Advanced Infections eBook

Question 1

Vaccine Preventable Diseases

Answer 1

diphtheria
tetanus
pertussis (whooping cough)
pneumococcal disease (certain serotypes)
human papillomavirus (certain serotypes)
Haemophilus influenzae type b (Hib)
Polio meningococcal disease (certain serogroups)
Measles
Mumps
Rubella
Rotavirus
Influenza
Shingles

Question 2

Antimicrobials requiring therapeutic drug monitoring

Answer 2

Gentamicin
Vancomycin
Teicoplanin
Amikacin
Tobramycin
Chloramphenicol (I/v use)

Question 3

Gentamicin

Answer 3

Gentamicin is to most commonly monitored drugs in hospital pharmacy practice in the UK. It is an extremely useful drug when used correctly having a good spectrum of activity against gram negative bacteria often responsible for urosepsis.
Gentamicin is exclusively excreted by the kidneys and is highly hyrdrophillic meaning it is not distributed into fatty tissue, both these factors have consequences for dosing

Question 4

Gentamicin - Side effects

Answer 4

Damage to the cochlear and vestibular apparatus
- loss of balance, tinnitus, loss of hearing.

May cause renal damage - risk of nephrotoxicity is increased with prolonged treatment.

• Concurrent use of other nephrotoxic drugs may exacerbate renal damage.
• Use with ototoxic diuretics, e.g. furosemide, may increase risk of ototoxicity and nephrotoxicity.

May cause allergic reactions, nausea, vomiting and rashes.

Question 5

Gentamicin - Cautions and CI

Answer 5

Gentamicin is contra-indicated in severe renal impairment and pregnancy.

Question 6

Hartford regimen

Answer 6

Based on a consistent dose of 7mg/kg gentamicin calculated from the lower value of the ideal body weight or actual body weight. The plasma concentration is measured 6-14 hours after first dose to determine dosage interval. The Hartford Nomogram is used to determine whether patient should receive gentamicin every 24 hours, 36 hours or 48 hours

Question 7

Tuberculosis (TB)

Answer 7

Tuberculosis (TB) is an infectious disease caused by the bacteria Mycobacterium tuberculosis, and occasionally M. bovis or M. africanum

Question 8

Risk factors associated with TB

Answer 8

 Social deprivation – overcrowding e.g. prisons, poverty, homelessness, poor nutritional intake, smoking, drug & alcohol misuse
 HIV
 Diabetes
 Malignancy
 TNF antagonist therapy
 Immigration e.g. cities, from high incidence area
 Close contacts of TB cases
 Living in high incidence area

Question 9

Symptoms - TB

Answer 9

It can affect any organ of the body and mimics both inflammatory and malignant diseases.
In many patients primary tuberculosis in the early stages is symptomless.
Pulmonary disease may present with a chronic cough, haemoptysis, shortness of breath, fever & weight loss. Tissue destruction can result in scarring & fibrosis and if the infection is left untreated erosion through blood vessels can lead to massive haemoptysis.
Tuberculosis meningitis presents with fever, headache, neck stiffness and slowly deteriorating level of consciousness. Children with TB can be asymptomatic and there is a higher incidence of extra pulmonary TB e.g. CNS. Miliary TB is where minute tubercles form in different organs due to the dissemination of bacilli through the body by the blood stream and is more common in infants & young children.
In advanced HIV disease extra-pulmonary TB is common & can affect liver, spleen, pancreas, bone marrow

Question 10

Diagnosis of TB

Answer 10

Pulmonary disease requires:

 Three sputum samples for microscopy and culture (may need to induce sputum or broncheoalveolar lavage). Sputum and tissue samples are examined for the presence of acid-fast bacilli (AFB).
 Other specimens will depend on the site of infection of TB.
 Chest X-ray.

Question 11

Treatment - TB

Answer 11

There are two phases of TB treatment:
 Initial phase – rifampicin, isoniazid, pyrazinamide & ethambutol for 2 months.
Aim to eradicate actively growing & semi-dormant bacilli.
 Continuation phase – rifampicin & isoniazid for a further 4 months to eliminate residual bacilli & reduce the risk of treatment failure or relapse.

