Presenting problems in infectious diseases • 227

infection. Infection may be limited to tissue that is already damaged

11.9 Severe necrotising soft tissue infections (anaerobic cellulitis) or may involve healthy muscle (gas gangrene).
In anaerobic cellulitis, usually due to C. perfringens or other
• Necrotising fasciitis (primarily confined to subcutaneous fascia
clostridia infecting devitalised tissue following a wound, gas forms
and fat)
• Clostridial anaerobic cellulitis (confined to skin and subcutaneous locally and extends along tissue planes but bacteraemia does
tissue) not occur. Prompt surgical débridement of devitalised tissue
• Non-clostridial anaerobic cellulitis and therapy with penicillin or clindamycin is usually effective.
• Progressive bacterial synergistic gangrene (Staphylococcus aureus Gas gangrene (clostridial myonecrosis) is defined as acute
+ micro-aerophilic streptococcus) (‘Meleney’s gangrene’, primarily invasion of healthy living muscle undamaged by previous trauma,
confined to skin) and is most commonly caused by C. perfringens. In at least
• Pyomyositis (discrete abscesses within individual muscle groups) 70% of cases, it follows deep penetrating injury sufficient to
• Clostridial myonecrosis (gas gangrene) create an anaerobic (ischaemic) environment and allow clostridial
• Anaerobic streptococcal myonecrosis (non-clostridial infection introduction and proliferation. Severe pain at the site of the
mimicking gas gangrene)
injury progresses rapidly over 18–24 hours. Skin colour changes
• Group A streptococcal necrotising myositis
from pallor to bronze/purple discoloration and the skin is tense,
swollen, oedematous and exquisitely tender. Gas in tissues may
be obvious, with crepitus on clinical examination, or visible on
X-ray, CT or ultrasound. Signs of systemic toxicity develop
rapidly, with high leucocytosis, multi-organ dysfunction, raised
creatine kinase and evidence of disseminated intravascular
coagulation and haemolysis. Antibiotic therapy with high-dose
11
intravenous penicillin and clindamycin is recommended, coupled
with aggressive surgical débridement of the affected tissues.
Alternative agents include cephalosporins and metronidazole.
Hyperbaric oxygen has a putative but controversial role.

Other SSTIs
‘Synergistic gangrene’ is a polymicrobial infection with anaerobes
and other bacteria (Staph. aureus or Gram-negatives). When
this affects the genital/perineal area, it is known as ‘Fournier’s
gangrene’. Severe gangrenous cellulitis in immunocompromised
hosts may involve Gram-negative bacteria or fungi. Entamoeba
Fig. 11.4 Excision following necrotising fasciitis in an injection histolytica can cause soft tissue necrosis following abdominal
drug-user.
surgery in areas of the world where infection is common. Contact
with sea water or shellfish consumption in tropical to subtropical
involves organisms such as Aeromonas hydrophila and Vibrio regions worldwide, such as the Gulf of Mexico, can lead to
