Case Report: Role of Ampicillin in Empirical Treatment of Bacterial Meningitis in AdultsFang Zhe Haw

Case Report

Role of Ampicillin in Empirical Treatment

of Bacterial Meningitis in Adults

Fang Zhe Haw

Department of Pharmacy
Sarawak General Hospital

Abstract
This report presents the significance of using Ampicillin to treat bacterial meningitis. An
elderly patient treated with intravenous Ceftriaxone monotherapy was experiencing
temperature spikes and increasing trend of total white cell counts. With the addition of
intravenous Ampicillin, clinical improvement was observed. The result shows that antibiotic
treatment of bacterial meningitis should take into account the possibility of a wider range of
potential pathogens. Therefore, a range of possible organisms should be considered during
the selection of antibiotics to be used to achieve optimal outcome. Essentially, the use of
intravenous Ampicillin may be advantageous for treatment of bacterial meningitis in adults,
especially in those aged 50 years and above since they are at higher risk of developing
Listeria monocytogenes meningitis.

Keywords: Intravenous Ampicillin, Bacterial Meningitis

Introduction
Meningitis is an inflammatory disease of the leptomeninges, the tissues surrounding the
brain and spinal cord.¹ Bacterial meningitis reflects infection of the arachnoid mater and the
cerebrospinal fluid (CSF) in both the subarachnoid space and the cerebral ventricles.¹ The
most common clinical features include severe headache, fever, stiff neck and nausea.¹ Less
common manifestations are seizures, coma, cranial nerve palsy, rash and papilledema.¹

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 Case Report: Role of Ampicillin in Empirical Treatment of Bacterial Meningitis in AdultsFang Zhe Haw

This report presents a case of improving bacterial meningitis after the addition of intravenous
Ampicillin to the ongoing antibiotic regimen of intravenous Ceftriaxone. The patient
experienced temperature spikes and presented with increasing trend of total white cell
counts (TWCC) while being treated by intravenous Ceftriaxone monotherapy during the first
few days of admission. As a result, intravenous Ampicillin 2g four-hourly was added as part
of the management in which the TWCC was in decreasing trend and patient became afebrile.
The Ampicillin was administered for a total duration of five (5) days.

Case Presentation
A 84-year-old Malay male was admitted to the Medical 3 Ward on 9 June 2020 on an
impression of likely bacterial meningitis. His chief complaint was prolonged fever,
accompanied with chills and rigors as well as stiff neck. He also appeared to be less
responsive and had poor oral intake for the past one week. His past medical history included
diabetes mellitus, hypertension, dyslipidaemia, anterior shoulder dislocation and history of
admission for urosepsis. No family history of malignancy. Non-smoker and non-alcoholic. No
known drug and food allergies. At the time of admission, he was febrile, TWCC of 15.2 and
blood pressure of 132/86mmHg.

Several tests were performed to investigate the cause of the sepsis with altered mental state.
Computerised tomography (CT) scan of the brain showed hypo-density of right cerebellum,
which may be caused by diffuse parenchymal cerebellar oedema and/or infarction.² Lumbar
puncture (LP) was performed on this patient under aseptic technique with opening pressure
of less than 20 cm H2O. The extracted CSF was clear and sent for various tests such as
biochemistry, culture and sensitivity, Latex Agglutination, Indian-ink and GeneXpert.

In terms of biochemistry, the patient’s CSF protein, glucose, plasma glucose ratio and Gram-
stain were analysed. The CSF protein was 2.986 g/L (normal: 0.15-0.45 g/L), suggesting it
could be bacterial or tuberculous (TB) meningitis. CSF plasma glucose ratio was 0.25
(normal: >0.66), suggesting it could be bacterial, viral and TB meningitis. Gram-stain result
showed no organism. However, Gram stain may be negative in up to 60% of cases of
bacterial meningitis, even without prior antibiotics.³ Negative results were recorded in both
Latex Agglutination and Indian-ink tests, suggesting the infection caused by Cryptococcal
spp. was unlikely. Furthermore, both culture and sensitivity (C&S) test for CSF and blood
showed no growth. Negative results also recorded for multiple tests of nasogastric aspirate

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 Case Report: Role of Ampicillin in Empirical Treatment of Bacterial Meningitis in AdultsFang Zhe Haw

for acid-fast bacilli (AFB). CSF GeneXpert also did not detect the presence of M.
tuberculosis. In addition, blood culture and sensitivity test showed no growth.

