Infectious disease

Infectious disease

D.H. Dockrell

S. Sundar

B.J. Angus

R.P. Hobson

Clinical examination of patients with infectious disease



• Documentation of fever. ‘Feeling hot’ or sweaty does not necessarily signify fever. Fever is diagnosed only when a body temperature of over 38.0°C has been recorded. Axillary and aural measurement is less accurate than oral or rectal. Outpatients may be trained to keep a temperature chart.

• Rigors. Shivering (followed by excessive sweating) occurs with a rapid rise in body temperature from any cause.

• Night sweats. These are associated with particular infections (e.g. tuberculosis, infective endocarditis), but sweating from any cause is worse at night.

• Excessive sweating. Alcohol, anxiety, thyrotoxicosis, diabetes mellitus, acromegaly, lymphoma and excessive environmental heat all cause sweating without temperature elevation.

• Recurrent fever. There are various causes, e.g. Borrelia recurrentis, bacterial abscess.

• Accompanying features. Headache. Severe headache and photophobia, although characteristic of meningitis, may accompany other infections. Delirium. Mental confusion during fever is more common in young children or the elderly. Muscle pain. Myalgia may occur with viral infections, such as influenza, and with septicaemia, including meningococcal sepsis. Shock. Shock may accompany severe infections and sepsis (Ch. 8).

image History-taking in suspected infectious disease*

Sexual history

• Explore in a confidential and non-threatening way (Ch. 15); remember that the most common mechanism of HIV-1 transmission is heterosexual contact (Ch. 14)

*Always consider non-infectious aetiologies in the differential diagnosis.

The principles of infection and its investigation and therapy are described in Chapter 6. This chapter and the following ones on human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and sexually transmitted infection (STI) describe the approach to patients with potential infectious disease, the individual infections and the resulting syndromes.

Presenting problems in infectious diseases

Infectious diseases present with myriad clinical manifestations. Many of these are described either in other chapters of this book or below.


‘Fever’ implies an elevated core body temperature of more than 38.0°C (p. 138). Fever is a response to cytokines and acute phase proteins (pp. 74 and 82) and occurs in infections and in non-infectious conditions.

Clinical assessment

The differential diagnosis is very broad so clinical features are used to guide the most appropriate investigations. The systematic approach described on pages 294–295 should be followed. Box 13.1 describes the assessment of elderly patients.


If the clinical features do not suggest a specific infection, then initial investigations should include:

Subsequent investigations in patients with HIV-related (p. 396), immune-deficient (p. 301), nosocomial or travel-related (p. 309) pyrexia and in individuals with associated symptoms or signs of involvement of the respiratory, gastrointestinal or neurological systems are described elsewhere.

Fever with localising symptoms or signs

In most patients, the site of infection is apparent after clinical evaluation (p. 294), and the likelihood of infection is reinforced by investigation results (e.g. neutrophilia with raised ESR and CRP in bacterial infections). Not all apparently localising symptoms are reliable, however; headache, breathlessness and diarrhoea can occur in sepsis without localised infection in the central nervous system (CNS), respiratory tract or gastrointestinal tract. Careful interpretation of the clinical features is vital (e.g. severe headache associated with photophobia, rash and neck stiffness suggests meningitis, whereas moderate headache with cough and rhinorrhoea is consistent with a viral upper respiratory tract infection).

Common infections that present with fever are shown in Figure 13.1. Further investigation and management are specific to the cause, but may include empirical antimicrobial therapy (p. 149) pending confirmation of the microbiological diagnosis.

Pyrexia of unknown origin

Pyrexia of unknown origin (PUO) is defined as a temperature persistently above 38.0°C for more than 3 weeks, without diagnosis, despite initial investigation during 3 days of inpatient care or after more than two outpatient visits. Subsets of PUO are described by medical setting: HIV-1 related, immune-deficient or nosocomial. Up to one-third of cases of PUO remain undiagnosed.

