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bacterial encapsulation is a signicant virulence factor for nasopharyngeal colonization and systemic invasion of pathogens [12]. The polysaccharide capsules of the
primary meningitis pathogens, including S. pneumoniae, N. meningitidis, Hib,
GBS, and E. coli, inhibit phagocytosis by preventing the accumulation of adhesins
such as complement factors [12].
Bacterial entry into the subarachnoid space is facilitated by the intensity and
duration of circulating bacteria, the virulence of the microorganisms, and the degree
of host defense deciency, such as immunodeciency. Also, it occurs through the
interaction of bacteria with endothelial cells forming the blood–brain barrier (BBB).
In Hib and S. pneumoniae meningitis, evidence exists that the initial bacterial entry
site into the ventricle and spread to the CSF may be the choroid plexus [12–14].
Although some structural differences exist between the lipooligosaccharide
(LOS) of N. meningitidis and the lipopolysaccharide (LPS) of gram-negative bacilli,
both generally contribute to infection by a similar pathogenetic mechanism.
Lipooligosaccharide is commonly found in gram-negative pathogens such as pathogenic Neisseria spp., H. inuenzae types, Haemophilus ducreyi, Moraxella spp.,
and Bordetella spp. that infect non-enteric surfaces. The oligosaccharide portions of
the LOS contain structures that mimic human tissue antigens (e.g., paragloboside,
pk, i antigen, Lewis X, and sialyl-Lewis X) [15]. Lipooligosaccharide interacts with
various cells, including neutrophils, macrophages, and endothelium, to initiate the
release of inammatory mediators of shock state, mainly tumor necrosis factoralpha (TNF-α), interleukin (IL)-1, IL-6, and interferon-gamma (IFN-γ). Symptoms
of meningococcal sepsis are caused by LOS, which acts as an endotoxin and activates proinammatory cytokine pathways of the host [16].
The highest plasma levels of endotoxin measured in sepsis have been demonstrated in patients with meningococcemia. The ability of the organism’s outer membrane to scatter heavily into bubbles or vesicle-like structures is a signicant factor
in producing these high endotoxin levels. Although the endotoxin release in the
membrane bleb form is highest in meningococci, it was also documented in several
other gram-negative bacteria, including Salmonella, Shigella, E. coli, Citrobacter,
and Haemophilus spp. [16].
Immunoglobulin and complement are at very low levels in CSF, at concentrations nearly 1000 times lower than in serum, resulting in poor opsonic activity in
CSF.After the invasion of CSF, bacteria can multiply to high concentrations (up to
107 organisms/mL) within hours due to insufcient humoral immunity in CSF [12].
When inammation begins, cerebrovascular autoregulation and vasogenic edema
occur; intracranial pressure increases due to the separation of tight junctions
between cells in the BBB endothelium [12, 17].
E. Yeşil et al.
31.5 Clinical Features
In many children with ABM, fever and meningeal inammation symptoms develop.
Some children with ABM present fulminant meningitis symptoms and signs rapidly
within a few hours. The fulminant course is often complicated by severe cerebral
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edema. If meningitis develops after VPS, pilonidal sinus, or adjacent tissue infections, such as mastoiditis, initial respiratory tract infection ndings may not be
prominent.
The clinical features and treatment of ABM show signicant differences in newborns, preterm infants, postneonatal infants, and children.
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31.5.1 Clinical Features inNewborns andPremature Infants
Clinical ndings of ABM in newborns and preterm infants may not differ from sepsis without meningitis and may be very similar. Therefore, the possibility of ABM
should be kept in mind in every neonatal sepsis case. Decreased activity, poor feeding, difculty in sucking, respiratory distress, temperature irregularities, fever (rectal temperature >38 °C more common in term infants), hypothermia (rectal
temperature <36°C more common in preterm infants), neurological ndings such
as decreased tone, irritability, sleeplessness, inclination, and convulsions are the
most common clinical ndings [17].
Neonatal meningitis is also more likely to have other intracranial and neurological complications, such as hydrocephalus, than other age groups. However, even in
newborns with neurological complications, symptoms and physical examination
ndings may be very ambiguous, so these babies should be evaluated frequently and
carefully by experienced pediatricians. If necessary, imaging studies should be performed for complications in suspected cases.
Laboratory ndings may accompany sepsis-related laboratory ndings such as
blood culture positivity, leukocytosis, leukopenia, neutrophilia, neutropenia,
increased immature/total white blood cell ratio, thrombocytopenia, and elevated
c-reactive protein (CRP) and procalcitonin levels. In addition, abnormal CSF ndings may be seen, including pleocytosis, increased neutrophil count, increased protein and low glucose concentrations, bacteria on Gram stain, and CSF culture
positivity. Transfontanel ultrasonography (US), contrast-enhanced computed
tomography (CT), or contrast-enhanced magnetic resonance (MR) imaging are recommended for neurological complications.
