M11 Clinical Therapeutics Problem Based
Master BA is a 26 month old boy who has been admitted to the Emergency Administration Suite (EAS) with fever weakness and vomiting. He has developed a rash on the trunk of his body and his wrists and ankles and his GP's recommended urgent referral. Benzylpenicillin 600mg IV was given immediately before transfer to hospital.
The table below shows Master BA treatment record:
Time of Administration
Drug and Dose Given
Route of Administration
Direction of Given
Before administered to Hospital
Benzylpenicillin 600mg
Intravenous (IV)
Immediately
(stat)
On admission hospital
(Empirical treatment)
Cefotaxime 675mg
Intravenous (IV)
One every 8 hours
After 48 hours of admission hospital
Ceftriaxone 1g
Intravenous (IV)
One daily
On the admission, Master BA's was weighed as 13.5kg. The empirical antibiotic therapy with Cefotaxime 675mg IV was given to Master BA before getting the laboratory result including blood, cerebrospinal fluid (CSF) culture, urea and electrolytes (U&E's) and full blood count (FBC). The Ceftriaxone was replaced after 48 hours most likely when the laboratory results returned.
The table below shows the laboratory results on admission (Kumar and Clark, 2006):
Test
Test Result
Normal Ranges
Normality
Laboratory Culture
(Blood and CSF)
Neisseria Meningitides
No bacteria, CSF clear and no increased neutrophils
CSF appearent cloudy and contain neutrophils ++
Haemoglobin
12g/dL
13.5-17.7g/dL
Normal
White blood cell
14 x109/L
4.0-11 x109/L
High
Neutrophils
8 x109/L
2.0-7.5 x109/L
High
Platelets
10 x109/L
150-400 x109/L
Low
CRP
48mg/L
<10mg/L
High
ESR
72mm/hr
<20mm/hr
High
U&E s
No abnormalities detected
Other concern in this case, Master BA has an older brother who is 8 years old and his mother is currently 21 weeks pregnant.
Meningitis is an inflammation of the membranes covering the brain and spinal cord. The membranes also known as meninges which are help to protect the brain from injury and infection. (Meningitis Research Foundation, 2010) The meningitis caused by a wide variety of micro-organisms includes virus, bacteria, fungi and non infective such as complication of head injury or drug implicated. The most common cause of meningitis in children and young adults in UK is bacterial infection from meningococcal meningitis (eg: Neisseria meningitides), haemophilus influenza, streptococcus pneumonia bacteria. (Nudelman & Tunkel, 2009 and Ginsberg, 2004) Every year around 2500 cases of bacterial meningitis occur in the UK, around 10% of cases result in death and 15% of those who survive meningitis are left with severe complications. (Ramsay et al., 1997; Fortnum and Davis, 1993) Meningitis kills more UK children under the age of five and 25% in 15 to 19 year olds. (Health Protection Agency, 2011; Trotter et al., 2006) Meningitis develops rapidly and presents different symptoms in young children such as fever, petechial pupural rash, photophobia, stiff neck, and vomiting and loss appetides. (Kumar and Clark, 2006) Meningitis can damage the brain and cause long term complications such as deafness, seizures, arthritis developmental delay or learning disabilities and paralyzed muscles if delay to treat the meningitis. (Kaplan and Di Pentima, 2010)
From Master BA's blood and CSF cultures tested positive for neisseria meningitides. Neisseria meningitides are a heterotrophic gram-negative diplococcal bacterium and contain twelve groups (serogroups) of neisseria meningitides and five responsible for the majority of cases of invasive disease in humans such as A, B, C, Y and W-135. (Kaplan and Pentima, 2010) Neisseria meningitides is normal inhabitant of the human nasapharynx and will be transmitted from person to person by droplets or secretion from the upper respiratory tract. Normally, spread between individuals with close contact or crowded environments such as daycare, schools, colleges etc. The most common case in UK is neisseria meningitides (serogroup B) about 90% of all case. (Kav, 1995; Health Protection Agency, 2011) The pathogenesis and pathophysiology of bacterial meningitis start from the colonisation of nasopharyngeal mucosa then progression to meningeal invasion of the subarachnoid space causing inflammation. (Tunkel and Scheld, 1993; Apicella, 2010)
