Clinical Uses of Antibiotics 5 - Monitoring and safety netting

What is meningitis?

Inflammation of the protective membranes that surround the brain and spinal cord (meninges). Can be bacterial, viral, fungal, or non-infective.

What is meningococcal disease?

Any infection with Neisseria meningitidis ‘meningococcus’.

Bacterial meningitis vs Meningococcal disease

Bacterial meningitis is any bacterial infection of the meninges, including Streptococcus pneumoniae, Haemophilus influenzae, Group B Streptococcus, and Neisseria meningitidis.

Meningococcal Disease is any illness caused specifically by the bacterium Neisseria meningitidis (also known as meningococcus). While this bacteria frequently causes meningococcal meningitis, it can also invade the bloodstream and cause life-threatening sepsis (blood poisoning or meningococcemia) without necessarily affecting the brain lining first.

When to suspect meningitis?

When patients show all 4 symptoms:

• Fever

• Headache

• Neck stiffness

• Altered level of consciousness

When to suspect meningococcal disease?

In people with any of these red flag symptoms:

• Haemorrhagic, non-blanching rash with lesions larger than 2 mm (purpura)

• Rapidly progressive and/or spreading non-blanching petechial or purpuric rash

• Any symptoms and signs of bacterial meningitis, when combined with a non-blanching petechial or purpuric rash.

Do not rule out bacterial meningitis just because a person doesn’t show any red flag symptoms.

Do not rule out meningococcal disease just because a person doesn’t have a rash.

What antibiotics can you give to someone with bacterial meningitis?

1^st line of treatment is IV ceftriaxone.

Ceftriaxone (covers most common causes of bacterial meningitis: Streptococcus pneumonia, Haemophilus influenza type b, Neisseria meningitidis, Group B streptococcal meningitis, NOT Listeria).

Add iv amoxicillin if risk factors for Listeria monocytogenes (risk factors: immunosuppressed, pregnant, over 60 years)

Cefotaxime may be used instead of ceftriaxone, like in babies with a history of jaundice.

If the patient with bacterial meningitis is not in the hospital and there is significant clinical delay in transfer to hospital, what can we give them?

IV or IM ceftriaxone or benzylpenicillin

If beta lactams have poor BBB penetration, why can they be used in treating bacterial meningitis?

Meningococcal inflammation helps BBB penetration.

After administering antibiotics to patient with an infection, what happens after 48hrs?

How does the patient feel?

Physical symptoms relevant to the infection (for example, shortness of breath in pneumonia should improve, though the cough can take time)

Take physiological parameters, like their blood pressure, heart rate, temperature, level of consciousness, to see if they’re all returning to normal.

Are there any possible complications arising, like is they renal function deteriorating?

Relevant blood tests to see in their WBC is decreasing, or their CRP count is decreasing (CRP is an inflammatory marker raised in infection and inflammatory conditions, like heart attack, rheumatoid arthritis. Normal level is below 5mg/mL)

If the patient is not getting better, there may be:

• Wrong antibiotic

• Antibiotic resistance

• Wrong diagnosis

• Complications of infection

• Adverse effect of antibiotic

• Superinfection (second infection)

• Opportunistic infection

What abbreviation do we use when reviewing antibiotics?

CARES

C = Cease antimicrobial prescription if there is no evidence of infection. (Consider alternative diagnoses).

A = Amend antimicrobials – ideally to a narrower spectrum agent – or broader if required – to ensure that treatment is effective and proportionate.

R = Refer to non-ward based antimicrobial therapy services for timely discharge from hospital and reduce risk of acquisition of healthcare-associated infection.

E = Extend antimicrobial prescription and document next review date or stop date.

S = Switch antimicrobials from intravenous to oral according to national intravenous to oral switch (IVOS) criteria

When reviewing from switching from IV antibiotics to oral, what do we do?

Perform a 48h review, then a daily review.

Use IVOS aid

When should IV antibiotic therapy be considered, and when might oral therapy be suitable?

IV therapy may be needed for:

• Deep-seated infections.

• Infections requiring high antibiotic concentrations in tissues.

• Infections requiring prolonged IV treatment.

• Critical infections with a high risk of mortality.

Oral therapy may be suitable in some cases, but an infection specialist should guide this decision.

Are steroids needed when using antibiotics?