Clinical assessment

Major causes of PUO are outlined in Box 13.2. Rare causes, such as periodic fever syndromes (p. 85), should be considered in those with a positive family history. Children and younger adults are more likely to have infectious causes – in particular, viral infections. Older adults are more likely to have certain infectious and non-infectious causes (see Box 13.1). Detailed history and examination should be repeated at regular intervals to detect emerging features (e.g. rashes, signs of infective endocarditis (p. 625) or features of vasculitis). In men, the prostate should be considered as a potential source of infection.

image 13.2   Aetiology of pyrexia of unknown origin (PUO)

Infections (~30%)

Specific locations

Specific organisms

Specific patient groups

Malignancy (~20%)

Connective tissue disorders (~15%)

Miscellaneous (~20%)







Drug reactions*

Factitious fever

Idiopathic (~15%)

*Most common causes within each group.

Clinicians should be alert to the possibility of factitious fever, in which high temperature recordings are engineered by the patient (Box 13.3).


If initial investigation of fever (see above) is negative, a series of further microbiological and non-microbiological investigations should be considered (Boxes 13.4 and 13.5). These will usually include:

image 13.4   Microbiological investigation of PUO

Lesions identified on imaging should usually be biopsied in order to seek evidence of relevant pathogens by culture, histopathology or nucleic acid detection. The chance of a successful diagnosis is greatest if procedures for obtaining and transporting the correct samples in the appropriate media are carefully planned in advance; this requires discussion between the clinical team, the radiologist or surgeon performing the procedure, and the local microbiologist and histopathologist. Liver biopsy may be justified, e.g. to identify idiopathic granulomatous hepatitis, if there are biochemical or radiological abnormalities. Bone marrow biopsies have a diagnostic yield of up to 15%, most often revealing haematological malignancy, myelodysplasia or tuberculosis, and also identifying brucellosis, typhoid fever or visceral leishmaniasis. Bone marrow should be sent for culture, as well as microscopy. Laparoscopy is occasionally undertaken with biopsy of abnormal tissues. Splenic aspiration in specialist centres is the diagnostic test of choice for suspected visceral leishmaniasis. Temporal artery biopsy should be considered in patients over the age of 50 years, even in the absence of physical signs or a raised ESR. ‘Blind’ biopsy of other structures in the absence of localising signs, or laboratory or radiology results is unhelpful.

Fever in the injection drug-user

Intravenous injection of recreational drugs is widespread in many parts of the world (p. 240). Infective organisms are introduced by non-sterile (often shared) injection equipment (Fig. 13.2), and infection is facilitated by immunodeficiency due to malnutrition or the toxic effects of drugs. The risks increase with prolonged drug use and injection into large veins of the groin and neck because of progressive thrombosis of superficial peripheral veins. The most common causes of fever are soft tissue or respiratory infections.

Fig. 13.2 Fever in the injection drug-user: key features of clinical examination.
Full examination (p. 294) is required but features most common amongst injection drug-users are shown here. (DVT = deep venous thrombosis; JVP = jugular venous pulse)

Clinical assessment

The history should address the following risk factors:

• Site of injection. Femoral vein injection is associated with vascular complications such as deep venous thrombosis (50% of which are septic) and accidental arterial injection with false aneurysm formation or a compartment syndrome due to swelling within the fascial sheath. Local complications include ilio-psoas abscess, and septic arthritis of the hip joint or sacroiliac joint. Injection of the jugular vein can be associated with cerebrovascular complications. Subcutaneous and intramuscular injection has been related to infection by clostridial species, the spores of which contaminate heroin. Clostridium novyi causes a local lesion with significant toxin production, leading to shock and multi-organ failure. Tetanus, wound botulism and gas gangrene also occur.

• Technical details of injection. Sharing of needles and other injecting paraphernalia (including spoons and filters) greatly increases the risk of blood-borne virus infection (e.g. HIV-1, hepatitis B or C virus). Some users lubricate their needles by licking them prior to injection, thus introducing mouth organisms (e.g. anaerobic streptococci, Fusobacterium spp. and Prevotella spp). Contamination of commercially available lemon juice, used to dissolve heroin before injection, has been associated with blood-stream infection with Candida spp.

