of established deficit: After 48 hours of moderate diarrhea (6–10 stools per 24 hours), the average adult will be 2–4 L depleted from diarrhea alone. Associated vomiting will compound this. Adults with this symptomatology should therefore be given rapid replacement of 1–1.5 L, either orally (ORS) or by intravenous infusion (normal saline), within the first 2–4 hours of presentation.
• Replacement of ongoing losses: The average adult’s diarrheal stool accounts for a loss of 200 mL of isotonic fluid. Stool losses should be carefully charted and an estimate of ongoing replacement fluid calculated.
• Replacement of normal daily requirement: The average adult has a daily requirement of 1–1.5 L of fluid in addition to the calculations above. This will be increased substantially in fever or a hot environment.
Antimicrobial agents:In non-specific gastroenteritis, antibiotics have been shown to shorten symptoms by only 1 day in an illness usually lasting 1–3 days. This benefit, when related to the potential for the development of antimicrobial resistance or side-effects, does not justify treatment, except if there is systemic involvement, a host with immunocompromise or significant comorbidity.
Conversely, antibiotics are indicated in Sh. Dysenteriae infection and in invasive salmonellosis – in particular, typhoid fever. Antibiotics may also be advantageous in cholera epidemics, reducing infectivity and controlling the spread of infection.
Antidiarrhoeal, antimotility and antisecretory agents:These agents are not usually recommended in acute infective diarrhea. Loperamide, diphenoxylate and opiates are potentially dangerous in dysentery in childhood, causing intussusception. Antisecretory agents, such as bismuth and chlorpromazine, may be effective but can cause significant sedation. They do not reduce stool fluid losses, although the stools may appear more bulky. Adsorbents, such as kaolin or charcoal, have little effect.
Staphylococcal food poisoningStaph. aureus transmission takes place via the hands of food handlers to foodstuffs such as dairy products, including cheese, and cooked meats. Inappropriate storage of these foods allows growth of the organism and production of one or more heat-stable enterotoxins which cause the symptoms.
Nausea and profuse vomiting develop within 1–6 hours. Diarrhoea may not be marked. The toxins that cause the syndrome act as ‘superantigens’, inducing a significant neutrophil leucocytosis that may be clinically misleading. Most cases settle rapidly but severe dehydration can occasionally be life-threatening.
Antiemetics and appropriate fluid replacement are the mainstays of treatment. Suspect food should be cultured for staphylococci and demonstration of toxin production.
Bacillus cereus food poisoningIngestion of the pre-formed heat-stable exotoxins of B. cereus causes rapid onset of vomiting and some diarrhea within hours of food consumption, which resolves within 24 hours. Fried rice and freshly made sauces are frequent sources; the organism grows and produces enterotoxin during storage. The disease is self-limiting but can be quite severe. Rapid and judicious fluid replacement and appropriate notification of the public health authorities are all that is required.
CholeraCholera, caused by Vibrio cholerae serotype O1, is the archetypal toxin-mediated bacterial cause of acute watery diarrhea. The enterotoxin activates adenylate cyclase in the intestinal epithelium, inducing net secretion of chloride and water. V. cholerae O1 has two biotypes: classical and El Tor, and each of these has two distinct serotypes, Inaba and Ogawa.
Infection spreads via the stools or vomit of symptomatic patients or of the much larger number of subclinical cases. Organisms survive for up to 2 weeks in fresh water and 8 weeks in salt water. Transmission is normally through infected drinking water, shellfish and food contaminated by flies, or on the hands of carriers.
Clinical features:Severe diarrhea without pain or colic begins suddenly and is followed by vomiting. Following the evacuation of normal gut faecal contents, typical ‘rice water’ material is passed, consisting of clear fluid with flecks of mucus.
Classical cholera produces enormous loss of fluid and electrolytes, leading to intense dehydration with muscular cramps. Shock and oliguria develop but mental clarity remains. Death from acute circulatory failure may occur rapidly unless fluid and electrolytes are replaced. Improvement is rapid with proper treatment.