Question 12

Pulmonary tuberculosis is usually no longer infectious after

Answer 12

2 weeks appropriate treatment with anti-TB agents.

Question 13

Drug Resistant Tuberculosis

Answer 13

No new anti-TB agents have been discovered in the last 30 years and resistance to one or more drugs has become problematic, especially with patients born outside of the UK. This can be either acquired or primary resistance.
Second line drugs are available for the treatment of TB but have more side effects, are more invasive and less well tolerated than the standard treatments. Treatment is also significantly more expensive than first line agents. Resistance to second line agents is also starting to
become a problem.
Drug-resistant TB exists when a treatment suppresses the growth of susceptible bacilli but allows multiplication of resistant organisms. Isoniazid resistance was diagnosed in approximately 6% of reported cases of TB in the UK in 2017
Multi-drug resistant TB (MDR-TB) is resistant to both isoniazid and rifampicin this accounts for approximately 1.6% of cases in the UK in 2017. Extensively-drug resistant tuberculosis (XDR TB) is defined as tuberculosis resistant to any fluoroquinolone and at least one of three
injectable second-line drugs (capreomycin, kanamycin and amikacin), in addition to multidrug resistance.

Question 14

Risk factors for MDR-TB in UK

Answer 14

 Prior TB treatment, prior TB treatment failure
 Patients from countries with high MDR-TB prevalence
 Residence in London
 Age - highest rates between 25-44
 Male gender
 HIV-positive patients
 History of exposure of MDR-TB

Question 15

Side effects of tuberculosis treatment

Answer 15

• GI symptoms
• Non-gouty polyarthritis - pyrazinamide
• Rash – rifampicin
• Urine and bodily fluid discolouration - rifampicin
• Drug fever – temperature > 39°C & patient well
• Hepatotoxicity
• Peripheral neuropathy - isoniazid
• Flu-like symptoms - rifampicin
• Optic neuritis – ethambutol

Question 16

Pyridoxine (Vitamin B6)

Answer 16

Pyridoxine (Vitamin B6) can be given prophylactically to patients with diabetes, alcohol dependence, chronic kidney disease, pregnancy, malnutrition, and HIV infection. This reduces the risk of developing peripheral neuropathy with isoniazid.

Question 17

Latent TB treatment

Answer 17

For people, including those with HIV, aged younger than 65 years with evidence of latent TB who have been in close contact with people who have suspected infectious or confirmed active pulmonary or laryngeal drug-sensitive TB offer either of the following drug treatments:

• 3 months of isoniazid (with pyridoxine) and rifampicin, or
• 6 months of isoniazid (with pyridoxine).

Base the choice of regimen on the person’s clinical circumstances. Offer:

• 3 months of isoniazid (with pyridoxine) and rifampicin to people younger than 35 years if hepatotoxicity is a concern after an assessment of both liver function (including transaminase levels) and risk factors
• 6 months of isoniazid (with pyridoxine) if interactions with rifamycins are a concern, for example, in people with HIV or who have had a transplant.

Question 18

Active TB treatment

Answer 18

For people with active TB without CNS involvement, offer:

• isoniazid (with pyridoxine), rifampicin, pyrazinamide and ethambutol for 2 months, then
• isoniazid (with pyridoxine) and rifampicin for a further 4 months.

Modify the treatment regimen according to drug susceptibility testing.

For people with active TB of the CNS, offer:

• isoniazid (with pyridoxine), rifampicin, pyrazinamide and ethambutol for 2 months, then
• isoniazid (with pyridoxine) and rifampicin for a further 10 months.

Question 19

Active TB treatment - Adjuvant Corticosteroids

Answer 19

At the start of an anti-TB treatment regimen, offer people with active TB of the CNS dexamethasone or prednisolone, initially at a high dose with gradual withdrawal over 4–8 weeks

Question 20

In Active Pericardial TB offer

Answer 20

At the start of an anti-TB treatment regimen, offer adults with active pericardial TB oral prednisolone at a starting dose of 60 mg/day, gradually withdrawing it 2–3 weeks after starting treatment.