• Substances injected. Injection of cocaine is associated with a variety of vascular complications. Certain formulations of heroin have been linked with particular infections, e.g. wound botulism with black tar heroin. Drugs are often mixed with other substances, e.g. talc.

• Blood-borne virus status. Results of previous HIV-1 and hepatitis virus tests or vaccinations for hepatitis viruses should be recorded.

• Surreptitious use of antimicrobials. Addicts may use antimicrobials to self-treat infections, masking initial blood culture results.

Key findings on clinical examination are shown in Figure 13.2. It can be difficult to distinguish the effects of infection from the effects of drugs or drug withdrawal (excitement, tachycardia, sweating, marked myalgia, confusion). Stupor and delirium may result from drug administration but may also indicate meningitis or encephalitis. Non-infected venous thromboembolism is also common in this group.


The initial investigations are as for any fever (see above), including a chest X-ray and blood cultures. Since blood sampling may be difficult, contamination is often a problem. Echocardiography to detect infective endocarditis should be performed in all injection drug-users with: bacteraemia due to Staphylococcus aureus or other organisms associated with endocarditis (Fig. 13.3A); thromboembolic phenomena; or a new or previously undocumented murmur. Endovascular infection should also be suspected if lung abscesses or pneumatocoeles are detected radiologically. Additional imaging should be focused on sites of injection or of localising symptoms and signs (Fig. 13.3B). Any pathological fluid collections should be sampled.

Urinary toxicology tests may suggest a non-infectious cause of the presenting complaint. While being investigated, all injection drug-users should be offered testing for infection with hepatitis B and C virus and HIV-1.

Microbiological results are crucial in guiding therapy. Injection drug-users may have more than one infection. Skin and soft tissue infections are most often due to Staph. aureus or streptococci, and sometimes to Clostridium spp. or anaerobes. Pulmonary infections are most often due to the common pathogens causing community-acquired pneumonia, tuberculosis or septic emboli (Fig. 13.3C). Endocarditis with septic emboli commonly involves Staph. aureus and viridans streptococci, but Pseudomonas aeruginosa and Candida spp. are also encountered.


Empirical therapy of fever in the injection drug-user includes an antistaphylococcal penicillin (e.g. flucloxacillin) or, if meticillin-resistant Staph. aureus (MRSA) is prevalent in the community, a glycopeptide (e.g. vancomycin). Once a particular pathogen is identified, specific therapy is commenced, with modification when antimicrobial susceptibility is available. In injection drug-users, right-sided endocarditis due to Staph. aureus is customarily treated with high-dose intravenous flucloxacillin. In left-sided Staph. aureus endocarditis, aminoglycoside therapy may be added. Right-sided endocarditis caused by MRSA is usually treated with 4 weeks of vancomycin plus gentamicin for the first week. Specialist advice should be sought.

For localised infections of the skin and soft tissues, oral therapy with agents active against staphylococci, streptococci and anaerobes is appropriate (e.g. flucloxacillin plus co-amoxiclav or clindamycin). Non-adherence with prescribed antimicrobial regimens leads to a high rate of relapse for all infections in this patient group.

Fever in the immunocompromised host

Immunocompromised hosts include those with congenital immunodeficiency (p. 78), HIV infection (Ch. 14) and iatrogenic immunosuppression induced by chemotherapy (p. 276), transplantation (p. 95) or immunosuppressant medicines, including high-dose corticosteroids. Metabolic abnormalities, such as under-nutrition or hyperglycaemia, may also contribute. Multiple elements of the immune system are potentially compromised. A patient may have impaired neutrophil function from chemotherapy, impaired T-cell and/or B-cell responses due to underlying malignancy, T-cell and phagocytosis defects due to corticosteroids, mucositis from chemotherapy and an impaired skin barrier due to insertion of a central venous catheter.

