28th July 2023

Bacterial Infections

Respiratory Tract Infections

Respiratory tract infections are a major cause of morbidity and mortality worldwide. The exact microbiological aetiology is often not identified when treating patients and may include both viral and bacterial pathogens. Infection can manifest at all parts of the respiratory tract, from the nose down to the lungs. Most hospitalisation in adults is due to pneumonia (infection within the lung itself) or exacerbations of obstructive airway disease such as asthma or COPD. These will therefore be the focus of this topic.

The British Thoracic Society (BTS) provides clear guidance for managing pneumonia, which is used to inform NICE guidance. The key principles are as follows:

• Assess severity
• Conduct microbiological testing to identify the pathogen
• Initiate treatment with empirical antibiotics when bacterial pneumonia is suspected, to be narrowed if a specific pathogen is identified

Assessment and diagnosis

Severity is assessed using the CURB-65 score, with 1 point given for each of the following:

• C = confusion
• U = urea > 7 mmol/L
• R = RR ≥ 30/min
• B = BP < 90 mmHg or ≤ 60 mmHg
• 65 = age more than 65

0-1 = outpatient management, 2 = admission, 3+ = admission and consider ITU escalation.

Investigations include routine bloods such as FBC, U&Es, LTT, and CRP; blood cultures; sputum cultures, throat swab for respiratory viruses; urinary antigens; chest x-ray.

Diagnosis is made on the basis of characteristic clinical features with evidence of consolidation in the lung (i.e. auscultation findings of ‘crackles’ or radiological confirmation on chest x-ray.

The most common pathogen causing respiratory illness is Streptococcus pneumoniae. Other common causes of community acquired infection include Haemophilus influenzae and Moraxella catarrhalis, which are particularly associated with patients with COPD.

Different pathogens are implicated in different age groups, particularly paediatric respiratory tract infections, which are associated with numerous causative organisms that rarely affect adults. Children often present with upper respiratory tract infection, caused by either viruses or bacteria. This is not the focus of this topic, but a comprehensive summary can be found in the References section.

Management

The first line treatment in the community is monotherapy with amoxicillin (erythromycin if penicillin allergic). If the patient is suspected of having an infective COPD exacerbation, then doxycycline is generally the preferred first line. COPD patients should also be supported with a 5-7 day oral steroids course and may require acute nebulisers.

For those requiring hospital admission, the first line is a broad-spectrum antibiotic, such co amoxiclav or ceftriaxone, with clarithromycin generally also given as cover for atypical infections, with doxycycline or levofloxacin as alternatives.

Exact guidance varies per area, so it is important to consult local guidelines. The treatment should be appropriately tailored if sensitivities indicate a more appropriate antibiotic.

Atypical pneumonia

There are some important so-called ‘atypical’ causes of pneumonia. These may cause a different clinical syndrome or not respond to initial antibiotic treatment. These include:

• Mycoplasma pneumoniae characteristically causes bilateral pneumonia and is associated with neurological and dermatological complications.
• Legionella pneumophila, a spirochete found in water coolant systems such as air conditioners, is often associated with travel to hot countries. Legionnaires’ disease can cause transaminitis, hyponatremia and neurological features. It is difficult to diagnose as it does not grow on standard cultures; if suspected, urinary antigens should be tested as these are the most reliable investigation.
• Chlamydophila psittaci, a rare pathogen transmitted from close contact with birds, typically causing myalgia, headache and a dry cough.

Gastrointestinal Infections

The most common manifestation of bacterial gastrointestinal infections is gastroenteritis, which typically presents with vomiting and diarrhoea (often bloody), associated with abdominal pain and variable systemic upset. The incubation period varies depending on the pathogen, but generally, symptoms present within 24-48 hours of exposure. Many infections are due to contaminated food, and these then spread rapidly person-to-person through faeco-oral spread.

More detail on this topic can be found in Bowel Infection and Inflammation.

Aetiology

The most common cause of gastroenteritis in the UK is Campylobacter species. They generally contaminate chicken, with poor food hygiene increasing the risk of infection. Barbecues are a common ‘exposure’ event, often seen in MRCP questions.

Salmonella food poisoning is another important cause of gastroenteritis. Cases have decreased after a successful vaccination campaign, but it may still cause outbreaks which are often related to specific venues with catered food, such as weddings. Salmonella species are an important cause of septic arthritis in sickle cell patients.