The majority of infections, however, cause mild illness with slight diarrhea. Occasionally, a very intense illness, ‘cholera sicca’, occurs, with loss of fluid into dilated bowel, killing the patient before typical gastrointestinal symptoms appear. The disease is more dangerous in children.
Diagnosis and management:
Clinical diagnosis is easy during an epidemic. Otherwise, the diagnosis should be confirmed bacteriologically. Stool dark-field microscopy shows the typical ‘shooting star’ motility of V. cholerae. Rectal swab or stool cultures allow identification. Cholera is notifiable
under international health regulations.
Maintenance of circulation by replacement of water and electrolytes is paramount. Ringer-Lactate is the best fluid for intravenous replacement. Vomiting usually stops once the patient is rehydrated, and fluid should then be given orally up to 500 mL hourly. Early intervention with oral rehydration solutions that include resistant starch, based on either rice or cereal, shortens the duration of diarrhea and improves prognosis. Total fluid requirements may exceed 50 L over a period of 2–5 days. Accurate records are greatly facilitated by the use of a ‘cholera cot’, which has a reinforced hole under the patient’s buttocks, beneath which a graded bucket is placed.
Three days treatment with tetracycline 250 mg 4 times daily, a single dose of doxycycline 300 mg or ciprofloxacin 1 g in adults reduces the duration of excretion of V. cholerae and the total volume of fluid needed for replacement.
Strict personal hygiene is vital and drinking water should come from a clean piped supply or be boiled. Flies must be denied access to food. Parenteral vaccination with a killed suspension of V. cholerae provides some protection. Oral vaccines containing killed V. cholera and the B subunit of cholera toxin are available but are of limited efficacy.
In epidemics, public education and control of water sources and population movement are vital. Mass single-dose vaccination and treatment with tetracycline are valuable. Disinfection of discharges and soiled clothing, and scrupulous hand-washing by medical attendants reduce the danger of spread.
Vibrio parahaemolyticus infectionThis marine organism produces a disease similar to enterotoxigenic E. coli. It is acquired from raw seafood and is very common where ingestion of such food is widespread (e.g. Japan). After an incubation period of approximately 20 hours, explosive diarrhea, abdominal cramps and vomiting occur. Systemic symptoms of headache and fever are frequent but the illness is self-limiting after 4–7 days. Rarely, a severe septicaemic illness arises; in this case, V. parahaemolyticus can be isolated using specific halophilic culture.
Campylobacter jejuni infectionThis infection is essentially a zoonosis, although contaminated water may be implicated, as the organism can survive for many weeks in fresh water. The most common sources of the infection are chicken, beef and contaminated milk products. Campylobacter infection is now the most common cause of bacterial gastroenteritis in the UK, accounting for some 100 000 cases per annum, most of which are sporadic.
The incubation period is 2–5 days. Colicky abdominal pain, which may be quite severe and mimic surgical pathology, occurs with nausea, vomiting and significant diarrhea, frequently containing blood. The majority of Campylobacter infections affect fit young adults and are self-limiting after 5–7 days. About 10–20% will have prolonged symptomatology, occasionally meriting treatment with antibiotics such as erythromycin, as many organisms are resistant to ciprofloxacin.
Approximately 1% of cases will develop bacteraemia and possible distant foci of infection. Campylobacter spp. have been linked to Guillain–Barré syndrome and postinfectious reactive arthritis.
Salmonella spp. InfectionSalmonella serotypes other than S. typhi and S. paratyphi, of which there are more than 2000, are subdivided into five distinct subgroups which produce gastroenteritis.
They are widely distributed throughout the animal kingdom. Two serotypes are most important worldwide: S. enteritidis and S. typhimurium. Transmission is by contaminated water or food, particularly poultry, egg products and related fast foods, direct person-to-person spread or the handling of exotic pets such as salamanders, lizards or turtles.