The neisseria meningitides is diagnosed from presenting symptoms such as fever, petechial rash, stiff neck and vomiting. For Master BA before admission to hospital, his GP could have used glass tumbler to test the nature of rash. The glass or tumbler test must be done with young people with suspected bacterial meningitis. (NICE, 2009; Hart and Thomson, 2006; Parikh and Maconochie, 2003)
The Glass or Tumbler Test
The glass tumbler test can be performs at whole body by placing a glass tumbler firmly against a rash, if the rash through the glass (non blanching rash) then the test is positive should admin to hospital immediately. For those who have dark skin harder to see through should check at paler areas. (Meningitis Research Foundation, 2010)
In the hospital, meningitis normally confirm by CSF examination and blood count. (SIGN, 2008) For Master BA, the CSF sample will be taken by using lumbar puncture. (Shlamovitz, 2010) The CSF test result abnormalities in meningitis include appears turbid, decreased glucose concentration and increased protein concentration. Master BA is appeared cloudy and this shows that he got meningitis. (Gary and Fedorko, 1992; Gondim, 2009) However, the CSF sample may not culture if antibiotics have been administrated, so there will be alternative test for Master BA is polymerase chain reaction (PCR) analysis to confirm the diagnosis. This PCR is a rapid and sensitive test that not affected by prior antibiotic treatment. The PCR is a test that performed by using DNA sequencers to detect the bacteria and result will show in 2 hours. (Gondim, 2009)
The Lumber Puncture Test:
(Discovery Health, 2005)
The lumbar puncture procedure, a needle is put between the vertebrae (back bones) of the lower spine and draws out some of the fluid surrounding the spinal cord. The test will not perform if the infection on the skin area that needle will enter. The position during lumber puncture will be lie on one side with legs pulled up and chin tucked down, so that the spine is curved and allow the needle get in more easily. The area of skin at the base of spine will be painted with an antiseptic solution and local anaesthetic to numb the area for injection. Then, a hollow needle will be injected in between two of the vertebrae and into the space around the spinal cord and sample of CSF collected. (NHS Clinical Knowledge Summaries, 2011)
The Master BA's blood result indicates that he has increase in white blood cell and neutrophillia which might due to immune response to an infection. The C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are indicate that some non specific of inflammation. The platelet count for Master BA is low contributing to his meningococcal petechial rash. (Meningitis Research Foundation, 2010 and García et al., 2008) From the overall blood result and presenting symptoms prove that Master BA is having bacterial meningitis.
Other new method of diagnosis such as aspirate skin lesion scraps testing, throat swabs and antibody test can help to diagnose in meningitis infection. However, this new diagnosis method still being developed and might provide some benefit even though this diagnosis method have not established the 'gold standard' and standardised test range. (SIGN, 2008)
The empirical treatment with I.V broad spectrum antibiotic is an early treatment that initiated immediately to any patient suspected with meningitis prior to transport to hospital. (Nudelman and Tunkel, 2009) This is also known as a 'blind treatment' to prevent the serious type of bacterial meningococcal infection that can cause high risk of death to patient. According to NICE and SIGH guideline benzylpenicillin sodium is the first line and cefotaxime for patient who have history of penicillin allergy. If patient has history of penicillin and cephalosporins should be give chloramphenicol. (BNFC 2010)
Benzylpenicillin (Penicillin G) is effective against meningococcal infections. It is an effective broad spectrum antibiotic for unknown bacterial meningitis such as gram -positive bacteria that contain beta-lactamases. (Health Protection Agency, 2011) This can be given as I.V injection or infused over 15-30 minutes using glucose 5% or sodium chloride 0.9% solutions for dose of 50mg/kg or more. (BNFC 2010) Before admitted to hospital, benzylpenicillin 600mg I.V was given to Master BA by his GP. This is an appropriate drug for empirical therapy. On admission to hospital, after taking blood sample for laboratory test and body weight cefotaxime 675mg I.V every 8 hours.