Fever may result from infectious or from non-infectious causes, including drugs, vasculitis, neoplasm, organising pneumonitis, lymphoproliferative disease, graft-versus-host disease (in recipients of haematopoietic stem cell transplants; p. 1017) or Sweet’s syndrome (reddish nodules or plaques with fever and leucocytosis, in association with haematological malignancy).

Clinical assessment

The following should be addressed in the history:

Examination should include inspection of the normal physical barriers provided by skin and mucosal surfaces and, in particular, central venous catheters, the mouth, sinuses, ears and perianal area (digital rectal examination should be avoided). Disseminated infections can manifest as cutaneous lesions. The areas around fingernails and toenails should also be inspected closely.


Initial screening tests are as described above (p. 296). Immunocompromised hosts often have decreased inflammatory responses leading to attenuation of physical signs, such as neck stiffness with meningitis, radiological features and laboratory findings, such as leucocytosis. Chest CT scan should be considered in addition to chest X-ray when respiratory symptoms occur. Abdominal imaging may also be warranted, particularly if there is right lower quadrant pain, which may indicate typhlitis (inflammation of the caecum) in neutropenic patients. Blood cultures from a central venous catheter, urine cultures, and stool cultures if diarrhoea is present are also recommended.

Nasopharyngeal aspirates are sometimes diagnostic, as immunocompromised hosts may shed respiratory viruses for prolonged periods. Skin lesions should be biopsied if nodules are present, and investigation should include fungal stains. Useful molecular techniques include polymerase chain reaction (PCR) for CMV and Aspergillus spp. DNA, and antigen assays (e.g. cryptococcal antigen (CrAg) for Cryptococcus neoformans, and galactomannan for Aspergillus spp. in blood or Legionella pneumophila type 1 in urine). Antibody detection is rarely useful in immunocompromised patients. Patients with respiratory signs or symptoms should be considered for bronchoscopy in order to obtain bronchoalveolar lavage fluid to detect pathogens, including Pneumocystis jirovecii (carinii), as well as bacteria, fungi and viruses.

Neutropenic fever

Neutropenic fever is strictly defined as a neutrophil count of less than 0.5 × 109/L (p. 1004) and a single axillary temperature above 38.5°C or three recordings above 38.0°C over a 12-hour period, although the infection risk increases progressively as the neutrophil count drops below 1.0 × 109/L. Patients with neutropenia are particularly prone to bacterial or fungal infection. Gram-positive organisms are the most common pathogens, particularly in association with in-dwelling catheters.

Empirical broad-spectrum antimicrobial therapy is commenced as soon as neutropenic fever occurs and cultures have been obtained. The most common regimens for neutropenic sepsis are broad-spectrum penicillins, such as piperacillin–tazobactam IV. Although aminoglycosides are commonly used in combination, routine use is not supported by trial data (Box 13.6). If fever has not resolved after 3–5 days, empirical antifungal therapy (e.g. caspofungin) is added (p. 159). An alternative antifungal strategy is to use azole prophylaxis in high-risk patients and markers of early fungal infection, such as galactomannan antigen, to guide initiation of antifungal treatment (a ‘pre-emptive approach’).

Post-transplantation fever

Fever in transplant recipients may be due to infection, episodes of graft rejection in solid organ transplant recipients, or graft-versus-host disease following haematopoietic stem cell transplantation (HSCT; p. 1017).

Infections in solid transplant recipients are grouped according to the time of onset (Box 13.7). Those in the first month are related to the underlying condition or surgical complications. Those occurring 1–6 months after transplantation are characteristic of impaired T-cell function. Risk factors for CMV infection have been identified and patients commonly receive either prophylaxis or intensive monitoring involving regular testing for CMV DNA by PCR and early initiation of anti-CMV therapy using intravenous ganciclovir or oral valganciclovir if tests become positive.

Apr 9, 2017 | Posted by in GENERAL SURGERY | Comments Off on Infectious disease

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