Infections eBook Flashcards
(110 cards)
1
Q
Infections are caused by the following groups of organisms:
A
Viruses
Bacteria
Eukaryotes – protozoa, fungi and parasitic worms
Infectious disease accounts for around 25% of deaths worldwide.
2
Q
what causes an infection
A
Organism + Host = Infection
organisms: Viruses Fungi Bacteria Protozoa
host (human): Natural defences against infection: • Physical • Lysozymes • pH • Phagocytosis • Complement & plasma proteins
3
Q
There are a number of ways that the body protects us from infection.
These include:
A
Physical defences against infections include skin barriers, mucus & cilia that capture organisms and remove them and urinary flushing. Skin diseases e.g. eczema/psoriasis can allow colonization and invasion by pathogens due to a breakdown in the physical defence barrier.
Lysozyme in tears degrades gram positive bacterial peptidoglycan.
Stomach acid protects from ingested pathogens and acid suppression increases the risk of intestinal infection.
Phagocytes – neutrophils & macrophages ingest particles including bacteria, viruses and fungi
Complement & other plasma proteins – complement cascade is activated by antigenantibody
binding or by direct interaction with bacterial cell wall components. This attracts phagocytes to the site of the infection
4
Q
local symptoms of infection
A
purulent sputum production
local erythema
presence of pus
dysuria
5
Q
Bacteria
A
Bacteria are prokaryotic cells that exist in various shapes including spheres (cocci), curves, spirals and rods (bacilli). These form the basis for primary classification.
They are also divided broadly into two main groups according to their Gram stain reaction;
Gram-positive or Gram-negative (do not retain Gram stain). Gram-positive cell walls have a thick peptidoglycan layer and a cell membrane, whereas Gram-negative cell walls have three layers: an inner and outer membrane and a thin peptidoglycan layer.
Bacteria undertake processes of growth, energy generation and reproduction independently of other cells and can grow in a wide variety of environments e.g. hot sulphur springs, freezers, low or high pH.
They are also classified as aerobic or anaerobic which relate to whether they grow in the presence or absence of oxygen.
6
Q
Antibacterials can be classified according to their site of action:
A
- Cell wall active antibacterials
beta lactams, glycopeptides, carbapenems - Protein synthesis inhibitors
aminoglycosides, macrolides, tetracyclines, clindamycin, fusidic acid, linezolid, - Nucleic acid synthesis inhibitors
quinolones, nitrofurantoin, metronidazole, trimethoprim, co-trimoxazole, rifampicin
7
Q
Antibacterial agents are also described as being either:
A
Bactericidal agents – kill the bacteria.
Bacteriostatic agents – inhibit proliferation of the bacteria but do not kill them.
8
Q
Choice of Antibacterial Agent
This depends on many factors and includes:
A
- Spectrum of activity depending on most likely pathogens as culture & sensitivities can take time.
- Local policies and guidelines.
- Resistance patterns.
- Pharmacokinetics and the ability of the antibacterial to reach site of action.
- Patient factors including renal function, hepatic function, age, co-morbidities, allergies, drug interactions, pregnancy, breastfeeding or immunosuppressed.
- Combination therapy – broad spectrum & ↓ resistance.
- Route of antibacterial agent
9
Q
Skin and Soft Tissue Infection
A
The majority of these infections are caused by Gram-positive Staphylococcus aureus and Streptococcus pyogenes. Most of these infections are due to bacteria on the skin surface penetrating the dermis or subcutaneous
tissues.
10
Q
Impetigo
A
This is a superficial skin infection usually seen in children and young adults. It is spread by direct contact. Lesions usually occur on the face and extremities and vesicular-purulent bullous or popular in appearance. Yellow or brown crusting is characteristic and secondary cellulitis can occur.
Treatment
Localised disease is treated with topical fusidic acid and mupirocin (if MRSA). More extensive disease is treated with oral antibiotics for 7-10 days (usually flucloxacillin if Staphylococcus and penicillin V for Streptococcus)
11
Q
Cellulitis
A
Cellulitis is a common cause of hospital admission in the UK and is an infection in the deeper dermis or subcutaneous fat.
Symptoms include heat, erythema, induration and localised tenderness of the skin area.
Patients often are generally unwell and with pyrexia.
It is usually caused by Streptococcus or Staphylococcus but in the immunocompromised or diabetic patients Gram-negative or anaerobic bacteria should also be suspected. There is usually evidence of an entry port in cellulitis so a careful history should be taken from the patient.
12
Q
Necrotising skin and soft tissue infections
A
This is a severe and life-threatening infection with a systemic inflammatory response, involvement of deep tissues and associated tissue destruction.
Symptoms include a combination of severe, constant pain, blistering and bruising, oedema, gas in the tissues (gas gangrene), systemic inflammatory response and multi-organ failure.
Predominately caused by aerobic gram-positive cocci (Streptococcus pyogenes and Staphylococcus aureus).
13
Q
Respiratory Tract Infections
These are divided into:
A
Upper respiratory tract infections o Common cold o Influenza o Sinusitis o Pharyngitis o Otitis media
usually self-limiting and may be caused by viruses
Lower respiratory tract infections o Pneumonia o Tuberculosis o Exacerbation of COPD o Bronchitis
14
Q
Acute otitis media (AOM)
A
AOM is an infection of the middle ear, characterized by the presence of middle ear effusion associated with the acute onset of symptoms and signs of middle ear inflammation. The most common bacterial pathogens associated with AOM are Streptococcus pneumoniae,
Haemophilus influenzae, and Moraxella catarrhalis. AOM may also be caused by virus, most commonly respiratory syncytial virus and rhinovirus.
Treatment
It is a common self-limiting disease in children and 80% of cases will resolve in 3 days without any treatment. Complications are rare and antibiotics should not be prescribed routinely to these patients.
Antibiotics may be beneficial in the following sub-groups of patients.
For example, children:
– Under two years with bilateral infection or
– With discharge from the ear or
– Who are systemically unwell (e.g. fever or vomiting) or
– With recurrent infections.
Amoxicillin or clarithromycin are the usual first line antibiotics for AOM.
15
Q
Sinusitis
A
Acute sinusitis is a common infection of the paranasal sinuses, with inflammation of the nasal and sinus mucosa. It is usually caused by viral infection but may be complicated by a secondary bacterial infection.