The initial antibiotic treatment is still empirical ('blind') while waiting for patient's laboratory result. The antibiotic treatment should be given and must take into account the possible causative pathogens, patient's age and local antibacterial resistance. (SIGN, 2008) After the pathogens have been confirmed, the specific treatment should be given to clear the infection.
The 3rd generation of cephalosporins such as cefotaxime and ceftriaxone are highly recommended for treatment of neisseria meningitides. (SIGN, 2008; Vázquez, 2007 and Nudelman and Tunkel, 2009) Second lines therapies will be considered on day 2 depend on the patient's condition. The combination of 2 to 3 antibiotics such as rifampicin, ciprofloxacin and other penicillin based antibiotics can be tried. If the patient's condition is getting worse intensive care can be considered. (SIGN, 2008; Vázquez, 2007; Sariangue et al., 2009)
The 3rd generation of cephalosporins is normally given to children for meningococcal infection in UK. However, there is a potential risk of an incompatibility between ceftriaxone sodium with other calcium containing parental solutions due to ceftriaxone calcium precipitation. This can cause significantly cardiopulmonary risks and limits the use of calcium containing parental nutritional supplements. So, ceftriaxone should be used after 48 hours and no calcium contain products have been used. (SIGN, 2008; Bradley et al., 2009 and Nakai et al., 2009) Cefotaxime sodium is 3rd generation of cephalosporins for broad spectrum antibiotic activity against gram-negative and gram-positive bacteria. It must be avoid for patient who is hypersensitivity reaction to penicillins. Same class and indication as cefotaxime, ceftriaxone is caution to patient who has renal or hepatic impairment. Monitoring of plasma concentration and reduce dose might needed. (BNF 60 and BNFC 2010)
Master BA's initial treatment was cefotaxime 675mg every 8 hours via intravenous route this is appropriate and safe for his condition.
Calculation of Cefotaxime for Master BA:
Weight of Master BA = 13.5kg
Total daily dose of Cefotaxime = 50mg/kg every 8-12 hours (Max. 12g daily)
Dose calculates for Master BA:
Single dose: 50mg x 13.5kg = 675mg every 8hours
Total Daily dose: 675mg x 3 doses per day = 2.025g
So, the dose is safe for Master BA because the total daily dose is only 2.025g and not over the maximum total dose for daily is 12g. (BNFC 2010)
After 48 hours cefotaxime 675mg I.V was discontinued and replaced with ceftriaxone 1g once daily via I.V route. The reason of switching antibiotics might because of ceftriaxone is able to treat and prevent reoccurring secondary infection by neisseria meningitides. (BNFC 2010) The once daily dose of ceftriaxone IV might be more acceptable and convenient to Master BA's parents compare to cefotaxime 3 times dose per day via injection by nurse to their young child. Both cefotaxime and ceftriaxone are 3rd generation cephalosporins which have similar nature, so is unlikely affect any worse condition for Master BA.
Ceftriaxone treatment should be continue for the remaining 5 five of total seven day antibiotic treatment course and extend to total ten days treatment course if the infection not cleared yet. For Master BA's condition, the ceftriaxone is appropriate and safe for administration. (SIGN 2010)
Calculation of Ceftriaxone for Master BA:
Weight of Master BA = 13.5kg
Total daily dose of Ceftriaxone = Maximum 80mg/kg once daily by intravenous infusion only.