Typhoid, or enteric fever, is an important Salmonella complication, most associated with the typhi and paratyphi species. High fever, relative bradycardia and rose spots are classical findings.

Bacillus cereus is said to have a short incubation period of only a few hours and classically comes from reheating rice, with vomiting a key feature.

There are four species of Shigella – two endemic in the UK in S. sonnei and S flexneri, and two imported in S. bodyi and S. dysenteriae. The endemic forms may be spread by sexual contact, with prevalence high in men who have sex with men. Shigellosis outbreaks have also been described in nursery settings.

Escherichia coli O157:H7, sometimes called STEC (Shiga toxin-producing Escherichia coli), is associated with animal contact. A common case scenario is farms or petting zoos. Hemolytic uraemic syndrome (HUS) is an important complication. Generally seen in children, it causes nephrotic syndrome and is associated with anaemia and thrombocytopenia. Characteristic features are vomiting, bloody diarrhoea, fever, confusion, and purpura/petechiae.

Listeria monocytogenes can affect any individual, usually causing non-specific diarrhoea and vomiting. Soft cheese, unpasteurised milk, smoked meats, and unwashed produce have all been linked to the acquisition of Listeria. Risk factors for the disease include pregnancy, extremes of age, alcohol excess and immunodeficiency. Listeria also affects sheep, where it can cause spontaneous abortion, and farmers are hence at increased risk of the disease. It is important to be aware of especially in the context of pregnancy, as Listeria can cause meningitis in neonates. For this reason, pregnant women are advised to avoid high risk foods.

Management

Most cases of acute bacterial gastroenteritis are self-limiting and do not require antibiotics. Those at the extremes of age, with prolonged symptoms, or the immunocompromised may require treatment. Ciprofloxacin is a reasonable choice of antibiotic in most cases, although there are increasing reports of resistance in imported diseases such as Shigella. Azithromycin is another option.

Whilst gastroenteritis is usually caused by an exogenous microorganism, other gastrointestinal infections are often caused by displaced bacteria from the usual GI tract flora. This is seen in biliary tract infections, such as cholecystitis, cholangitis and liver abscesses, peritonitis, and bowel perforation. As such, these infections are usually polymicrobial, and organisms such as Escherichia coli Klebsiella pneumoniae, Enterococcus and anaerobes are often found on specimen cultures. An empirical combination of cefuroxime and metronidazole is used to treat suspected intra abdominal infection until sensitivities are available.

More information about other abdominal infections, such as those of the liver, gallbladder and pancreas, can be found in the Hepatic Pathology and Pancreatico-biliary Pathology sections.

Genitourinary Infections

Urinary tract infections (UTIs)

UTIs can be classified as lower or upper. Lower urinary tract infection usually refers to cystitis, with symptoms of urinary frequency and dysuria. Upper urinary tract infection implies ascending infection in the kidneys, i.e. pyelonephritis, which typically presents with loin pain, fever, rigours, and nausea/vomiting.

Enteric bacteria are usually the cause of infection in the urinary tract, with Escherichia coli implicated in over 50% of cases. A wide range of antibiotics are used for UTIs, with choice depending on the patient’s microbiological history and local epidemiology, meaning local guidance should always be consulted.

Diagnosis is made through urinalysis, with urine samples sent for microscopy, culture and sensitivities to confirm infection and help tailor antibiotic choice. Urinalysis is not a reliable diagnostic tool in elderly patients, who should be treated based on symptoms and laboratory confirmation.

Pregnancy is a risk factor for urinary tract infections, and the antibiotic choice is limited by adverse effects on the foetus, with trimethoprim an important contraindicated antibiotic to know.

Bacteria are often found colonising the urinary tract without causing infection, known as asymptomatic bacteriuria. It is increasingly recognised that this finding does not require treatment, except in special populations such as pregnant women, men, and potentially renal transplant patients.

In men, prostatitis can cause exquisite pain on sitting or rectal examination. The same urinary pathogens cause it as UTIs but require extended treatment, usually for 14 days with ciprofloxacin.

Sexually transmitted infections (STIs)

Most STIs are caused by Chlamydia trachomatis or Neisseria gonorrhoeae. Both are Gram negative bacteria, and N. gonorrhoea is particularly notable for its diplococci morphology, which makes it distinctive in microscopy.

Both chlamydia and gonorrhoea cause a similar broad spectrum of disease, ranging from asymptomatic infection to pelvic inflammatory disease.