Symptoms of acute sinusitis include nasal discharge, nasal congestion, headache, earache, facial pain, maxillary tooth discomfort and fever.
Treatment
It is usually self-limiting so treatment with antibiotics is not necessary, unless symptoms including purulent discharge have persisted for 7-10 days, or the patient is
immunocompromised. If antibiotics are necessary amoxicillin, doxycycline or clarithromycin are
recommended first-line. Clarithromycin may be substituted for erythromycin, but this is less effective against Haemophilus influenzae, which is the cause of sinusitis in around a fifth of cases.
16
Q
Acute Bronchitis
A
In previously healthy subjects this is often viral but can be followed by infections with organisms such as Streptococcus pneumoniae and Haemophilus influenzae. This is more common in cigarette smokers or those with COPD.
Symptoms include an irritating, non-productive cough with discomfort behind the sternum. This may also be associated with tightness of the chest, wheezing and shortness of breath. The cough usually becomes productive where the sputum turns yellow or green and there is mild pyrexia.
The symptoms usually resolve spontaneously in 3-4 days in healthy patients.
Treatment
Not always necessary but may be treated with amoxicillin or a tetracycline.
17
Q
Pneumonia
A
Pneumonia is defined as an infection of the lung parenchyma (the functional tissue of the lungs). The
infection manifests itself in the alveoli, as this is the main air-exchange surface for oxygen and carbon dioxide pneumonia can be sever and life threatening. Pneumonia can be divided into two broad types:
Community Acquired and Hospital acquired.
18
Q
Community acquired pneumonia (CAP): symptoms, signs and severity – adult
A
Symptoms and signs:
Dyspnoea, cough, malaise, fever, sweats, aches and pains, pleural pain, tachypnoea, confusion
Severity:
Clinical judgement is essential in disease severity assessment, consider stability of co-morbid illness and
patient’s social circumstances.
Investigations – adult
Investigations carried out are dependent on whether patient is treated in community or hospital and on
the severity of the pneumonia. Clinical judgement is used
Severity assessment in the community – adult
The need for hospital referral should be assessed using clinical judgment and CRB-65 scoring system
19
Q
CRB65 score for mortality risk assessment in primary care
A
CRB65 score is calculated by giving 1 point for each of the following prognostic features:
confusion (abbreviated Mental Test score 8 or less, or new disorientation in person, place or time)
raised respiratory rate (30 breaths per minute or more)
low blood pressure (diastolic 60 mmHg or less, or systolic less than 90 mmHg)
age 65 years or more.
Patients are stratified for risk of death as follows:
0: low risk (less than 1% mortality risk)
1 or 2: intermediate risk (1-10% mortality risk)
3 or 4: high risk (more than 10% mortality risk).
20
Q
pneumonia General Management – adult in the community
A
Assessment of severity of pneumonia
Advise rest
Drink plenty of fluids
Stop smoking
Simple analgesia (e.g. paracetamol)
Assess for hospital referral
Pulse oximetry
Review again after 48 hours or earlier if clinically indicated include disease severity assessment
Consider hospital admission or chest radiography in those who fail to improve after 48 hours
Severity assessment – adults admitted to hospital
The CURB-65 score is used to determine the severity and subsequent management of CAP in patients
21
Q
CURB65 score for mortality risk assessment in hospital
A
CURB65 score is calculated by giving 1 point for each of the following prognostic features:
confusion (abbreviated Mental Test score 8 or less, or new disorientation in person, place or time)
raised blood urea nitrogen (over 7 mmol/litre)
raised respiratory rate (30 breaths per minute or more)
low blood pressure (diastolic 60 mmHg or less, or systolic less than 90 mmHg)
age 65 years or more.
Patients are stratified for risk of death as follows:
0 or 1: low risk (less than 3% mortality risk)
2: intermediate risk (3-15% mortality risk)
3 to 5: high risk (more than 15% mortality risk).
22
Q
pneumonia General investigations – adult patient admitted to hospital
A
Oxygen saturations / arterial blood gases in accordance with the BTS guideline for Emergency Oxygen Use in Adult Patients) Chest Radiograph U and Es to inform severity assessment CRP FBC LFTs
23
Q
pneumonia General management – hospital
A
Appropriate oxygen therapy
Assess for volume depletion – may require IV fluids
Consider prophylaxis of venous thromboembolism
Mobilisation – see BTS guidance
Nutritional support in prolonged illness
Advice and treatment regarding expectoration if sputum is present
24
Q
pneumonia Monitoring in hospital
A
Monitor - temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation,
inspired oxygen concentration (at least twice daily, consider more frequently)
If not progressing satisfactorily after 3 days of treatment – repeat CRP and chest radiograph
Review within 24 hours of planned discharge
25
pneumonia CAP – hospitalised patients
Patients admitted to hospital may need critical care management. All patients will need to have followup
arrangements made prior to discharge from hospital.
26
pneumonia Microbiological investigations – adult
These are dependent on severity of CAP, treatment in hospital or community and other factors
Microbiological tests should be performed on all patients with moderate and high severity CAP – the extent of investigation is guided by severity of CAP Diagnosis of low severity CAP - the extent of microbiological investigations should be guided by prior antibiotic therapy epidemiological factors and clinical factors (age, co-morbid illness, and severity indicators).
Examples of Microbiological investigations – adult
Sputum cultures and sensitivities (before antibiotic therapy is commenced)
Sputum Gram stain
Blood cultures (preferably before antibiotic therapy is commenced)
Urine antigen tests
PCR
Serology
Antibiotic management – adult
Consider local issues e.g. resistance patterns, C. difficile associated diarrhoea
Empirical therapy – change according to cultures and sensitivities
Switch from IV to oral antibiotic therapy appropriately.
Community Acquired Pneumonia – adult: other considerations
Complications and failure to improve
Prevention and vaccination: pneumococcal vaccination and annual influenza vaccination
Advise smoking cessation in those patients who smoke
27
Hospital acquired pneumonia (HAP)
HAP is a respiratory infection developing more than 48 hours after hospital admission. The causative organism is unlikely to be the same as those that commonly cause CAP. The choice of empirical antibiotic treatment is in accordance with the knowledge of local sensitivity and resistance patterns and individual patient’s circumstances.
Patients with hospital-acquired pneumonia should be offered antibiotic therapy as soon as possible after
diagnosis (certainly within 4 hours). A 5- to 10-day course of antibiotic therapy should be considered
28
viruses contain either
dna or rna, not both
They have a central nucleic acid core surrounded by a protein coat. Some viruses are surrounded by a lipid envelope derived from the host cell or nuclear membranes.