vulnificus, which is found in tropical to subtropical regions and infection with Vibrio vulnificus. This infection causes soft tissue
is associated with marine exposure. Type 4 is caused by fungi necrosis and bullae, and may lead to necrotising fasciitis. Patients
such as mucoraceous moulds and may also vary geographically with chronic liver disease are particularly susceptible to this
in incidence with recent reports of increased cases in India and infection and can develop sepsis.
other regions.
Necrotising fasciitis is a medical emergency, requiring immediate
surgical débridement with inspection of the involved muscle Acute diarrhoea and vomiting
groups, in addition to antimicrobial therapy (Fig. 11.4). Empirical
treatment is with broad-spectrum agents (e.g. piperacillin– Acute diarrhoea (p. 783), sometimes with vomiting, is the
tazobactam plus clindamycin; meropenem with clindamycin). predominant symptom in infective gastroenteritis (Box 11.10).
Ceftazidime or ciprofloxacin with doxycycline may be used Acute diarrhoea may also be a symptom of other infectious and
where marine exposure is a factor, and antifungals for suspected non-infectious diseases (Box 11.11). Stress, whether psychological
fungal necrotising fasciitis, but it is important to combine these or physical, can also produce loose stools.
with effective coverage against streptococcal infection. MRSA- The World Health Organisation (WHO) estimates that there are
associated necrotising fasciitis has emerged in some regions more than 1.7 billion cases of acute diarrhoea annually globally,
and in these places appropriate therapy for MRSA, such as a with 760 000 deaths in children under 5. In developed countries,
glycopeptide or linezolid, should be added to the empirical regimen diarrhoea remains an important problem, with the elderly being
until microbiological results allow narrowing of the antimicrobial most vulnerable (Box 11.12). The majority of episodes are due to
spectrum. Hyperbaric oxygen therapy may be considered for infections spread by the faecal–oral route and transmitted either
polymicrobial infection. Group A streptococcal infection is treated on fomites, on contaminated hands, or in food or water. Measures
with benzylpenicillin plus clindamycin, and often immunoglobulin, such as the provision of clean drinking water, appropriate disposal
though to date clinical trials have not provided clear evidence of human and animal sewage, and the application of simple
of the benefit of immunoglobulin. principles of food hygiene can all limit gastroenteritis.
The clinical features of food-borne gastroenteritis vary. Some
Gas gangrene organisms (Bacillus cereus, Staph. aureus and Vibrio cholerae)
Although Clostridium spp. may colonise or contaminate wounds, elute exotoxins that cause vomiting and/or so-called ‘secretory’
no action is required unless there is evidence of spreading diarrhoea (watery diarrhoea without blood or faecal leucocytes,
228 • INFECTIOUS DISEASE

