The ultrasound shows a liver abscess in the right lobe and, in view of his travel, an amoebic abscess is a strong possibility. Fortunately, you had sent off an amoebic CFT sample and you ring the reference laboratory urgently. The test is positive (usually positive with an amoebic liver abscess).

Treatment

Treat with metronidazole 800 mg × 3 daily for 10 days followed by diloxanide furoate 500 mg × 3 daily for 10 days. Aspiration of the abscess is only required with failure of medical therapy.

Remember

• Take a careful history: always repeat

• Examine the patient thoroughly: always repeat

• Initial investigations often give a clue to the diagnosis: often need repeating

• Be patient and don’t give antibiotics until diagnosis is made unless the patient is very sick

• Perform invasive and/or expensive investigations only when appropriate, e.g. echo, CT scan/MRI, bone marrow and culture, lymph node/liver biopsy.

Progress.

This man responded quickly to therapy with loss of pain, improvement in appetite and he became apyrexial after 4 days. A repeat ultrasound 3 weeks later still showed a small residual cavity.

Further reading

WHO. Infectious diseases. http://www.who.int/topics/infectiousdiseases/en

Septicaemia

Septicaemia and bacteraemia should be differentiated. In bacteraemia there is a transient presence of live organisms in the blood which do not cause symptoms; it can occur in healthy patients.

In septicaemia there are signs and symptoms of a systemic inflammatory response syndrome (SIRS) to a localized primary site of infection. SIRS is defined as the presence of two or more of: heart rate > 90/min; WCC > 12 × 10⁹/L or < 4 × 10⁹/L; a temperature > 38°C or < 36°C and a respiratory rate > 20 min or a PaCO₂ < 4.3 κPa (<32 mmHg).

Case history

A 70-year-old woman was admitted to hospital with fever, confusion and hypotension. She lived on her own and was unable to give a history.

On examination, she was clinically dehydrated, confused and had cold clammy peripheries. Pulse rate 108/min, respiratory rate 22 min.

She was also hypotensive with a BP 90/50 and had a temperature of 39°C.

Diagnosis: Septic shock.

What are the most common causes of septicaemia in patients presenting from the community?

The most common organisms isolated are Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae and pyogenic streptococci – especially group A streptococci. Neisseria meningitidis should not be forgotten as a possible cause of community-acquired sepsis.

In hospital, coagulase-negative staphylococci can also cause sepsis in immunosuppressed patients with IV lines in situ. Wounds, the respiratory tract (especially in ventilated patients) and the urinary tract (in catheterised patients) are other sources of sepsis in hospitalised patients.

What factors predispose to septicaemia?

In both Gram-positive and Gram-negative septicaemia, impaired host defences, surgery or instrumentation (including intravenous cannulae, urinary catheters and mechanical ventilation) predispose to septicaemia (Table 1.2).

Table 1.2 Predisposing factors for septicaemia

What is the differential diagnosis of septic shock?

Non-infective disorders, such as acute myocardial infarction, pulmonary embolism or drug reactions, must be excluded. Toxic shock (e.g. toxic shock syndrome) can also present in a similar manner.

What would be your initial management of this woman and what investigations would you do?

This patient required supportive therapy (e.g. fluid replacement) because she was dehydrated and oxygen was given and inotropes. Broad-spectrum antibiotics were started after blood and urine cultures had been taken. The antibiotic therapy varies according to local hospital policy and the likely focus of infection. This severely shocked patient was transferred to HDU/ITU (see p. 383).

If a urinary tract infection is thought to be the likely source, a broad-spectrum cephalosporin is often appropriate (e.g. cefuroxime) or a quinolone (e.g. ciprofloxacin).

If there is no obvious focus of infection, blind therapy must be broad spectrum and cover streptococci, staphylococci and coliforms.

Suitable choices are:

• A broad-spectrum cephalosporin such as IV cefuroxime or IV cefotaxime or IV ceftriaxone.

• Metronidazole should be added if an anaerobic infection is considered likely.

• A broad-spectrum penicillin with β-lactamase inhibitor (e.g. piperacillin/tazobactam). Gentamicin can be added if the patient is very ill.

• A carbapenem (e.g. imipenem, although this is a restricted antibiotic in many hospitals).

Remember

• If you give gentamicin, remember that you need to monitor serum levels. Combining it with a cephalosporin can potentiate its nephrotoxicity.

• Cefuroxime, ceftriaxone and cefotaxime have fairly good activity against staphylococci and streptococci, as well as against many Gram-negative rods; they have poor activity against Pseudomonas spp. Ceftazidime has poor activity against streptococci and staphylococci but excellent activity against Pseudomonas spp. and other Gram-negative organisms. No cephalosporins are active against Enterococcus spp.