Viruses are intracellular parasites as they are metabolically inert. They use the host cell for synthesis of viral proteins & nucleic acid.
Many viral infections are self-limiting in immunocompetent individuals and do not require treatment other than symptomatic support.
29
Antibiotics have
no efficacy against viral infections.
30
Influenza
Influenza is an enveloped orthomyxovirus containing a negative single-stranded RNA genome divided into eight segments. The virus expresses seven proteins, three of which are responsible for RNA transcription.
31
influenza symptoms
Incubation period is 1 – 4 days, with patients being infectious for a day preceding and the first 3 days of symptoms. Headache, myalgia, fever and cough last for 3 – 4 days. A persistent dry cough can last for several weeks.
Complications include bacterial pneumonia especially in elderly and patients with cardiovascular and pulmonary disease. The severity of the illness reflects pre-existing host immunity and the causative viral strain
32
influenza Treatment
Influenza should be treated symptomatically (e.g. antipyretics, rest and fluids). If a secondary bacterial infection develops, appropriate antibiotics should be prescribed.
The neuraminidase inhibitors zanamivir (Relenza®) and oseltamivir (Tamiflu®) shorten the duration of symptoms and should be used in accordance with NICE guidelines or, in the case of pandemic, national and local guidelines.
Neuraminidase inhibitors interfere with the release of virus particles from the host cell which prevents the infection of new host cells and the spread of the respiratory disease. As replication of the influenza virus in the respiratory tract peaks between 24 and 72 hours after the onset of the illness neuraminidase inhibitors must be administered as early as possible.
33
influenza prevention
Vaccination is the first-line intervention to prevent influenza and all eligible people should receive vaccination. Vaccination provides approximately 70% protection against influenza. Due to viral mutation and short duration of protection a new vaccine needs to be produced and received annually.
Pharmacists often administer influenza vaccinations as part of an enhanced service in conjunction with local clinical commissioning groups or as part of a private PGD. More information can be found in “The Green Book”, the government guide to vaccine preventable diseases.
34
Measles and how it is transmitted
Measles is a vaccine preventable disease for which there is a national immunisation programme in the UK. It is caused by a paramyxovirus and spread by respiratory contact.
In 2011, there were 158 000 measles deaths globally, mostly children under 5 years. More than 95% of measles deaths occur in low-income countries with weak health infrastructures.
Measles vaccination resulted in a 71% drop in measles deaths between 2000 and 2011 worldwide.
It is transmitted by the aerosol route. The period of infectivity is from 4 days before until 2 days after the onset of the rash, with an incubation period of 9 to 12 days. Mortality is rare in healthy children but the mortality rate is highest in <2yrs
35
Measles symptoms
Infection begins with a 2 – 4 day cold like illness, when small white papules (Koplik’s spots) are found on the buccal mucosa. This is a diagnostic sign for measles.
A maculopapular rash then develops initially on the face then spreads rapidly to involve the rest of the body. The rash fades after a week leaving a brownish discolouration.
Secondary pneumonia, otitis media, pneumonitis, myocarditis, pericarditis and encephalitis are
complications associated with measles infection.
36
Herpes Viruses
The herpes viruses are a family of enveloped DNA viruses that characteristically cause latent infections. After primary infection the viral DNA lies dormant in various tissues and may be reactivated. They include:
Herpes simplex virus (HSV, type 1 and2)
Varicella-zoster virus (VZV)
Cytomegalovirus (CMV)
Epstein-Barr virus (EBV)
Human herpes viruses (HHV), types 6 – 8
37
Herpes simplex virus (HSV)
Reactivation may be triggered by physical factors (e.g. infection, sunlight) or psychological stress.
HSV-1 is the major cause of herpetic stomatitis, herpes labialis (cold sore), keratoconjunctivitis and encephalitis.
HSV-2 causes genital herpes (it may also be caused by HSV-1) and may also be responsible for systemic infection in the immunocompromised host.
These divisions are not rigid as e.g. HSV-2 can also cause oropharyngeal disease HSV-1 is often asymptomatic, but young children commonly develop fever, vesicular
gingivostomatitis and lymphadenopathy. Adults may exhibit pharyngitis and tonsillitis. It is highly contagious and transmitted primarily via saliva. Primary eye infection produces severe keratoconjunctivitis and recurrent infection may result in corneal scarring.
38
7 development stages of recurrent herpes labialis:
```
Phase Duration
Prodromal 1 day
Erythema 1-2 days
Papule 1-2 days
Vesicle 1-2 days
Ulcer 1-3 days
Crust 4-14 days
Skin re-epithelisation 4-14 days
```
HSV-2 infections cause painful genital ulceration that can be severe with symptoms lasting up to 3 weeks. Recurrent infections are milder and virus shedding is short-lived, but infection can be transmitted to sexual partners during this time.
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Herpes simplex virus (HSV) - Treatment
Topical, oral and intravenous antivirals are available for the treatment of HSV infections. The preparation will depend on the symptoms. Encephalitis is treated with intravenous aciclovir.
40
Varicella Zoster Virus
Varicella Zoster Virus (VZV) has only one serological type and causes the acute primary infection known as chickenpox or varicella. After primary infection the virus lays dormant in the sensory nervous system to re-emerge as shingles. It is also known as Herpes zoster.
41
Chickenpox
Chickenpox is most common in children aged 4-10. It is highly infectious and the disease is spread primarily by respiratory droplets although the vesicular fluid is also infectious.
42
Chickenpox symptoms
The first symptoms are usually a low-grade fever, malaise and sometimes mild influenza like symptoms.
A rash usually develops up to six days later. The rash commonly starts behind the ears, face or trunk and then spreads further. The spots (erythematous, maculopapular) start then turn into vesicles before becoming pustules and crusting over and healing. Vesicular fluid contains large numbers of VZV so when the vesicle ruptures, VZV is transmitted by airborne spread, direct contact with vesicle fluid or indirect contact with infected clothes, towels or bedding.
Individuals are infectious from about 48 hours before and until 5-6 days after the appearance of the first spots and the incubation period is usually 14-21 days.
43
Chickenpox Treatment
Symptomatic management is all that is usually required in immunocompetent individuals and otherwise healthy children between the ages of 1 month and 12 years.