Diagnosis is either made on microscopy of swab smears or by a nucleic acid amplification test (NAAT).

Treatment of gonorrhoea has changed over the past few decades as resistance has emerged. Currently, ceftriaxone (1g, intramuscularly) is the treatment of choice. For chlamydia, a single dose treatment of azithromycin is the preferred treatment. Neonates may develop conjunctival disease after exposure to chlamydia in the birth canal, which is an important potential complication of chlamydia to be aware of.

Syphilis is caused by Treponema pallidum. It is one of medicine’s great mimickers and can be confused for many other diseases. It usually starts with a primary, painless ulcer (chancre) at the initial infection site, often the genitals. A secondary syphilis rash may occur a few weeks after inoculation before the bacteria enters the latent phase, which may last for decades.

If untreated, after this latency period, tertiary syphilis may develop, which can have life-threatening complications. Tertiary syphilis manifestations include aortic root disease, neurological disease, and gummatous disease of the skeleton.

Penicillin is the treatment of choice for syphilis. The dose and route depend on stage and organ involvement, summarised in the British Association for Sexual Health and HIV (BASHH) guidelines, which can be found in the References section.

Neurological Infections

Bacterial infection of the neurological system usually manifests as meningitis or encephalitis. A brief overview is given here, with more detailed information in the Neurology topics.

Meningitis

Meningitis is caused by inflammation of the meninges. Infectious causes include bacteria, viruses, and mycobacteria. It can also be caused by malignancy. This section focuses on bacterial causes.

The classical meningitis triad is headache, fever and neck stiffness. It may also cause confusion, drowsiness, and other focal neurological signs and symptoms.

The most common causative organism of acute bacterial meningitis is Neisseria meningitidis (meningococcus), followed by Streptococcus pneumoniae (pneumococcus).

Meningococcal disease is usually rapid in onset, with symptoms progressing over hours, and may present as florid sepsis with the classical non-blanching petechial rash, which is diagnostic of this bacteria. The rash indicates meningococcus rather than being a feature of all meningitis. The pneumococcal disease may be more subacute over a few days, and a purpuric rash is absent.

The investigation of choice is lumbar puncture (LP). This should ideally be done before initiating antibiotic therapy, or the results may not be accurate. Contraindications include evidence of raised intracranial pressure (as LP can cause uncal herniation in this case), coagulopathy, and a rapidly involving rash. CT is generally done prior to LP, providing there is time to rule out any intracranial mass that can cause raised intracranial pressure, and is an absolute necessity if the patient has any risk factors for a mass or any clinical features suggesting one. If arranging these investigations leads to a significant delay in treatment (i.e. more than 6 hours), antibiotics should be first commenced.

The cerebrospinal fluid analysis helps confirm acute bacterial meningitis as it should show a (very) high neutrophil count, with high protein and low glucose compared to venous blood. Microscopy may also identify the organism.

First line treatment is with intravenous ceftriaxone (or chloramphenicol if there is an allergy history to beta-lactams). Steroids are also indicated for pneumococcal disease. In a non-inpatient setting, a single dose of intramuscular benzylpenicillin is recommended as empirical treatment in suspected bacterial meningitis if there is a delay in reaching a hospital.

Tracing for prophylaxis is only required for close household contacts of Neisseria meningitidis, for instance, those who share a room or young children. Acute bacterial meningitis is a notifiable disease independent of microbiological causes.

Meningitis with Listeria monocytogenes and Mycobacterium tuberculosis can cause lymphocytosis rather than neutrophilia on CSF analysis. Listeria causes invasive disease in groups with a risk factor, as outlined in the Gastrointestinal Infections section. Treatment is with high dose amoxicillin (or co-trimoxazole if penicillin allergic).

Encephalitis

Encephalitis refers to the inflammation of the brain (i.e. cerebrum or cortex). It presents with a clinical syndrome of headache, fever, focal neurological deficits, and seizures, with the latter being more common than in meningitis.

It is most commonly viral in the UK, with herpes simplex virus (HSV) type 1 being the most common causative organism. The same pathogens which cause bacterial meningitis may also cause bacterial encephalitis.

Meningitis and encephalitis share symptoms, and there may be an overlap between the two; encephalitis is therefore managed in much the same way as meningitis. The key points are prompt diagnosis with CSF analysis and prompt initiation of treatment. As HSV is the most common cause in the UK, empirical treatment of encephalitis includes the antiviral drug aciclovir until the causative organism is identified.