reflecting small bowel dysfunction). In general, the time from

11.10 Causes of infectious gastroenteritis ingestion to the onset of symptoms is short and, other than
dehydration, little systemic upset occurs. Other organisms, such
Toxin in food: < 6 hrs incubation
as Shigella spp., Campylobacter spp. and enterohaemorrhagic
• Bacillus cereus (p. 262) • Clostridium spp. enterotoxin Escherichia coli (EHEC), may directly invade the mucosa of
• Staphylococcus aureus (p. 262) (p. 262) the small bowel or produce cytotoxins that cause mucosal
Bacterial: 12–72 hrs incubation ulceration, typically affecting the terminal small bowel and colon.
• Enterotoxigenic Escherichia • Vibrio cholerae (p. 264) The incubation period is longer and more systemic upset occurs,
coli (ETEC, p. 263) • Salmonella (p. 262) with prolonged bloody diarrhoea. Salmonella spp. are capable of
• Shiga toxin-producing E. coli • Shigella * (p. 265) invading enterocytes and of causing both a secretory response
(EHEC, p. 263)* • Campylobacter * (p. 262) and invasive disease with systemic features. This is seen with
• Enteroinvasive E. coli (EIEC, • Clostridium difficile * (p. 264) Salmonella Typhi and Salmonella Paratyphi (enteric fever), but
p. 263)* may occasionally be seen with other non-typhoidal Salmonella
Viral: short incubation spp., particularly in the immunocompromised host and the elderly.
• Rotavirus (p. 249) • Norovirus (p. 249)
Clinical assessment
Protozoal: long incubation
The history should address foods ingested (Box 11.13), duration
• Giardiasis (p. 287) • Microsporidiosis (p. 317) and frequency of diarrhoea, presence of blood or steatorrhoea,
• Cryptosporidiosis (pp. 287 • Amoebic dysentery (p. 286)* abdominal pain and tenesmus, and whether other people have
and 317) • Cystoisosporiasis (p. 233)
been affected. Fever and bloody diarrhoea suggest an invasive,
*Associated with bloody diarrhoea. colitic, dysenteric process. An incubation period of less than 18
hours suggests toxin-mediated food poisoning, and longer than
5 days suggests diarrhoea caused by protozoa or helminths.
Person-to-person spread suggests certain infections, such as
11.11 Differential diagnosis of acute diarrhoea shigellosis or cholera.
and vomiting
Examination includes assessment of the degree of dehydration.
Infectious causes Assessment for early signs of hypotension, such as thirst,
• Gastroenteritis • Meningococcaemia (p. 1119) headache, altered skin turgor, dry mucous membranes and
• Clostridium difficile infection • Pneumonia (especially postural hypotension, is important, particularly in tropical regions
(p. 264) ‘atypical disease’, p. 582) where dehydration progresses rapidly. Signs of more marked
• Acute diverticulitis (p. 833) • Malaria (p. 273) dehydration include supine hypotension and tachycardia,
• Sepsis (p. 196) decreased urinary output, delirium and sunken eyes. The blood
• Pelvic inflammatory disease
pressure, pulse rate, urine output and ongoing stool losses
(p. 336)
should be monitored closely.
Non-infectious causes
Gastrointestinal
• Inflammatory bowel disease • Overflow from constipation 11.13 Foods associated with infectious illness,
(p. 813) (p. 834) including gastroenteritis
• Bowel malignancy (p. 827) • Enteral tube feeding
Raw seafood
Metabolic
• Diabetic ketoacidosis (p. 735) • Neuro-endocrine tumours • Norovirus • Hepatitis A
• Thyrotoxicosis (p. 635) releasing (e.g.) VIP or 5-HT • Vibrio spp.
• Uraemia (p. 414) Raw eggs
Drugs and toxins • Salmonella serovars
• NSAIDs • Heavy metals
• Cytotoxic agents • Ciguatera fish poisoning Undercooked meat or poultry
• Antibiotics (p. 149) • Salmonella serovars • Hepatitis E (pork products)
• Proton pump inhibitors • Scombrotoxic fish poisoning • Campylobacter spp. • Clostridium perfringens
• Dinoflagellates (p. 149) (p. 150) • EHEC
• Plant toxins (p. 150)
Unpasteurised milk or juice
(5-HT = 5-hydroxytryptamine, serotonin; NSAIDs = non-steroidal anti- • Salmonella serovars. • EHEC
inflammatory drugs; VIP = vasoactive intestinal peptide) • Campylobacter spp. • Yersinia enterocolitica
Unpasteurised soft cheeses
• Salmonella serovars • Yersinia enterocolitica
• Campylobacter spp. • Listeria monocytogenes
11.12 Infectious diarrhoea in old age • ETEC
• Incidence: not increased but the impact is greater. Home-made canned goods
• Mortality: most deaths due to gastroenteritis in the developed world • Clostridium botulinum
are in adults aged over 70. Most are presumed to be caused by
dehydration leading to organ failure. Raw hot dogs, pâté
• Clostridium difficile infection (CDI): more common, especially in • Listeria monocytogenes
hospital and nursing home settings, usually following antibiotic
exposure. (EHEC = enterohaemorrhagic Escherichia coli ; ETEC = enterotoxigenic E. coli )
 Presenting problems in infectious diseases • 229