Antipyretics for fever and flu-like symptoms.
Oral antihistamines and topical preparations (e.g. crotamiton, calamine) can be used for itching.
For immunocompetent adults and adolescents (aged 14 years or older), aciclovir is considered if they present within 24 hours of rash onset, particularly for people with severe chickenpox or those at risk of complications, such as smokers or people using corticosteroids. Normally oral treatment will suffice at a dose of 800mg five times daily for seven days.
Immunocompromised individuals will normally require intravenous therapy at a dose of 10mg/kg TDS for five days.
If serious complications (such as pneumonia, encephalitis, or dehydration) are suspected, admit to hospital for parenteral antiviral treatment.
44
Shingles
Shingles results from reactivation of latent VZV. Virus reactivation may be caused by age, disease, physical or emotional stress, fatigue or in the immunocompromised.
45
Shingles Symptoms
The onset of a rash in shingles is usually preceded by severe nerve pain. Tingling, itching or burning may occur over the affected dermatome.
The rash is almost always unilateral & localised. Most common sites include abdomen, chest, face & neck.
Lesions start as erythematous and maculopapular, developing into vesicles and eventually crusting over. Transmission is by direct contact so the affected area should be kept covered.
Nerve pain is the most troublesome complaint.
46
Shingles treatment
In adults oral antivirals (aciclovir, famciclovir or valaciclovir) should be used to prevent the
complication of post-herpetic neuralgia. Antivirals should be started within 72 hours of the onset of the rash. Antivirals reduce complications and reduce viral shedding.
Complications of shingles include post herpetic neuralgia which can be a steady burning, aching pain, a jabbing pain or a combination. This can continue for weeks (sometimes years) and is 26 more likely in patients aged >80yrs. Treatments recommended for post-herpetic neuralgia include capsaicin cream, and adjunctive neuropathic pain relief with agents such as amitriptyline (low dose), gabapentin and sodium valproate.
47
Superficial Fungal Infections
Superficial fungal infections commonly affect the skin, hair and nails. They are usually caused by the fungi shown in table 2.
Fungi
Type of fungus
Main infections
```
Candida albicans
Yeast
-Oral thrush, vaginitis, cutaneous
candidiasis
onychomycosis
```
```
Epidermophyton
Microsporum
Trichophyton
-Dermatophytes Tinea (ringworm) of skin & hair
-Onychomycosis
```
Malassezia furfur Dimorphic
Pityriasis versicolor
The genus Candida contains a number of species, including C. albicans which is the most frequently isolated pathogen. C. albicans is a commensal of the mouth and gastrointestinal tract although any organ in the body can be invaded by Candida. It is the most common cause
of opportunistic fungal infections worldwide.
48
Superficial Fungal Infections Symptoms
Candida spp. cause pain and itching with creamy white curd-like plaques on mucosal surfaces such as the tongue, oropharynx, oesophagus and vagina. Oral thrush is seen particularly in the very young, in the elderly, diabetics, following antibiotic therapy and in those who are immunosuppressed. It is also a common side-effect from the incorrect use of corticosteroid inhalers for respiratory diseases. Poor inhaler technique leads to the local deposition of corticosteroids (an immunosuppressant) on the mouth and palette, increasing the likelihood of Candida overgrowth. Systemic invasion is common in neutropenic patients.
49
Oral thrush Treatment
Candidal infections can be treated with topical imidazoles (e.g. clotrimazole, econazole, and miconazole), topical terbinafine or nystatin. The choice of agent is dependent on the location and severity of the infection. For instance nystatin is only used to treat oral and oesophageal
candidiasis.
If the symptoms are not responsive to topical therapy a systemically active azole such as fluconazole or itraconazole should be used.
50
Onychomycosis (fungal nail infection)
Onychomycosis is the invasion of the nail plate by a fungus. This is a common condition with an estimated prevalence of 3-8%. It affects males more commonly than females and prevalence increases with age. It is considered to be a cosmetic condition but if left untreated can lead to pain and discomfort and may also spread to surrounding tissues. It is most commonly caused by dermatophytes but can be caused by Candida spp.
51
Onychomycosis (fungal nail infection) Treatment
Amorolfine, tioconazole and undecanoate-containing nail lacquers, paints and creams can be used for topical therapy if no more than two nails are affected. Systemically active drugs e.g. terbinafine, itraconazole are used for more advanced infection.
52
Tinea (ringworm)
```
Dermatophyte infections may present as red scaly patch-like lesions which spread outwards leaving a pale, healed centre (ringworm). The lesions are itchy but rarely painful. If present on the scalp it can be associated with hair loss and scarring. Diagnostic labels are based on the site of infection:
Tinea capitis (head & scalp)
Tinea corporis (trunk lesion)
Tinea pedis (athlete’s foot)
```
53
Tinea (ringworm) treatment
Topical imidazole antifungal such as clotrimazole or
miconazole or a shampoo containing ketoconazole can
be used depending on area affected.
54
Pityriasis versicolor
Pityriasis versicolor is caused by Malassezia furfur which infects the stratum corneum, causing brown, scaly macules with depigmentation.
55
Pityriasis versicolor Treatment
Topical imidazoles such as ketoconazole shampoo. If topical treatment fails a systemic azole e.g. fluconazole can be used.
56
Systemic fungal infections (deep mycoses)
Due to an aging population, increasing numbers of organ transplants and a greater number of immunosuppressive therapies the number of invasive fungal infections is increasing. Systemic fungal infections are usually opportunistic infections occurring in immunocompromised
patients.
57
Candida infections
Systemic invasion is more common in neutropenic patients. Neutrophils, monocytes and macrophages are important defense mechanisms against fungal disease so impairment to the functioning of these cells can reduce the ability of the immune system to clear fungal pathogens.
Candida spp. can also cause systemic and line-associated infection following broad-spectrum antimicrobial therapy in intensive-care patients.
Candidaemia (Candida in the blood) may result in abscesses or infection in various organs (e.g. brain, liver, eye, kidneys and gastrointestinal tract) and endocarditis.
58
Aspergillus infections
Systemic aspergillus infections usually only occur in the immunocompromised host although they can also cause infection in immunocompetent people that have had recent tissue damage.
The four organisms regularly associated with human infections are:
Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, Aspergillus terreus
Aspergillomas are formed when Aspergillus grows in a clump or ball in a lung cavity, or invades previously healthy tissue, causing an abscess. Most patients have a persistent productive cough, weight loss, haemoptysis, wheeze and finger clubbing.