• Cephalosporins are associated with C. difficile diarrhoea and should be avoided if possible.

• If a patient develops sepsis while in hospital it is possible that this is due to resistant organisms, e.g. methicillin-resistant S. aureus (MRSA) or resistant Gram-negative rods.

• If MRSA infection is considered likely and the patient is very sick, add IV vancomycin 1 g × 2 per day (assuming normal renal function) given over at least 100 minutes while awaiting culture results.

A urine sample was obtained from this patient. Microscopy found it to contain 1000 WCC/mm³ and ++ bacteria.

Progress.

The patient had already been given IV cefuroxime and was continued on this. On admission she was also given a single dose of gentamicin. The following day both her urine and blood cultures grew an E. coli that was susceptible to cefuroxime and gentamicin but resistant to amoxicillin. She made a good recovery.

Remember

Many hospitals have specific guidelines for antibiotic usage: always check or get microbiological advice.

In your hospital, do you know the approximate percentage of organisms causing urinary tract infections that are susceptible to commonly used antibiotics?

In many areas, approximately 50% of E. coli causing urinary tract infection are resistant to amoxicillin and 20–30% are resistant to trimethoprim. More than 90% are susceptible to cefuroxime, ciprofloxacin and gentamicin. You need to know local resistance patterns.

Meningococcal meningitis and septicaemia

Case history

An 18-year-old woman is brought into A&E ‘collapsed’. The previous day she had apparently been well apart from symptoms of a minor upper respiratory tract infection. She woke up feeling very unwell and asked her flat-mate to call the emergency doctor. The flat-mate noted that her friend had a couple of spots on her chest but by the time the doctor arrived she was developing a more widespread petechial rash. The emergency doctor transferred her immediately to hospital after giving her a single dose of benzylpenicillin.

The patient was febrile with a temperature of 38°C.

A petechial rash was present (Fig. 1.1).

Figure 1.1 Meningococcal rash (from Fuller, Neurology Illustrated Colour Text, with permission).

The patient was hypotensive and shocked.

There was minimal neck stiffness.

What do you think is the most likely diagnosis?

This young woman has fulminant meningococcaemia, which has a worse prognosis than meningococcal meningitis and usually has an extremely rapid downhill course.

What should the immediate management be?

Take blood and throat cultures and then start antibiotics immediately. Give intravenous benzylpenicillin, initially 2.4 g 4-hourly or IV cefotaxine 2 g × 6-hourly or IV ceftriaxone 2 g × 2 daily for presumed meningococcal meningitis/septicaemia.

Remember

The first doctor to see a patient suspected of having meningococcal septicaemia or meningitis should immediately give benzylpenicillin IM injection before immediate transfer to hospital.

Who should be informed and what further action should be taken?

The consultant (or his/her deputy) in charge of communicable disease control (CCDC) should be informed immediately by telephone if a clinical diagnosis of meningococcal disease is made. Formal notification should then be done in writing. Notification books should be kept on all wards. Rifampicin prophylaxis can then be arranged for any close contacts.

Contacts who should receive prophylaxis

• People who live in the same household as the case or who have lived there in the previous week

• Sexual partners

• Work fellows sharing a small office, i.e. an office for two

• Staff carrying out mouth-to-mouth resuscitation on the patient or ‘specialing’ the patient, especially in the first 24 h

• The patient herself at the end of her parenteral therapy

• School contacts if more than one case in a school.

Once the CCDC has been informed, he/she will usually arrange for chemoprophylaxis (Table 1.3), but might ask the hospital doctor to do this for the patient’s relatives.

Table 1.3 Recommended chemoprophylaxis of meningococcal meningitis

	First choice
	Rifampicin
Adults and children over 12 years	600 mg × 2 daily for 2 days
Children 1–12 years	10 mg/kg × 2 daily for 2 days (maximum dose 600 mg × 2 daily for 2 days)
Infants, 12 months	5 mg/kg × 2 daily for 2 days
	Other options
	Ciprofloxacin
Adults	500 mg single dose
Children	Not recommended
Pregnancy/breastfeeding mothers	Not recommended
	Ceftriaxone
Adults	250 mg IM as a single dose
Children, 12 years	125 mg IM as a single dose

Remember

The patient should have rifampicin 600 mg × 2 daily for 2 days after she has finished her parenteral antibiotics to eradicate carriage of N. meningitidis from her nasopharynx.

What should you tell people who are taking rifampicin prophylaxis?

• That it might interfere with the effectiveness of the oral contraceptive if they are taking this. Hence they should take additional contraceptive measures for the remainder of the cycle.