31.5.2 Clinical Features inPostneonatal Infants andChildren
Infants with ABM mainly present clinical ndings such as fever or hypothermia,
irritability, lethargy, poor feeding, vomiting, bulging fontanel, and seizures. Children
and adolescents may present clinical ndings, including fever, headache, vomiting,
irritability, confusion, lethargy, neck stiffness, and photophobia [5]. Fever, seizures,
and vomiting are the most common ndings in children with ABM [18, 19]. Also,
in the study of Amorilyo etal. [19], photophobia was highly specic (88%) but
lowly sensitive (22%) for meningitis.
Generally, upper respiratory tract infection symptoms and signs begin before
meningeal symptoms. Previous oral antimicrobials do not change the clinical
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manifestations of meningitis. Children with ABM often appear restless and sick.
Vital sign anomalies such as tachycardia and tachypnea may be seen, especially
in young children. Meningeal symptoms, including neck stiffness, and Kernig’s
and Brudzinski’s signs, are present in many children with ABM at presentation [5].
In physical examination, signs of increased intracranial pressure (IIP), seizures,
and other focal neurological ndings may be seen in addition to irritability, confusion, and lethargy. The level of consciousness at presentation may range from irritability, confusion, and lethargy to coma associated with poor prognosis and adverse
neurological outcomes [5]. While symptoms have been occurring, the signs of meningitis may not be fully established yet; however, pleocytosis and other CSF ndings compatible with ABM may exist.
Seizures mainly occur before or within the rst 48 h of hospital admission in
about 20–30% of patients with ABM [20]. Usually, generalized seizures are seen.
Later, focal seizures indicating cerebral damage may occur [5]. In a study, seizures
were present in 92.5% of 361 children with ABM [18].
Bulging fontanelle and diastasis of the cranial sutures may occur in infants with
IIP.Other clinical IIP signs may not be apparent in infants with open fontanelles. In
a study on children with suspected meningitis, bulging fontanelle was present in
50% of children with meningitis and had a positive predictive value of 38% [19]. On
the other hand, in older children with closed fontanelles, vomiting, headache, and
consciousness changes may be seen earlier with IIP.Cushing’s triad, composed of
bradycardia, hypertension, and respiratory irregularity, indicating cerebral herniation, is a late manifestation. Involvement of the third, fourth, and sixth cranial nerves
and papilledema, a rare nding in ABM, also suggest IIP. If papilledema occurs,
complications such as sinus vein occlusion, subdural empyema, or brain abscess
should be investigated [5].
Motor abnormalities, including asymmetrical or absent tendon reexes, hemiparesis, quadriparesis, and consequences of cranial nerve injuries such as facial asymmetry, eye deviation, extraocular movements, abnormal pupillary light reexes, and
visual eld defects, may be seen as focal neurological ndings, generally as late
complications of meningitis [5]. A study involving 235 children with ABM, aged
4days to 18years, mean 26months, followed for 1 year, reported that 10% of the
cases had focal neurologic ndings at presentation. Focal neurologic ndings at
admission were associated with an increased risk of permanent neurologic and cognitive abnormalities 1 year after discharge [21].
In children with ABM, serious complications such as disseminated intravascular
coagulation (DIC), septic shock, pericardial effusion, acute respiratory distress syndrome, septic arthritis, and reactive arthritis may accompany the clinical picture,
primarily due to bacteremia. Skin eruptions like petechiae and purpura may occur
mostly in ABM caused by N. meningitidis. Lesions are more prominent on the
extremities following an erythematous maculopapular rash [5]. Patients may also
have continuing infections such as sinusitis, facial cellulitis, otitis media, pneumonia, or arthritis [2, 5].
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31.6 Laboratory andRadiological Evaluation
31.6.1 Blood Tests
In cases with suspected ABM, complete blood count, glucose, serum electrolytes,
creatinine, blood urea nitrogen, inammatory markers such as CRP and procalcitonin, coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) should be analyzed.
Blood cultures are positive in approximately 67–86% of cases with ABM [22, 23].
About 50% of adult patients with gram-negative bacillary meningitis may have bacteremia before the clinical manifestation of meningitis [5, 24].
31.6.2 Cerebrospinal Fluid Evaluation
The denitive diagnosis of meningitis is made by CSF evaluation. In practice, lumbar puncture (LP) indication arises when meningitis is considered clinically. If CSF
ndings suggest ABM, empiric antibiotics should be started immediately [5].