Invasive aspergillosis mainly affects immunocompromised patients and may progress quickly or have a more indolent, chronic course e.g. in AIDS patients. Symptoms include dry cough, fever, pleuritic chest pain and dyspnoea.
59
Cryptococcosis infections
Optimum conditions for growth of the yeast
Cryptococcus neoformans is soil mixed with bird excreta. People who are exposed to dirt containing bird droppings, such as poultry farm workers, and groundkeepers of parks, are at risk of inhaling the yeast.
Cryptococcosis can cause pneumonia and cutaneous infections, but more seriously and more common in immunocompromised patients, cryptococcal meningitis.
60
Pneumocyctis jiroveci (previously pneumocystis carinii) infections
This was previously thought to be a protozoan but is now known to be a fungus. Pneumocyctis jiroveci causes pneumonia in the immunocompromised (severe T-cell dysfunction), especially those with a CD4 count <200 e.g. AIDS. Before the HIV epidemic this infection was rare.
Symptoms include dyspnoea which develops insidiously over days or weeks, unproductive dry cough and fever. Fine basal crackles may be heard on clinical examination.
Treatment is with high dose oral co-trimoxazole or intravenous pentamidine. Prophylactic treatment with oral co-trimoxazole is usually given to patients who are likely to be at risk e.g. haematological cancers, HIV patients.
61
Treatment of Systemic fungal infections
The selection of antifungals available to treat invasive fungal infections has expanded since the turn of the century. Selection is based on indication, site of infection, patient comorbidities and local guidelines. This is because it is both difficult and time consuming to culture fungi and often cultures may grow commensal flora rather than the pathogenic species.
62
Azoles
Imidazole & triazole
derivatives
Mode of action Main uses
Target ergosterol by inhibiting the fungal cytochrome P450 enzyme 14-alphademethylase, preventing the conversion of lanosterol to ergosterol causing inhibition
of fungal growth and replication
Superficial and systemic infections.
Varies depending on agent,
63
Polyenes
Amphotericin B
Nystatin – topical only
Mode of action, Main uses
Interacts with ergosterol in the cell membrane, which causes an increase in membrane permeability and leakage of cellular components.
Broad spectrum antifungal agents
64
Allylamines
terbinafine
Mode of action, Main uses
Inhibits squalene epoxidase, an essential enzyme in the ergosterol biosynthesis pathway, which leads to a deficiency of ergosterol in the fungal cell membrane. This leads to destruction of the cell.
Dermatophyte infections of the nail Tinea infections
65
```
Echinocandins
Casopfungin
Anidulafungin
micafungin
Mode of action, Main uses
```
Inhibits the synthesis of β (1,3)-glucan synthase an essential component of the cell wall of many filamentous fungi. They are generally fungicidal against candida spp
but fungistatic against aspergillosis spp
Invasive aspergillosis Invasive candida
66
Flucytosine
| Mode of action, Main uses
Competitive inhibitor of uracil metabolism. Converted to 5-fluorouracil in susceptible fungal cells and incorporated into fungal. RNA to exert its effect.
Cryptococcal meningitis in combination with amphotericin
67
Griseofulvin
| Mode of action, Main uses
Unknown
? inhibits fungal mitosis
Dermatophyte infection of skin, hair & nails
68
Nystatin is
Nystatin is too toxic for systemic use and is not orally absorbed so it is used only topically, mainly for oral or oeophageal thrush.
69
Amphotericin is
Amphotericin is used for suspected fungal infections in immunocompromised patients. It has an affinity for the cholesterol found in mammalian cells so is quite toxic. Toxicity is reduced by putting it into a lipid formulation.
70
Griseofulvin is
Griseofulvin is well absorbed orally and is incorporated into the stratum corneum of the nail so was used to treat fungal nail infections although its use has been superseded now by terbinafine. Griseofulvin is quite toxic and teratogenic and fetotoxic. Women should avoid
pregnancy during & for 1 month after treatment; men should avoid fathering children during treatment and for 6 months after. Treatment must be continued until uninfected tissue grows.
71
Terbinafine is
Terbinafine is well tolerated apart from some GI disturbances. It is indicated in superficial dermatophyte infections which have failed to respond to local therapy.
72
Azoles include:
Imidazole antifungals including ketoconazole and miconazole.
Triazole antifungals including fluconazole, itraconazole, posaconazole and voriconazole
Triazole azoles can be used to treat superficial & systemic candida infections. They are well absorbed orally. Fluconazole is useful for the prophylaxis of fungal infections in neutropenic patients. Fluconazole and voriconazole penetrate the Blood-brain barrier well but some azoles have many interactions.
Voriconazole – invasive aspergillosis and invasive fluconazole resistant Candida spp.
Flucytosine is given in combination with amphotericin as fungi develop resistance quickly, is converted to 5-flurouracil (a cytotoxic agent) to exert its effect. SE’s include bone-marrow suppression, thrombocytopenia & abnormal liver function tests.
Echinocandins – caspofungin is a newer agent indicated for invasive aspergillosis and candidiasis in patients who are unresponsive or intolerant to amphotericin or itraconazole.
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Healthcare Associated Infections
These are infections acquired whilst in hospital or as a result of a healthcare intervention. They develop at least 48 hours after a patient is admitted to hospital or up to 48 hours after discharge from hospital. Reducing these infections is a key focus for the Department of Health.
Hospital acquired infections require longer durations of treatment, more potent (and usually toxic) antibiotic regimens and have a poorer prognosis than community acquired infections.
This is because hospitals are a breeding ground for exotic and resistant bacteria.
Examples of these infections include:
o Meticillin-resistant Staphylococcus aureus - MRSA
o Clostridium Difficile – C.diff
o Extended spectrum beta lactamases - ESBL
o Hospital acquired Pneumonia – HAP
o Carbapenemase producing Enterobacteriaceae
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MRSA
MRSA was first identified in 1960’s & became a major problem in 1990’s. It evolved to develop a penicillin-binding protein that continues to function in the presence of beta-lactam antibiotics. Many people carry MRSA as part of the commensal flora of the nasal tract.