infection, particularly if the clinical features suggest a syndrome

Separate hard other than gastroenteritis.
Type 1 lumps, like nuts
(hard to pass) Management
All patients with acute, potentially infective diarrhoea should be
appropriately isolated to minimise person-to-person spread of
Sausage-shaped infection. If the history suggests a food-borne source, public
Type 2 but lumpy
health measures must be implemented to identify the source
and to establish whether other linked cases exist (p. 114).

Fluid replacement
Like a sausage but Replacement of fluid losses in diarrhoeal illness is crucial and
Type 3 with cracks on its
surface may be life-saving.
Although normal daily fluid intake in an adult is only 1–2 L,
there is considerable additional fluid movement in and out of the
gut in secretions (see Fig. 21.7, p. 769). Altered gut resorption
Like a sausage or
snake, smooth with diarrhoea can result in substantial fluid loss; for example,
Type 4
and soft 10–20 L of fluid may be lost in 24 hours in cholera. The fluid
lost in diarrhoea is isotonic, so both water and electrolytes need
to be replaced. Absorption of electrolytes from the gut is an
Soft blobs with active process requiring energy. Infected mucosa is capable
11
Type 5 clear-cut edges of very rapid fluid and electrolyte transport if carbohydrate is
(passed easily) available as an energy source. Oral rehydration solutions (ORS)
therefore contain sugars, as well as water and electrolytes (Box
11.14). ORS can be just as effective as intravenous replacement
Fluffy pieces with fluid, even in the management of cholera. In mild to moderate
Type 6 ragged edges, a gastroenteritis, adults should be encouraged to drink fluids
mushy stool and, if possible, continue normal dietary food intake. If this is
impossible – due to vomiting, for example – intravenous fluid
administration will be required. In very sick patients or those with
Watery, no solid cardiac or renal disease, monitoring of urine output and central
Type 7 pieces venous pressure may be necessary.
Entirely liquid
The volume of fluid replacement required should be estimated
based on the following considerations:
• Replacement of established deficit. After 48 hours of
Fig. 11.5 Bristol stool chart. The stool is given a ‘score’ of 1–7 by
reference to the verbal and visual description. This is recorded on a chart moderate diarrhoea (6–10 stools per 24 hrs), the average
(usually known as a ‘Bristol stool chart’) or in a patient monitoring adult will be 2–4 L depleted from diarrhoea alone.
database. Adapted from Lewis SJ, Heaton KW. Stool form scale as a Associated vomiting will compound this. Adults with this
useful guide to intestinal transit time. Scand J Gastroenterol 1997; symptomatology should therefore be given rapid
32:920–924. replacement of 1–1.5 L, either orally (ORS) or by
intravenous infusion (normal saline), within the first 2–4
hours of presentation. Longer symptomatology or more
The severity of diarrhoea may be assessed by reference to persistent/severe diarrhoea rapidly produces fluid losses
the Bristol stool form scale (Bristol stool chart), which allows comparable to diabetic ketoacidosis and is a metabolic
an objective assessment of stool consistency by providing a emergency requiring active intervention.
verbal and visual reference scale (Fig. 11.5). The Bristol stool
form scale was developed in the 1990s to monitor patients
with irritable bowel syndrome, but its main use (at least in UK
hospitals) is to monitor hospital inpatients with loose stool to 11.14 Composition of oral rehydration solution and
assist in decisions on stool sampling and infection prevention other replacement fluids*
precautions, especially in relation to C. difficile. Fluid Na K Cl Energy

Investigations WHO 90 20 80 54

These include stool inspection for blood and microscopy for Dioralyte 60 20 60 71
leucocytes, and also an examination for ova, cysts and parasites Pepsi 6.5 0.8 – 400
if the history indicates residence or travel to areas where these 7UP 7.5 0.2 – 320
infections are prevalent. Stool culture should be performed and
Apple juice 0.4 26 – 480
C. difficile toxin sought. FBC and serum electrolytes indicate
the degree of inflammation and dehydration. Where cholera is Orange juice 0.2 49 – 400
prevalent, examination of a wet film with dark-field microscopy Breast milk 22 36 28 670
for darting motility may provide a diagnosis. In a malarious area,
*Values given in mmol/L for electrolyte and kcal/L for energy components.
a blood film for malaria parasites should be obtained. Blood and
(WHO = World Health Organisation)
urine cultures and a chest X-ray may identify alternative sites of
230 • INFECTIOUS DISEASE