Cerebral abscesses

Abscesses in the brain generally arise secondary to infections, such as otitis media, mastoiditis or sinus infection. They may also result from facial or head trauma, including surgery and implantation of foreign bodies, or due to trauma. The most common causative organisms are Staphylococcus and Streptococci species.

Cerebral abscesses generally present predominantly with a severe headache and often have a subacute presentation of 1-2 weeks. Fever, confusion, drowsiness, focal neurological deficits and seizures may also be seen. There may be localised pain at the site of the abscess.

Imaging findings vary depending on the stage of the disease. The characteristic finding is a ring-enhancing solitary lesion on CT. MRI is more accurate and can be used to further characterise the lesion following CT.

A brain abscess is a medical emergency. The risk of raised intracranial pressures necessitates urgent neurosurgical referral. Antibiotic treatment is similar to the approach taken in meningitis and should be tailored as per sensitivities whenever possible.

Cardiovascular Infections

Infections of the cardiovascular system are rare. The most commonly seen in medicine are endocarditis and septic thrombophlebitis.

Infective endocarditis

Endocarditis refers to any infection of the endocardial lining of the heart, i.e. the endocardium. It most commonly affects valvular tissues. It is associated with a high degree of morbidity and mortality rate. Endocardial infections lead to bacteraemia, and a hallmark is, therefore, positive blood culture.

Many organisms can cause infective endocarditis, with the commonest being Gram positive bacteria, such as Streptococci, Staphylococci (generally Staphylococcus aureus) and Enterococci species. The HACEK (Haemophilus, Aggretobacter, Coxiella, Eikenella, Kingella) group of Gram negative bacteria may also cause endocarditis.
Staphylococcus aureus endocarditis is often rapidly progressive and quickly fatal without prompt antibiotic treatment. Enterococcal endocarditis typically affects elderly men and takes a subacute course. The urinary tract system may be the initial source. Streptococcus viridans are commensals of the oropharynx and can translocate and cause endocarditis, especially in the context of poor dentition and an abnormal heart valve. Streptococcus bovis is part of the gut flora, and endocarditis with this organism has been associated with colorectal cancer – warranting further investigation.

Diagnosis of infective endocarditis relies on a combination of microbiological investigation and imaging (i.e. echocardiogram). The Duke’s modified criteria is used for diagnosis and is important to know for MRCP exams (see below). To diagnose endocarditis definitively, one of the following conditions must be fulfilled:

• 2 major and 1 minor criteria
• 1 major and 3 minor criteria
• 5 minor criteria

Table 1: Duke’s modified criteria for infective endocarditis

Empiric antibiotic treatment covers the main organisms until an organism is identified, which allows targeted treatment. Generally:

• Staphylococcus aureus – high dose flucloxacillin
• Streptococci species – benzylpenicillin
• Enterococci species – amoxicillin
• HACEK organisms – ceftriaxone.
• Gentamicin can be added to some regimens for Streptococci endocarditis to shorten the duration of treatment and is often used for synergistic effects to treat Enterococci.

The indications for surgery are nuanced but essentially comprise heart failure, uncontrolled infection, large vegetations, or aortic root abscess. A vegetation of > 3c m is an indication for surgery.

Septic thrombophlebitis

Septic thrombophlebitis is seen in intravenous drug users, where injection into the vein causes a deep vein thrombosis to form, which then becomes infected. This is commonly in the groin area.
The bacteria implicated in this area may comprise usual skin flora, anaerobes and Gram negative bacteria. Ultrasound helps to confirm the presence of thrombosis with positive blood cultures proving the infection. Broad spectrum antibiotics are often required due to the infection’s polymicrobial nature, and the treatment duration is usually around 6 weeks.

Skin Infections

This topic is covered in greater detail in the Infections and Blisters topic.

Miscellaneous Infections

Bacterial infections can affect any organ – not every body system is covered in this section. First principles can be applied to approach any questions relating to this topic, and understanding the patterns of infection and presentation help guide antibiotic choice. Some key principles in microbiology include:

• Taking samples before starting antibiotics whenever possible
• Start broad spectrum antibiotic treatment – and narrow when aetiology is identified
• Control of infection source is more important than antibiotics
• Shorter durations of antibiotics are generally favoured