Risk factors for acquiring MRSA include:
Prolonged or recurrent hospital stays
Invasive medical devices
Treatment with some antibiotics especially cephalosporins, quinolones and macrolides
Elderly patients
Immunocompromised
Diabetes
Previous colonisation or infection with MRSA
Sites commonly infected include nose, groin, broken skin, pressure sores, wounds, stoma sites, entry of invasive devices, sputum if intubated.
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Treatment of MRSA
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Glycopeptides have been the main treatment for MRSA for many years but there are several new agents with activity against MRSA now available.
Oral agents active against MRSA include:
Doxycycline
Trimethoprim
Fusidic acid
Rifampicin
Linezolid
Clindamycin
Intravenous agents include
Vancomycin
Teicoplanin
Linezolid
Tigecycline
Daptomycin
Decolonisation regimens for MRSA include mupirocin nasal ointment and chlorhexidine or triclosan topical wash for the skin. Most of the deaths involving MRSA were in the older age groups. Newer antibiotics and improved infection control policies and antimicrobial
stewardship have resulted in the drastic reduction in the number of MRSA bacteraemia cases reported and the number of deaths from MRSA infection.
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Clinical features c diff
This can cause mild diarrhoea through to the potentially fatal complications of pseudomembranous colitis and toxic megacolon.
Usually patients present with more than three, loose or unformed stools per day, abdominal pain with a history of previous antibiotic exposure. Clostridium difficile has a potent smell that experienced healthcare professionals can identify. Main causative antibiotics include fluoroquinolones and third-generation cephalosporins, although any broad spectrum antibiotic can be responsible.
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c diff treatment
Treatment with oral metronidazole or oral vancomycin for 10-14 days. More recently fidaxomicin has been licensed for treatment, it is often (but not always) reserved for resistant cases
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Antimicrobial resistance
Resistance to antibiotics is a major public health threat and inappropriate use of these agents drives the development of antimicrobial resistance. Infections then become more difficult to treat which increases the morbidity, duration and cost of the illness.
Examples of inappropriate use of antibiotics which may encourage resistance:
Antibacterial agents for non-bacterial infections (e.g. viral)
Longer or shorter duration of treatment than necessary
Using broad spectrum antibiotics unnecessarily
Combination of antimicrobials with the same spectrum of activity
Single agent use when should be used in combination to reduce risk of resistance e.g. fusidic acid, rifampicin
Incorrect doses of antimicrobial, i.e. too low
Inappropriate route
Most antibiotic use is in two areas: in humans in the community, and in animals for growth promotion and prophylaxis (see table 9). The data in the table suggest that a high proportion of antibiotic use is of questionable therapeutic value. Resistance is driven by antibiotic use in
human and agricultural/veterinary practice.
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Mechanisms of antibiotic Resistance
Clinical resistance, i.e. whether the antibiotic will or will not work in a patient or animal, is a more complex concept in which many other factors are involved such as the precise location of the infection, the distribution of the drug in body fluids and the state of the patient's immune system.
Microorganisms can exhibit resistance to antimicrobials in a variety of mechanisms.
They may have inherent resistance (intrinsic resistance) to the antimicrobial or develop
resistance via genetic elements (acquired resistance).
These resistant microorganisms can share their DNS with other bacteria by
Conjugation (plasmid transfer between cells)
Transduction (DNA transfer by a bacteriophage)
Transformation (uptake of DNA when cells break down)
Methods of acquired resistance to antimicrobials include:
Enzymes inactivate the antibacterial before it binds to the bacterium e.g. beta lactamases inactivating penicillins
Antibacterial is less able to permeate the bacterial cell wall e.g. aminoglycosides inactive against anaerobic bacteria as enter via oxygen-dependent transport mechanism.
Antibacterial is actively removed from the bacterial cell e.g. tetracyclines & E.coli
Mutation at the site where the antibacterial binds to the bacterium e.g. rifampicin & alteration of RNA polymerase gene
Bacteria develop new synthesis pathways e.g. trimethoprim resistance
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The Growing Problem of Antimicrobial Resistance
You have probably heard of MRSA and think that this is the biggest threat posed from resistant microbes, however currently there are a number of treatment options for MRSA. Of much more concern is the growing problem of resistant Gram negative bacteria. Klebsiella
penumoniae is responsible for urinary tract, respiratory tract and bloodstream infections.
Combined resistance to fluoroquinolones, third-generation cephalosporins and aminoglycosides rose from 15 to 21% in the EU between 2010 and 2013, this leaves carbapenemases as the last effective group of antibiotics against these bacteria and as you can see from the maps below, resistance to these antibiotics is being reported in the EU.
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Political Responses to Antimicrobial Resistance
The House of Lords review on antibiotic resistance in 1998 highlighted areas where resistance were threatening to occur next and made three main recommendations:
1. Ensuring there is widespread recognition that antibacterial resistance is a major threat to public health.
2. There should be an increase in emphasis in the continuing professional development of prescribers in the area of antibiotic prescribing.
3. The Government and health authorities must do more to educate the public about the proper use of antimicrobials, in particular targeting mothers of young children.
This work was supplemented in 2003 by a £12m funding programme from the Department of Health: the Hospital Pharmacy Initiative (HPI). This promoted prudent use of antibiotics over a three year period through enhanced clinical pharmacy activity in hospitals. The key learning
points were:
1. To facilitate the development of clinical pharmacy services and provide a focus on antibiotic management
2. Focus on key areas such as antibiotic use in surgical prophylaxis, antibiotic use in children and infection control
3. Ensure hospital antibiotic policies are in line with current best practice and are evidence based
After something of a nadir the debate surrounding antimicrobial resistance was reignited following comments from the Chief Medical Officer, Dame Sally Davies in 2011. The document
“Start SMART the focus” provides a framework for antimicrobial prescribing in hospitals to deal
with and reduce resistance rates. This was followed by the UK Five Year Antimicrobial Resistance Strategy 2013-2018, this focusses activities around three strategic aims.
1. Improving the knowledge and understanding of antimicrobial resistance
2. Conservation and stewardship of the effectiveness of existing treatments
3. Stimulating the development of new antibiotics, diagnostics and novel therapies
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Reducing the impact of resistance
In November 2013 the Antimicrobial Resistance and Healthcare Associated Infection (ARHAI)
committee, published a document entitled Antimicrobial prescribing and stewardship competencies. This describes the knowledge, skills and behaviours that independent prescribers must demonstrate in order to support effective antimicrobial stewardship. This can form a useful tool for pharmacists when assessing the clinical appropriateness of prescriptions.