• That their secretions (e.g. tears) might turn orangey-pink and that their soft contact lenses will also be permanently stained unless they remove them!

Overall management

This patient was treated with intravenous ceftriaxone 2 g IV twice per day in the intensive care unit. After a stormy course she made a full recovery. There were no secondary cases.

Further reading

Quagliarello V. Dissemination of Neisseria meningitidis. New England Journal of Medicine. 2011;364:1573–1575.

Pseudomembranous colitis

This is the condition caused by Clostridium difficile; a pseudomembrane is seen on sigmoidoscopy.

Case history

A 40-year-old man who had been on the intensive care unit for 3 weeks with a head injury following a road traffic accident developed severe diarrhoea. He was on a ventilator and currently was finishing a course of a third-generation parenteral cephalosporin for hospital acquired pneumonia. According to the nurses, one other patient on the ITU currently also has diarrhoea.

What other questions do you want to ask?

You would want to know:

• What the diarrhoea is like: are the stools liquid or bloody?

• How long has the patient been on broad-spectrum antibiotics?

• Has any other patient/member of the staff got diarrhoea? (One of the ITU nurses informs you that another patient did have loose stools and you need to ascertain if this is really the case and if there were any obvious reasons for this.)

What is your differential diagnosis?

This would include:

• Antibiotic-associated diarrhoea, particularly pseudomembranous colitis

• Diarrhoea due to enteral feeding

• Other bacterial causes, e.g. Salmonella spp., Shigella spp., Campylobacter spp., E. coli 0157; these are less likely because patient hasn’t been eating but could occur as a result of cross-infection

• Viral gastroenteritis.

What investigations would you perform?

You would need to send a stool from the patient to the microbiology laboratory (and also from any other patient/staff member with diarrhoea) for microscopy, culture and sensitivity. If several patients/members of staff are affected, stools should also be sent to the virology department to look for a viral aetiology, e.g. small round viruses. In addition, you would specifically need to request an examination for Clostridium difficile (toxin) – the organism responsible for the toxin of pseudomembranous colitis. Do a sigmoidoscopy to look for the typical pseudomembrane seen in pseudomembranous colitis and to exclude inflammatory bowel disease by rectal biopsy.

The patient was thought, on clinical grounds, to have pseudomembranous colitis. This was later confirmed by the microbiology department, which found the stool to be positive for C. difficile toxin.

Remember

Culture of C. difficile itself in a stool is insufficient evidence that a patient has pseudomembranous colitis; only toxin-producing strains cause this.

How would you manage the patient?

The patient should be isolated in a side room if possible to prevent cross-infection. You need to ensure that the patient is adequately hydrated. In patients with antibiotic-associated diarrhoea, if it is at all possible, any broad-spectrum antibiotics that the patient is taking should be stopped. If it is not possible to stop all antibiotics, try and change to a narrow-spectrum agent (discuss with microbiology). Specific first-line therapy for pseudomembranous colitis is oral metronidazole 400 mg × 3 for 7–10 days. Oral vancomycin 125–250 mg × 4 for 7–10 days is used if no response to metronidazole. Fidaxomicin 200 mg is also effective.

Note: you do not need to do vancomycin levels in patients receiving oral vancomycin because it is not systemically absorbed.

Normally, metronidazole is tried first because there is a worry that use of oral vancomycin might predispose to the development of vancomycin-resistant enterococci in the gastrointestinal tract; in some parts of the world, enterococcal vancomycin resistance is becoming a major problem.

Further reading

Kupers ES, Surawicz CM. Clostridium difficile infection. Lancet. 2008;371:1486–1488.

Food poisoning: E. coli 0157

Enterohaemorrhagic Escherichia coli (EHEC)

EHEC (usually serotype O157:H7, and also known as verotoxin-producing E. coli, or VTEC) is a well recognised cause of gastroenteritis in man. It is a zoonosis usually associated with cattle, with the organism being found in the intestines of herbivores. There have been a number of major outbreaks (notably in Scotland and Japan) associated with contaminated food. Run off water from where cattle have been grazing is used in irrigation and therefore salads and vegetables are a source of infection, as well as milk and underdone beef, e.g. hamburgers.

EHEC secretes a toxin (Shiga-like toxin 1) which affects vascular endothelial cells in the gut and in the kidney. After an incubation period of 12–48 hours it causes diarrhoea (frequently bloody), associated with abdominal pain and nausea. Some days after the onset of symptoms the patient may develop thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome (HUS). This is more common in children, and may lead to permanent renal damage or death. Treatment is mainly supportive: there is evidence that antibiotic therapy might precipitate HUS by causing increased toxin release.