31.6.2.1 Contraindications forLumbar Puncture
Cardiopulmonary failure, gushing vomiting episodes, IIP, papilledema, cranial
nerve involvements suggesting IIP, and skin infection over the LP region are the
primary contraindications for LP.Clinical ndings related to IIP should be investigated before performing LP. And especially in older children with closed fontanelles, CT is an appropriate method to exclude pre-LP IIP or an intracranial
space-occupying mass such as a brain abscess or tumor. Lumbar puncture should be
performed immediately after imaging if an IIP nding or an intracranial mass lesion
is not visualized [5].
Antimicrobial treatment should not be delayed because of the need for cranial
imaging and contraindication for LP.Blood samples for tests and cultures should be
taken immediately, and empirical antibiotics administered. A single dose of antibiotics administered before LP does not signicantly alter CSF leukocyte count, protein, or glucose and may slightly reduce rates but generally does not affect CSF
Gram-staining and culture results [5, 25].
The probability of detecting bacteria in Gram-staining may be pathogen related. In
pneumococcal meningitis, approximately 80–90%, and in meningococcal meningitis,
70–80% of pediatric patients have positive CSF Gram-staining. But, CSF Gramstaining is positive for half and one-third of the patients with gram-negative bacillary
and Listeria spp. meningitis, respectively [5]. O Gram-stained smears, gram-positive
diplococci suggest S. pneumoniae, small pleomorphic gram-positive cocci, and coccobacilli GBS, gram-positive bacilli and coccobacilli L. monocytogenes, gram-negative diplococci N. meningitidis, and gram-negative coccobacilli H. inuenzae.
Although Gram-staining helps estimate the causative pathogen, broad-spectrum antibacterial treatment should be continued until CSF culture results are obtained [5].
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More than 50% of adult patients with gram-negative bacillus meningitis have the
bacilli on Gram-staining [24]. In a study of 66 patients with culture-proven gramnegative meningitis in children, CSF Gram-staining was positive in 61% of the
cases [1]. Gram-staining was negative in all patients with sterile CSF cultures in the
same case series. In rare cases, CSF Gram-staining results may be false-negative or
false-positive; therefore, a negative or positive Gram-staining result, although
important, should not be the only guide for empirical treatment [2, 24].
31.6.2.2 Cerebrospinal Fluid Examination
In CSF examination, cell count, cell distribution, glucose and protein concentrations, Gram stain, and culture should be seen. Typically in ABM, increased CSF
pressure (>25 cm H2O), neutrophilic pleocytosis (>100/cubic millimeter [mm3;
microliter, μL] usually thousands, usually >50–70% polymorphonuclear leukocyte
[PMN]), low glucose (<40mg/dL or CSF/serum glucose ratio<40%), elevated protein (>45mg/dL, usually >100mg/dL) is detected. In CSF Gram-staining, bacteria
and PMN-weighted leukocytes may be seen, and bacteria can be detected by CSF
culture or polymerase chain reaction (PCR) test. Cerebrospinal uid lactate (usually
>30mg/dL) and lactic dehydrogenase (LDH) levels (usually >20U/L) may be measured in ABM.Cerebrospinal uid lactate level may be helpful when CSF is bloody
or routine tests show unsatisfactory results [5].
Normally, leukocytes are not expected to be found in CSF.Generally, >5/mm3
leukocytes and >1/mm3 PMNs are considered abnormal. In cases where the CSF is
traumatized, the "corrected" CSF leukocytes are calculated. Accordingly, roughly 1
leukocyte/mm3 is subtracted for every 1000 red blood cells (RBCs)/mm3.
Cerebrospinal uid protein concentration in children with traumatic LP may be
increased due to increased protein concentration in plasma and protein secretion
from lysed erythrocytes. The “corrected” CSF protein concentration is roughly calculated by subtracting 1 mg/dL for every 1000/mm3 RBCs [5].
The use of oral antibiotics before the diagnosis of ABM may change the results
of CSF biochemistry, although it does not signicantly affect cytology [5].
Cerebrospinal uid culture positivity conrms the diagnosis. A CSF culture
should be obtained in all suspected cases of ABM.Cerebrospinal uid culture may
be positive without pleocytosis at the onset of infection [5].
Cerebrospinal uid culture may not be positive in children treated with antibiotics before LP, especially in meningococcal meningitis. In meningococcal meningitis, CSF rapidly becomes sterile after the parenteral administration of antibiotics. In
such cases, nucleic acid amplication tests or PCR-based molecular methods are
used to conrm the diagnosis of CNS infections [5]. Cerebrospinal uid cultures are
also negative in epidural or subdural abscesses [5].
A blood culture should also be obtained in a child with suspected meningitis.
Blood culture positivity strongly supports the diagnosis of ABM. Nasopharyngeal
or throat cultures do not help determine the etiology.