The incubation period of Salmonella gastroenteritis is 12–72 hours and the predominant feature is diarrhea, sometimes with passage of blood. Vomiting may be present at the outset. Approximately 5% of cases are bacteraemic. Reactive (post-infective) arthritis occurs in approximately 2%.
Antibiotics are not indicated for uncomplicated Salmonella gastroenteritis. However, evidence of bacteraemia is a clear indication for antibiotic therapy.
Yersinia enterocolitica infectionThis organism, commonly found in pork, causes mild to moderate gastroenteritis and can produce significant mesenteric adenitis after an incubation period of 3–7 days. It predominantly causes disease in children but adults may also be affected. The illness resolves slowly, with 10–30% of cases complicated by persistent arthritis or Reiter’s syndrome.
Escherichia coli infectionMany serotypes of E. coli are present in the human gut at any given time. Production of disease depends on either colonization with a new or previously unrecognized strain, or the acquisition by current colonizing
bacteria of a particular pathogenicity factor for mucosal attachment or toxin production. Travel to unfamiliar areas of the world allows contact with different strains of endemic E. coli and the development of travellers’ diarrhea.
At least five different clinico-pathological patterns of diarrhea are associated with specific strains of E. coli with characteristic virulence factors.
Enterotoxigenic E. coli:Enterotoxigenic E. coli (ETEC) cause the majority of cases of travellers’ diarrhea in developing countries. The organisms produce either a heat-labile or a heat-stable enterotoxin, causing marked secretory diarrhea and vomiting after 1–2 days’ incubation. The illness is usually mild and self-limiting after 3–4 days. Antibiotics, such as ciprofloxacin, have been used to limit the duration of symptoms.
Entero-invasive E. coli:Illness caused by entero-invasive E. coli (EIEC) is very similar to Shigella dysentery and is caused by invasion and destruction of colonic mucosal cells. No enterotoxin is produced. Acute watery diarrhea, abdominal cramps and some scanty blood-staining of the stool are common. The symptoms are rarely severe and are usually self-limiting.
Enteropathogenic E. coli and Entero-aggregative E. coli:Enteropathogenic E. coli (EPEC) and Entero-aggregative E. coli (EAEC) organisms are very important in infant and children diarrhea. They are able to attach to the gut mucosa, inducing a specific ‘attachment and effacement’ lesion, and causing destruction of microvilli and disruption of normal absorptive capacity. The symptoms vary from mild non-bloody diarrhea to quite severe illness, but without bacteraemia.
Enterohaemorrhagic E. coli:The reservoir of infection is in the gut of herbivores. The organism has an extremely low infecting dose (10– 100 organisms). Runoff water from pasture lands where cattle have grazed, which is used to irrigate vegetable crops, as well as contaminated milk, meat products (especially hamburgers which have been incompletely cooked), lettuce, radish shoots and apple juice, have all been implicated as sources.
The incubation period is between 1 and 7 days. Initial watery diarrhea becomes frankly and uniformly bloodstained in 70% of cases and is associated with severe and often constant abdominal pain. There is little systemic upset, vomiting or fever.
Enterotoxins have both a local effect on the bowel and a distant effect on particular body tissues, such as glomerular apparatus, heart and brain. The potentially life-threatening haemolytic uraemic syndrome (HUS) occurs in 10–15% of sufferers from this infection, arising 5–7 days after the onset of symptoms. It is most likely at the extremes of age, is heralded by a high peripheral leucocyte count, and may be induced, particularly in children, by antibiotic therapy.
Bacillary dysentery (shigellosis)Shigellae are Gram-negative rods, closely related to E. coli, that invade the colonic mucosa. There are four main groups: Sh. dysenteriae, flexneri, boydii and sonnei. In the tropics, bacillary dysentery is usually caused by Sh. flexneri, whilst in the UK most cases are caused by Sh. sonnei. Shigellae are often resistant to multiple antibiotics, especially in tropical countries. The organism only infects humans and its spread is facilitated by its low infecting dose of around 10 organisms.