Other treatment like steroids can be used to manage infections. Steroids can be given alongside antibiotics to reduce inflammation.

For example, IV dexamethasone is given for confirmed or strongly suspected bacterial meningitis to patients over 3 months old. We need to identify the causative organism. If the causative organism is S.pneumoniae or H.influenzae, continue dexamethasone. If its other organisms, stop dexamethasone.

If further investigations show that the patient does not have bacterial meningitis, the need for dexamethasone must be reassessed.

What are we monitoring antibiotics for?

We need to maintain that the antibacterial is effective therapeutically whilst preventing toxicity. Also, we need to monitor for side effects relevant to antibiotic.

What are the common and important side effects of antibiotics?

• Disrupted microbiome

• Hypersensitivity

• Red man syndrome

• Neurotoxicity and nephrotoxicity

• Bone marrow disorders

Disrupted microbiome when taking antibiotics

Antibiotic associated diarrhoea is relevant for all antibiotics, but particularly broader spectrum antibiotics. Includes C.difficile associated diarrhoea, which is especially a problem with aminopenicillins, cephalosporins, and clindamycin. Also includes candidal infections.

The best prevention of a disrupted microbiome is to avoid unnecessary use of antibiotics.

Hypersensitivity when taking antibiotics

Antibiotic hypersensitivity reactions include fever, hives and rash. Severe immediate reactions can include IgE-mediated anaphylaxis, which typically requires prior exposure.

• Particularly important with penicillins.

• A history of anaphylaxis, urticaria or an immediate rash after penicillin indicates a risk of immediate hypersensitivity. These patients should avoid penicillins and other beta-lactams as advised by relevant clinical guidance.

Red man syndrome when taking antibiotics

Red man syndrome is histamine mediated infusion reaction associated with vancomycin, causing an itchy red rash and flushing, and a potentially low blood pressure and angioedema.

Red man syndrome is more likely with rapid vancomycin infusion, so to prevent it, infuse vancomycin to reduce the risk.

Neurotoxicity and nephrotoxicity when taking antibiotics

Many antibiotics can cause kidney or nervous system toxicity.

• Gentamicin: Nephrotoxicity and ototoxicity.

• Vancomycin: Nephrotoxicity and, rarely, ototoxicity.

• Penicillins: Neurotoxicity, including seizures, especially in renal impairment.

• Chloramphenicol: Optic neuritis.

• Polymyxins: Nephrotoxicity and neurotoxicity limit their use, but they may be used for serious infections caused by selected aerobic Gram-negative bacteria when antibiotic options are limited due to antimicrobial resistance.

What bone marrow disorders can occur with antibiotics, and which antibiotics can cause them?

Some antibiotics can suppress bone marrow function, causing dangerously low white blood cell counts.

• Neutropenia: abnormally low levels of neutrophils.

• Agranulocytosis: a severe reduction in white blood cells, usually neutrophils, which can be life-threatening (mortality around 10% according to the lecture).

Examples of antibiotics that can cause these conditions include vancomycin, piperacillin–tazobactam and trimethoprim.

Monitoring white blood cell counts can help detect these adverse effects. A significant or sudden drop should prompt investigation.

What are some other important side effects of taking antibiotics do you need to be aware of?

• Cardiac arrhythmias

• Cholestatic jaundice

• Hepatotoxicity

• Some specific to pregnancy/ breastfeeding/infants e.g. chloramphenicol – Grey baby syndrome (abdominal distention, haemodynamic collapse, grey skin). Tetracyclines should not be given to pregnant women (skeletal development, maternal hepatotoxicity)

• Check for interactions e.g. erythromycin + statins à  risk of myopathy (hold the statins).

What are some visible changes that may occur when taking antibiotics?

Rifampicin can cause an orange red colour to sections

Metronidazole can cause red/brown urine

Doxycycline can cause photosensitivity and deposition in bones and teeth.

What is chemoprophylaxis?

Antibiotic treatment aiming to prevent disease

What are notifiable diseases?

Any medical condition that doctors, laboratories, or veterinarians are legally required to report to government or public health authorities.

Bacterial meningitis and meningococcal disease are both notifiable diseases. All suspected cases must be reported to your local Health Protection Team.

How do we safety net with patients?

We can’t follow up eery patient we see, so we need to advise people on what to do if their condition deteriorates, does not improve within a certain time, or if they develop adverse effects as a result of treatment.