Community
Approximately 80% of human use of antibiotics occurs in the community, mainly for respiratory tract infections. The DoH Standing Medical Advisory Committee report “The Path of Least Resistance” in 1998 had the following key messages to reduce inappropriate prescribing:
Do not prescribe antibiotics for self-limiting conditions e.g. simple coughs and colds
Do not prescribe antibiotics for viral sore throats
Limit prescribing for uncomplicated cystitis to 3 days in otherwise fit women
Limit prescribing of antibiotics over the telephone to exceptional cases
The TARGET antibiotics toolkit, (Treat Antibiotics Responsibly: Guidance and Education Tools) provides some useful resources for educating patients on
antimicrobial resistance.
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Hospital
| Start SMART the focus recommends the following key messages:
Antibacterials should be prescribed with as narrow a spectrum of activity as possible
Actively review antibiotic prescriptions 48 hours after the initial prescription
As short a course as possible should be prescribed
Antibacterials should be switched from i/v to oral as soon as possible
Reducing routine use of antibiotics for surgical prophylaxis to a minimum
Antibiotics should not be started immediately in all suspected infections. Certain patients need immediate treatment e.g. febrile neutropenia or septicaemia but many cases antibiotics can be withheld until clear evidence of infection or culture results
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Sepsis
Sepsis is defined as a life threatening organ dysfunction caused by a dysregulated host response to infection. It is a leading cause of avoidable death with 123,000 cases and 37,000 deaths per year, more deaths than breast, bowel and prostate cancer combined.
Sepsis has been recognised for many years but it was not clinically defined until the late 1990s. The majority of deaths occur in frail elderly patients who are less able to withstand serious infections, however there continue to be reports of tragic deaths in children and relatively fit young adults where the signs of sepsis were not recognised and treated early enough.
As a result of some high profile death a NHS action plan was set up in 2015 to drive up the quality of
care for patients with sepsis across the country. This involved targeted educational programmes for all
professions and grades of staff within the NHS to ask the question: Could this be sepsis? A second sepsis action plan was published in 2017.
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What is sepsis?
Sepsis occurs when a patient’s organs start to fail following an infection, this may happen as a result of
the infection itself, or more frequently as a result of a complex process where the host’s immune system
causes oedema, hypercoagulation and tissue breakdown.
The easiest way to understand the dysregulated host response to an infection in sepsis is to introduce
you to an organ you will have heard of previously but may never have thought of as an organ: the endothelium.
The endothelium is the layer of epithelial cells which lines the lumen of all blood vessels and lymphatics.
It covers an area of approximately 1000m2 in adults and regulates vasomotor tone, the movement of cells and nutrients in and out of tissues (in the capillaries) the coagulation system and the balance of inflammatory and anti-inflammatory signalling.
In sepsis the endothelium starts to breakdown leading to increased leucocyte adhesion, vasodilation, a shift to a procoagulant state and a loss of barrier function all of which lead to widespread tissue oedema. Endothelial changes alter permeability in other organs which lead to failure
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Organ Pathophysiology Sequelae
Lung
- Increased capillary permeability – causes protein rich fluid to accumlate
- Increased oedema floods alveoli, gas exchange impaired
Gastrointestinal tract
- Gut epithelium becomes more permeable, activated pancreatic enzymes cause autodigestion of GIT
- Pathogenic bacteria may translocate through epithelium, and cause secondary opportunistic infections
Liver
- Impaired clearance of bilirubin
- Jaundice and cholestasis
Brain
- Endothelial dysfunction disrupts Blood Brain Barrier
- Increased disposal to delirium and encephalopathy as nitrogen containing compounds enter CNS.
Immune system
- Depletion of CD4 and CD8 T cells due to apoptosis
- Reduced response to secondary infection
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Clinical Signs of Sepsis
Early-onset organ dysfunction may be demonstrated in a number of ways but by far the most effective way is by regular monitoring of a patient’s vital signs. Patients with sepsis may not always present with the classical symptom of systemic infection, a raised temperature, however one of the most common features is hypotension caused by a reduction in vascular resistance mediated by the endothelium
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NEWS score
Respiratory rate
- 12-20
- Increased >25
Oxygen saturation
- 94-98%
- <94
Heart rate
- 60-100
- Increased above 130
Temperature
- 36.1-38.0
- Increased or decreased
Systolic Blood Pressure
- 100-200
- Decreased
Level of consciousness
- Alert
- Altered/impaired
Vital signs measured in the national early warning score (NEWS)
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There are a number of scoring systems which can be used to identify patients with sepsis
There are a number of scoring systems which can be used to identify patients with sepsis including the NEWS (National Early Warning Score), qSOFA (quick SOFA) and SOFA (Sequential Organ Failure Assessment. NICE have also recently developed risk stratification tools to identify patients at risk of severe illness or death from sepsis, these are available in NICE NG51.
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If sepsis is suspected in any patient
If sepsis is suspected in any patient they should be transferred to hospital as quickly as possible (if they
are not already there). They should be immediately reviewed by a senior clinical decision maker and
blood tests should be undertaken for the following:
Blood gases including glucose and lactate levels
Blood cultures
FBC
CRP
U and Es
Clotting Screen
If the location of the infection is known samples should be sent for culture and sensitivities as per normal for an infection
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Treatment sepsis
It is vital to give a broad spectrum antibiotic at the maximum recommended dose within an hour of sepsis being diagnosed or any high-risk criteria being identified via a scoring system.
Further treatment recommendations are based on patient factors (see NICE NG51 for further detail).
These involve fluid resuscitation and the use of vasopressors such as noradrenaline to maintain
adequate blood pressure.
Hypotension is associated with a reduction in tissue perfusion and thus further organ damage. Elevated
serum lactate levels have been associated with a poor prognosis (increased risk of death). The recommendations for patients with abnormalities in these two parameters is summarised in the table below:
Lactate > 4mmol/litre OR
SBP < 90mmHg
500ml i/v crystalloid fluid as bolus over 15
minutes
Refer to critical care for central venous access
and assessment for vasopressor therapy.
Lactate > 2mmol/litre 500ml i/v crystalloid fluid as bolus over 15 minutes
Lactate <2mmol/litre Consider giving i/v fluid bolus
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All patients with high risk criteria should be monitored
All patients with high risk criteria should be monitored at least every 30 minutes. Failure to respond to initial antibiotic treatment and fluid resuscitation would be defined as:
SBP persistently below 90mmHg
Reduced level of consciousness
Respiratory rate >25 breaths per minute
Lactate not reduced by more than 20% of the initial value within one hour.