Despite receiving intravenous Ceftriaxone treatment for four (4) days, patient’s TWCC was in
increasing trend, and peak at 20.43 x 109 cells per litre. In between this period, several
temperature spikes were also observed; otherwise he was comfortable and tolerating
nasogastric tube (NG) feeding well. In consideration of the persistent bacterial meningitis,
intravenous Ampicillin 2g four-hourly was added on Day 5 of Ceftriaxone treatment. As a
result, the patient was clinically improving in which he became afebrile and TWCC returned
to its normal range. After five (5) days of initiation, intravenous Ampicillin was ceased,
leaving only intravenous Ceftriaxone on board. He was then transferred to Pusat Jantung
Sarawak for rehabilitation and continuation of antibiotic treatment.

Discussion
In this report, we described the role of Ampicillin in the empirical treatment of bacterial
meningitis, particularly when the infection was not managed adequately by Ceftriaxone
monotherapy. Empirical antibiotic treatment of bacterial meningitis in immunocompetent
adults should take into account the possibility of a wider range of potential pathogens.⁴
According to the National Antimicrobial Guideline 2019 of the Ministry of Health Malaysia,
the common organisms causing acute bacterial meningitis include Streptococcus
pneumoniae, Neisseria meningitidis and Haemophilus Influenzae in which the preferred or
first-line treatment is intravenous Ceftriaxone 2g 12-hourly to target these pathogens
effectively.⁵

Individuals over aged 50 years are at increased risk of Listeria monocytogenes meningitis. ⁶
Listeria monocytogenes is a gram-positive facultative intracellular bacteria transmitted to
humans through ingestion of contaminated food, in particular ready-to-eat food, products
with a long shelf life, deli meats and soft cheeses.⁶ The clinical symptoms of Listeria
meningitis are non-specific and similar to those of other causes of meningitis and first-line
treatment with third-generation cephalosporins is ineffective.⁶ Awareness of this pathogen is
therefore crucial, to enable adequate treatment to be started and the best outcome to be
achieved. Empirical cover for this organism should be considered, especially when the
course of disease is indolent.⁵ For this reason, adults above 50 years of age should receive
intravenous Ampicillin which possesses antimicrobial activity against Listeria
monocytogenes as part of the empiric regimen.⁷,⁸ The European Society of Clinical
Microbiology and Infectious Diseases (ESCMID) Guidelines has also supported the use of

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 Case Report: Role of Ampicillin in Empirical Treatment of Bacterial Meningitis in AdultsFang Zhe Haw

Ampicillin as the standard in-hospital treatment for community-acquired bacterial meningitis

to cover for the aforementioned common organisms.⁹

Specifically in the case of Neisseria meningitidis isolates, the great majority are susceptible
to Ampicillin, although strains with reduced susceptibility have been reported in Europe,
South Africa, and the United States. Nevertheless, such resistant strains usually respond to
the standard high dose of Ampicillin recommended for meningitis.⁷

The antibiotic treatment should be continued for a total of fourteen (14) days despite no
organism can be isolated from CSF C&S; however, LP is suggestive of bacterial meningitis
and patient is responding towards the treatment, as seen in this case.⁵

Lumbar puncture is essential for diagnosis, as blood cultures are often negative.⁶ CSF gram-
staining could be negative at the first LP in which one study reported only 24% of patients
with Listeria monocytogenes meningitis were revealed by this test.¹º Meanwhile, a high
proportion of adults with Listeria monocytogenes meningitis had atypical CSF findings; 23%
of the patients had no individual CSF findings indicative of bacterial meningitis.¹º Repetition
of the CSF analysis is therefore advised in cases of bacterial meningitis that do not improve
with first-line antibiotic treatment where no specific organism was identified on initial
evaluation.⁶

Conclusion
Awareness and recognition of the infection risk by any possible organisms, especially in
elderly patients, are essential to provide the most effective empirical treatment in bacterial
meningitis. LP and CSF findings do not necessarily provide the entire information regarding
the causative pathogens in which treatment based on clinical judgment and experience may
play a role too. For patients who aged above 50 years of age, the usual recommended
empirical treatment should be re-evaluated for which the risk of Listeria monocytogenes
meningitis is present. As a result, the administration of intravenous Ampicillin, alongside with
intravenous Ceftriaxone, in empirical treatment of acute bacterial meningitis is of beneficial
to cover a wider spectrum of organisms.

Abbreviations

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 Case Report: Role of Ampicillin in Empirical Treatment of Bacterial Meningitis in AdultsFang Zhe Haw

AFB acid-fast bacilli; CSF cerebrospinal fluid; CT computerised tomography; C&S culture
and sensitivity; LP Lumbar puncture; NG nasogastric tube; TB tuberculous; TWCC total
white cell counts

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