Case history

A 15-year-old girl is admitted to hospital with bloody diarrhoea; her parents and her three siblings are well. They have apparently all eaten the same food during the last week except on a single occasion when the patient ate a beef-burger cooked at a local party. The mother remembers that it looked rather raw inside. The girl had eaten chicken at least three times during the previous week. She looked slightly dehydrated and had a temperature of 37.8°C. Her abdomen was soft but generally tender, bowel sounds were increased.

What would your initial management be?

The patient should be admitted to MAU and put into excretion–secretion isolation (assuming a probable infective aetiology). Ensure adequate hydration. Oral/IV antibiotics can have a place in treating severe infections due to Salmonella spp., Campylobacter spp. and Shigella spp.; they should not be used in infections caused by E. coli 0157. The disease should be notified to the CCDC both by telephone immediately and in writing when the diagnosis has been made. Rapid notification is required if the patient works in the food industry or with the very young, the elderly or the immunosuppressed.

Typhoid

This is the typical form of enteric fever and is caused by Salmonella typhi. Enteric fever is an acute systemic illness with fever, headache and abdominal discomfort.

Case history

A 35-year-old Asian male presents with a 1-week history of fever, headache, a dry cough and constipation. He is resident in the UK and has just returned from a 6-week holiday in Bangladesh, where he was visiting relatives. He works as a chef in a local restaurant. While he was away, one of the relatives he was staying with had a high fever and severe diarrhoea.

On examination, the patient had a fever of 39.5°C with a pulse rate of only 85/minute. Examination of the cardiovascular, respiratory and central nervous systems was unremarkable.

The abdomen was slightly tender.

Investigations

• FBC, routine chemistry, CXR and blood cultures taken

• FBC shows a slight leucopenia

• Gram-negative rods are seen in a film of the blood cultures taken after 24-h incubation

What is the most likely diagnosis?

S. typhi (this was later confirmed as being the definitive diagnosis).

How would you manage this patient?

The patient should be nursed in a side room with excretion–secretion precautions used (consult your local infection control manual). The control of infection officer should be alerted, as should your local CCDC, as soon as a definite diagnosis is made. Your CCDC should be alerted immediately by telephone and also via the formal notification book, which should be available on every ward. This is particularly necessary because this patient is a food handler. If the patient subsequently develops diarrhoea, adequate fluids are required to avoid dehydration. Pending antibiotic sensitivity testing, the patient should be commenced on ciprofloxacin 500–750 mg × 2 daily for 10 days.

NB. Cefuroxime, although frequently used for treating Gram-negative sepsis, is not effective against S. typhi, which is an intracellular pathogen.

Remember

Ciprofloxacin is extremely well absorbed and so can be given by the oral route 500 mg 12-hourly as long as the patient is not vomiting. After starting ciprofloxacin the patient started to feel better very quickly but it took 3–6 days for the temperature to settle.

Progress.

The patient was discharged after 6 days, feeling well and with no fever. He needed a follow-up appointment to ensure that he does not become a carrier of S. typhi. He must remain away from his job as a food handler until he is known to have negative stool cultures for S. typhi.

The returning traveller

Case history

A 20-year-old student returns from a 6-week backpacking tour of Africa. Two weeks after his return he goes to A&E complaining of fever, headache and malaise of 7 days’ duration.

On examination, the patient is thin and febrile with a temperature of 38°C. There are no other abnormal findings.

What further questions do you want to ask this man?

It is essential – as always – to take a full detailed history. Particular note should be taken about exactly where the patient has travelled, what vaccinations he had prior to his trip, whether he took anti-malarial prophylaxis regularly and, if so, what he took. Did he remember being bitten by any insects? Did he have close contact with anyone who was obviously unwell? What sort of food did he eat? Did he have unprotected sex with any strangers while travelling?

Differential diagnosis is shown in Table 1.4.

Table 1.4 Causes of febrile illness in travellers returning from the tropics and world-wide

Developing countries	Specific geographical areas (see text)
Malaria	Histoplasmosis
Schistosomiasis	Brucellosis
Dengue	World-wide
Tick typhus	Influenza
Typhoid	Pneumonia
Tuberculosis	URTI
Dysentery	UTI
Hepatitis A	Traveller’s diarrhoea
Amoebiasis	Viral infection Sexually transmitted diseases

WHO advises that fever occurring in a traveller 1 week or more after entering a malaria risk area and up to 3 months after departure is a medical emergency.

URTI, upper respiratory tract infection; UTI, urinary tract infection.

Remember

Just because someone has been travelling, it does not mean that they can’t have a common type of infection such as influenza, a common cold or a sexually transmitted infection. Holidays are notorious for people picking up STIs.