• Replacement of ongoing losses. The average adult’s 11.15 How to assess health needs in travellers
diarrhoeal stool accounts for a loss of 200 mL of isotonic before departure*
fluid. Stool losses should be carefully charted and an
• Destination
estimate of ongoing replacement fluid calculated.
• Personal details, including previous travel experience
Commercially available rehydration sachets are
• Dates of trip
conveniently produced to provide 200 mL of ORS; one • Itinerary and purpose of trip
sachet per diarrhoea stool is an appropriate estimate of • Personal medical history, including pregnancy, medication and
supplementary replacement requirements. allergies (e.g. to eggs, vaccines, antibiotics)
• Replacement of normal daily requirement. The average • Past vaccinations:
adult has a daily requirement of 1–1.5 L of fluid in addition Childhood schedule followed? Diphtheria, tetanus, pertussis,
to the calculations above. This will be increased polio, Neisseria meningitidis types B/C, Haemophilus influenzae
substantially in fever or a hot environment. B (HiB)
Travel-related? Typhoid, yellow fever, hepatitis A, hepatitis B,
Antimicrobial agents meningococcal ACW135Y, rabies, Japanese B encephalitis,
tick-borne encephalitis
In non-specific gastroenteritis, routine use of antimicrobials does
• Malaria prophylaxis: questions influencing the choice of antimalarial
not improve outcome and may lead to antimicrobial resistance drugs are destination, past experience with antimalarials, history of
or side-effects. They are usually used where there is systemic epilepsy or psychiatric illness
involvement, a host with immunocompromise or significant
comorbidity. *Further information is available at fitfortravel.nhs.uk.
Evidence suggests that, in EHEC infections, the use of
antibiotics may make the complication of haemolytic uraemic
syndrome (HUS; p. 408) more likely due to increased toxin
release. Antibiotics should therefore not be used in this condition. that the pattern of infectious diseases seen in each country
Conversely, antibiotics are indicated in Shigella dysenteriae changes constantly, and travel history and information on countries
infection and in invasive salmonellosis – in particular, typhoid previously lived in, particularly during childhood, are crucial.
fever. Antibiotics may also be advantageous in cholera epidemics, In general, the diversity of infectious diseases is greater in
reducing infectivity and controlling the spread of infection. tropical than in temperate countries, and people in temperate
countries have immunity to a narrower range of infections,
Antidiarrhoeal, antimotility and antisecretory agents reflecting less exposure in childhood and less ongoing boosting of
These agents are not usually recommended in acute infective immunity later in life, so that the most common travel-associated
diarrhoea. Loperamide, diphenoxylate and opiates are potentially infections are those that are acquired by residents of temperate
dangerous in dysentery in childhood, causing intussusception. countries during visits to the tropics. In addition, those who
Antisecretory agents, such as bismuth and chlorpromazine, may have lived in tropical areas may lose immunity when they move
make the stools appear more bulky but do not reduce stool fluid to temperate countries and become susceptible when visiting
losses and may cause significant sedation. Adsorbents, such their homeland.
as kaolin or charcoal, have little effect. Most travel-associated infections can be prevented. Pre-
travel advice is tailored to the destination and the traveller (Box
Non-infectious causes of food poisoning 11.15). It includes avoidance of insect bites (using at least 20%
diethyltoluamide (DEET)), sun protection (sunscreen with a sun
While acute food poisoning and gastroenteritis are most frequently protection factor (SPF) of at least 15), food and water hygiene
caused by infections, non-infectious causes must also be (‘Boil it, cook it, peel it or forget it!’), how to respond to travellers’
considered in the differential diagnosis. These are discussed diarrhoea (seek medical advice if bloody or if it lasts more than
on page 149. 48 hrs) and, if relevant, safe sex (condom use).

Antimicrobial-associated diarrhoea Fever acquired in the tropics

Antimicrobial-associated diarrhoea (AAD) is a common Presentation with unexplained fever is common in travellers
complication of antimicrobial therapy, especially with broad- who are visiting or have recently travelled to tropical areas.
spectrum agents. It is most common in the elderly but can Fever may also occur in those living in tropical regions if they
occur at all ages. Although the specific mechanism is unknown have not developed immunity to the endemic pathogen or if
in most cases of AAD, C. difficile (p. 264) is implicated in 20–25% this immunity is compromised by factors such as pregnancy.
of cases and is the most common cause among patients with Frequent final diagnoses in such patients are malaria, typhoid
evidence of colitis. C. perfringens is a rarer cause that usually fever, viral hepatitis and dengue fever. Travellers to affected areas
remains undiagnosed, and Klebsiella oxytoca may also cause may have viral haemorrhagic fevers (VHFs) such as Ebola, Lassa,
antibiotic-associated haemorrhagic colitis. Crimean–Congo and Marburg (see Box 11.36, p. 245), avian
influenza (H5N1) or Middle East respiratory syndrome (MERS),
Infections acquired in the tropics which require special isolation precautions.

Recent decades have seen unprecedented increases in long- Clinical assessment

distance business and holiday travel, as well as extensive The approach to unexplained fever is as described above and
migration. Although certain diseases retain their relatively fixed key questions relating to infections acquired in tropical regions
geographical distribution, being dependent on specific vectors are listed in Box 11.16. Medicines purchased in some countries
or weather conditions, many travel with their human hosts and may have reduced efficacy, e.g. for malaria prophylaxis. Consult
some may then be transmitted to other people. This means reliable up-to-date sources about resistance to antimalarial drugs