Failure to respond to treatment would certainly indicate the need for High-dependency care.
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what kind of disease is sepsis
Sepsis is a heterogeneous disease which may affect patients in a number of different ways, a number of
specific treatments have been trialed in recent years without success. The cornerstone of treatment which has improved prognosis in the last 20 years remains prompt antibiotic treatment and fluid resuscitation if necessary.
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Cellulitis treatment
High dose i/v flucloxacillin (unless penicillin allergic, in which case use clarithromycin). If Streptococcal infection is confirmed with culture and sensitivity testing, penicillin V or G should substitute flucloxacillin. If a gram negative or anaerobic infection is suspected then broad spectrum antibacterials such as co-amoxiclav should be used.
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Fungal Infections
Fungi are eukaryotic organisms; they are distinct from plants in not containing chlorophyll. They can be macroscopic (mushrooms) or microscopic (moulds and yeasts). Only a few species of fungi actually cause human disease (there are more than 200,000 species) and systemic fungal infections are generally uncommon although the incidence has increased in the past 20-30 years. Fungal infections are transmitted by inhalation of spores or by contact with the skin.
Fungal spores can lie dormant for long periods of time until conditions are right for growth.
Fungal infections in humans are known as mycoses.
Fungi are grouped into three major categories:
Yeasts which are single cells, rounded organisms that multiply by budding or fusion.
Moulds which are long tubular filaments (hyphae) which grow by branching and longitudinal extension of hyphae.
Dimorphic fungi can exist as either yeast or mould dependent on environmental factors such as temperature.
The principle sterol in many fungal species is ergosterol which differs to mammalian cells where the principle sterol is cholesterol. This is a major target for antifungal drugs.
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Clostridium difficile
Clostridium difficile is part of the normal gut flora and is a spore-bearing Gram-positive bacterium. It produces enterotoxins A and B which cause fluid secretion and tissue damage.
Some hyper virulent strains e.g. type 027 are associated with more severe disease. Bacterial spores can contaminate hospital wards and spread the infection rapidly between patients.
Risk factors include:
– > 65years
– Treatment with antibiotics
– Proximity to infected patients
– PPI use
– Surgery
– Chemotherapy
Hand washing with soap and water is paramount in reducing healthcare associated infections, alcohol gels are effective against non-spore producing organisms but do not kill C.difficile spores or remove them from hands. Spores can survive for months or years.
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Table 3 Risk factors for invasive fungal disease
Risk Factors for invasive fungal disease Examples
Immunosuppression Organ or bone marrow transplant
HIV/AIDS
Systemic corticosteroids Autoimmune conditions e.g. rheumatoid arthritis
Malignancy Solid or haematological malignancies
Severe debilitation Intensive care patients, burns, severe
trauma
Use of broad spectrum antibiotics Repeated courses of penicillins, cephalosporins or quinolones
Invasive devices IV catheters and devices
Extremes of age Neonates & elderly more susceptible
Endocrine disorders Diabetes mellitus
Systemic fungal infections are difficult to treat and can be life threatening. Diagnosis of a systemic fungal infection in these patients can be difficult because symptoms may be minimal and are often non-specific. They should be always be considered in immunocompromised patients with symptoms of infection not responding to broad-spectrum antibiotics.
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First line antibiotic treatment for acute sinusitis in adults over 18
First choice: Phenoxymethylpenicillin - 500 mg four times a day for 5 days
First choice if systemically very unwell, symptoms and signs of a more serious illness or condition, or at high risk of complications: Co-amoxiclav - 500/125 mg three times a day for 5 days
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types of influenza
There are three types, A, B and C, determined by nucleoprotein. Type A infects humans and animals whereas types B and C infect humans only. Influenza A is the cause of world-wide pandemics.
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What does the lipid bilayer of influenza contain
The lipid bilayer contains two glycoproteins haemagglutinin (H) and neuraminidase (N) proteins
that interact with host cells. The virus type is based on these H & N antigens.
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Annual epidemics of influenza occur..
Annual epidemics of influenza occur due to minor antigenic changes (antigenic drift) in H and N.
Pandemics occur every 10-40 years due to major antigenic shifts of an influenza virus. The
antigenic shifts result in severe outbreaks due to an absence of any partial pre-existing
immunity in the human population to the completely new influenza strain. These strains are
usually traced back to infected birds, poultry or pigs.
Eg swine flu
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In 2017/18 the following groups are eligible for flu vaccination:
all children aged two to eight (but not nine years or older) on 31 August 2017 (with LAIV)
all primary school-aged children in former primary school pilot areas (with LAIV)
those aged six months to under 65 years in clinical risk groups
pregnant women
those aged 65 years and over
those in long stay residential care homes or other institutions such as prisons
• carers
Frontline health and social care workers should be provided flu vaccination by their employer. This includes general practice staff.
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Pilot projects for influenza vaccination in August 2014
Pilot projects were set up in August 2014 to introduce administration of the annual influenza
vaccine to all children from 2-16 years of age. The success of these projects in reducing the
burden of flu amongst local populations (herd immunity) has led to their establishment
nationwide.
Children receive the live attenuated influenza vaccine (LAIV) currently licensed as Fluenz tetra®.
Two advantages of this vaccine are that it is delivered via an intranasal route rather than the
usual intramuscular route. This allows for a virtually pain-free vaccination process, which does
not have to be supervised by a healthcare professional with injection training. The second
advantage is that the vaccine is tetravalent (it contains two strains of Influenza A and two of
Influenza B), influenza B tends to affect children more than adults thus this vaccine is more
effective than the usual one which contains only one strain of influenza B
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Examples of yeast
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C albicans
C tropicalis
C parapsilosis
C krusei
C glabrata
Cryptococcus
neoformans
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Examples of moulds
Aspergillus spp
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Examples of dimorphic fungi
Coccidioides spp,
Histoplasma spp
Blastomyces
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C krusei not effective against
fluconazole
108
Cryptococcus
| neoformans not effective against
Anidulafungin
Micafungin
Caspofungin
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Aspergillus spp not effective against
fluconazole
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Coccidioides spp,
Histoplasma spp
Blastomyces not effective against
Flucytosine