Spread may occur via contaminated food or flies, but transmission by unwashed hands after defecation is by far the most important factor. Outbreaks occur in mental hospitals, residential schools and other closed institutions.
Disease severity varies from mild Sh. sonnei infections that may escape detection to more severe Sh. Flexneri infections, while those due to Sh. dysenteriae may be fulminating and cause death within 48 hours.
In a moderately severe illness, the patient complains of diarrhea, colicky abdominal pain and tenesmus. Stools are small, and after a few evacuations contain blood and purulent exudate with little faecal material.
Fever, dehydration and weakness occur, with tenderness over the colon. Arthritis or iritis may occasionally complicate bacillary dysentery (Reiter’s syndrome), associated with HLA-B27.
Management and prevention:
Oral rehydration therapy or, if diarrhea is severe, intravenous replacement of water and electrolyte loss is necessary. Antibiotic therapy with ciprofloxacin (500 mg twice daily for 3 days) is effective in known shigellosis and appropriate in epidemics. The use of antidiarrhoeal medication should be avoided.
The prevention of faecal contamination of food and milk and the isolation of cases may be difficult, except in limited outbreaks. Hand-washing is very important.
Clostridium difficile infectionC. difficile is the most commonly diagnosed cause of antibiotic-associated diarrhea, and is an occasional constituent of the normal intestinal flora. C. difficile is capable of producing two toxins (A and B). C. difficile infection (CDI) usually follows antimicrobial therapy, which alters the composition of the gastrointestinal flora and may result in colonization with C. difficile if the patient is exposed to C. difficile spores. The combination of toxin production and the ability to produce
environmentally stable spores accounts for the clinical features and transmissibility of CDI.
Disease manifestations range from diarrhea to life-threatening pseudomembranous colitis. Around 80% of cases occur in people over 65 years of age, many of whom are frail with comorbid diseases. Symptoms
usually begin in the first week of antibiotic therapy but can occur at any time up to 6 weeks after treatment has finished. The onset is often insidious, with lower abdominal pain and diarrhea which may become profuse and watery. The presentation may resemble acute ulcerative colitis with bloody diarrhea, fever and even toxic dilatation and perforation. Ileus is also seen in pseudomembranous colitis.
C. difficile can be isolated from stool culture in 30% of patients with antibiotic-associated diarrhea and over 90% of those with pseudomembranous colitis, but also from 5% of healthy adults and up to 20% of elderly patients in residential care. The diagnosis of CDI therefore rests on detection of toxins A or B in the stool.
Current practice in the UK is to screen stool from patients with a compatible clinical syndrome by detection either of glutamate dehydrogenase (GDH), an enzyme produced by C. difficile, or of C. difficile nucleic acid (e.g. by PCR); if screening is positive, a C. difficile toxin ELISA or a tissue culture cytotoxicity assay is performed.
The rectal appearances at sigmoidoscopy may be characteristic, with erythema, white plaques or an adherent pseudomembrane. Appearances may also resemble those of ulcerative colitis. In some cases, the rectum is spared and abnormalities are observed in the proximal colon.
The precipitating antibiotic should be stopped and the patient should be isolated. Supportive therapy with intravenous fluids and resting of the bowel is often needed. CDI is treated with antibiotics. The options for first-line therapy are metronidazole (500 mg orally 3 times daily for 10 days) or vancomycin (125 mg orally 4 times daily for 7–10 days).
A new agent, fidaxomicin, is associated with a lower relapse rate than vancomycin. Intravenous immunoglobulin and/or corticosteroids are sometimes given in the most severe or refractory cases and faecal transplantation is also emerging as a therapy in relapsing patients. Surgical intervention is sometimes needed and needs to be considered early in severe cases.