Max daily dose = 80mg x 13.5kg = 1080mg (1.08g)
The total once daily dose that given to Master BA is 1g, which is less than the maximum daily dose and it's safe and appropriate to be given. (BNFC 2010)
Supportive care should be given to Master BA to improve his quality of life during the treatment. This can help Master BA to increase the chance of survivability by improving the immune system more easily for overcoming the infection. According to SIGN guideline, fluid replacement therapy should be given to maintain the organ perfusion and prevent septic shock. Since Master BA was vomiting so rehydration should be given to him. The dose that should be given is 20mL/kg bolus repeatedly and increasing to 60mL/kg bolus. Additional of isotonic and colloid solution should be used to increase body concentration more rapidly. Master BA should maintain high fluid intake for possible antimicrobial- induced bacteria lysis and the concentration of U&Es should be monitored. This can prolong the morbidity and mortality of Master BA's condition. (Nudelman & Tunkel, 2009) To stop the nausea and vomiting, cyclizine suppositories (12.5mg up to three times daily) can be given to Master BA. However, the common side effect such as drowsiness, GI disturbances must be aware. (BNFC 2010)
Pyrexia and pain therapy should give to Master BA due to his fever. The normal range of body temperature is 37°C and Master BA should maintain his body temperature. The body temperature can be monitored directly via rectal route. However, due to the infection Master BA might suffer headaches and pain so child dose paracetamol (120-250mg every 6 hours) or ibuprofen (100mg three times daily) can be given to him to control both fever and pain. (BNFC 2010)
Corticosteriods are used in meningitis because of their anti-inflammatory effect. In children, meningococcal meningitis will reduce the neurological disability or reduce hearing. Some studies find out that use of corticosteroids can reduce the rate of incidence but some of the meta-analysis data show that dexamethasone no clinical benefit and unable to reduce the rate of neurological disability. (Van de Beek et al, 2010, Grimprel, 2009, Peltora et al, 2007) Only few studies prove that dexamethasone can be use in severely ill patient. (Ndreu et al., 2009, Vardakas et al., 2009) More studies and conclusive evidence in this area might need to find out.
Simple emollients such as calamine cream can be given to Master BA used to soothe the skin and relief the itchiness.
The follow up care such as hearing test should be performed in hospital along with an assessment of neurological or psychiatric problem, renal impairment, orthopaedic and skin complication. If any of these problems detected then rehabilitation, appropriate academic and support group can be contacted to help to recovery. Master BA also should reassess within 4 weeks for any signs of development delay such as not walking and talking after treated meningitis infection. (Kaplan and Pentima, 2010, SIGN, 2008, National Deaf Children's Society, 2010)
Prophylaxis treatment should be considered for Master BA's 8 years old brother and his mother who is currently 21 weeks pregnant because of prolong contact with him. Other people such as nannies might have come into household contact with Master BA during the 7 days before diagnosed. Prophylaxis treatment is necessary for prevent the spread because meningococcal bacteria is highly infectious. It might easily to spread via dispersed droplet particle because the bacteria are able to stay inside the nasopharyngeal cavity after the bacteria has been treated. (Chang et al., 2003, SIGN, 2008) The prophylactic antibiotic includes high single dose or short course of rifampicin, ciprofloxacin (unlicensed) and ceftriaxone (unlicensed) should be given within 24 hours after diagnosis. Master BA's 8 years old brother should be given rifampicin by mouth 10mg/kg (max. 600mg) every 12 hours for 2 days. Rifampicin must be contra indications with people who have jaundice and due to many interactions so must check whether Master BA's brother taking any other medication. For Master BA's 21 weeks pregnant mother, ceftriaxone 250mg intramuscular injection (I.M) as single dose can be given to her. (BNF 60 and BNFC 2010)
Calculation of Rifampicin for 8 years old brother:
Estimate brother's weight 25kg
Dose: 10mg/kg (single dose) x 25kg = 250mg
So, the prophylactic dose for 8 years old brother is 250mg every 12 hours (Twice daily) for 2 days. (BNFC 2010)
For the common type of meningococcal which is serotype B still no vaccine available for it now. However, there is vaccination for meningococcal polysaccharides A, C, W135 and Y should be administrated after meningitis treated and given to children over 2 year old. (Pace and Pollard, 2007, SIGN 2008)
In conclusion, Master BA has a meningococcal infection that caused by neisseria meningitides. He was given appropriate treatment which is benzylpenicillin (antibiotic) by his GP before administered to hospital. Diagnosis was confirmed in hospital then cefotaxime given at first then change to ceftriaxone after 2 days. This may be due to risk of calcium interaction and reduce frequency of the dosing regimen. Master BA should continue his treatment for 5 more days until the infection is clear if still not clear continue his treatment up to 7 days. He will need to return for a follow up within 1 month after discharge. His mother and brother should receive prophylaxis antibiotic treatment within 24 hours of diagnosis.