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31.6.2.3 Cerebrospinal Fluid Examination inNewborns
andPremature Babies
Some differences exist in CSF evaluation in newborns and preterm infants compared to older children. In general, the number of CSF cells is higher (usually up to
10/mm3), glucose levels are lower (may be as low as 30 mg/dL in term newborns,
20 mg/dL in premature newborns), protein levels are slightly higher (100 mg/dL in
term newborns, may be up to 120–160 mg/dL in premature babies). Cerebrospinal
uid leukocyte count >9/mm3 in infants <3 months and >6/mm3 in infants ≥3
months of age are generally considered abnormal. Therefore, the combined evaluation of ndings in newborns and premature babies becomes more important. The
cell count in neonatal gram-negative meningitis was generally higher than in group
B streptococcal meningitis [26, 27].
31.6.3 Cranial Imaging
Computed tomography or contrast-enhanced MR imaging in case of mental status
change (coma), papilledema, focal neurological decit (except sixth or seventh cranial nerve palsy), presence of CSF shunt, history of hydrocephalus, recent head
injury, or neurosurgery operation is recommended [5]. In addition, contrastenhanced cranial imaging is recommended in all neonatal meningitis, gram- negative
ABM, and all meningitis with a complicated clinical course. Magnetic resonance
imaging is advantageous because it does not contain radiation and shows soft tissues better. However, it can be counted among the disadvantages of being expensive, not being available everywhere, and requiring anesthesia in small babies and
children due to the extended shooting time.
Neuroimaging (transfontanellar cranial ultrasonography, CT, MR) is recommended routinely in newborn ABM because of a more complicated course compared to older infants and children. Cranial ultrasonography is the most commonly
performed examination, especially in the early stages of infection. It is benecial for
detecting intraventricular hemorrhage and measuring ventricular size. It can also
show ventriculitis, echogenicity, abnormal parenchyma, and extracerebral uid collections. It also provides bedside imaging in clinically unstable patients and allows
for follow-up. In the early period, CT and MR imaging may show cerebral edema,
ventricular obstruction, infarction, abscess, and subdural uid collections. Later in
treatment, contrast-enhanced MR imaging or CT helps detect cerebral abscesses,
areas of persistent cerebritis, infarction, or encephalomalacia, and the degree of
cerebral cortical and white matter atrophy. Contrast-enhanced neuroimaging should
be performed in all neonates with meningitis caused by organisms prone to intracranial abscess formation, including Citrobacter koseri, Serratia marcescens, Proteus
mirabilis, and Enterobacter sakazakii [28].
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31.7 Differential Diagnosis
Acute bacterial meningitis should be suspected if there are signs of meningeal
irritation on physical examination of a child who presents with fever, headache,
vomiting, and/or changes in consciousness. In addition, ABM should be considered in a child with any (serious) signs of infection accompanied by neurological
signs. The diagnosis of ABM is conrmed by CSF culture positivity, blood culture
positivity with CSF pleocytosis, and detection of bacteria in CSF by molecular
methods [5].
31.8 Treatment
Children with suspected ABM require prompt administration of appropriate antimicrobial therapy, immediate evaluation, and treatment (Table 31.1). Mortality in
untreated ABM is close to 100%. Even with optimal treatment, morbidity and mortality can occur, and neurological abnormalities are common among survivors [5].
31.8.1 General Principles
31.8.1.1 Supportive Measures
The basic supportive measures include appropriate respiratory support, venous
access for patients with hypoxia or respiratory distress, and appropriate hemodynamic support for children presenting with signs of shock. Supportive measures
include treating metabolic problems such as hypoglycemia, electrolyte abnormalities, and acidosis, and treating seizures if present [29].
Table 31.1 Commonly used antimicrobial agents for acute bacterial meningitis in children
Antimicrobial agents Doses
Penicillin G 300,000units/kg/day, IV, in 4 doses
Ampicillin 300–400mg/kg/day, IV, in 4–6 doses, max. 12g/day
Cefotaxime 225–300mg/kg/day, IV, in 3–4 doses, max. 12g/day
Ceftriaxone 100mg/kg/day, IV, in 2 doses, max. 4g/day
Ceftazidime 150mg/kg/day, IV, 3–4 doses, max. 6g/day
Cefepime 150mg/kg/day, IV, 3–4 doses, max. 6g/day
Gentamicin 5–7.5mg/kg/day, IV, in 3 doses
Meropenem 120mg/kg/day, IV, 3 doses, max. 6g/day
Aztreonam 120mg/kg/day, IV, 3–4 doses, max. 8g/day
Vancomycin 40–60mg/kg/day, IV, in 4 doses
Ciprooxacin 10mg/kg/dose, IV, 3 doses/day, max. 400mg/dose
Chloramphenicol 25mg/kg/dose, IV, 4 doses/day, max. 4g/day
Trimethoprim-sulfamethoxazole
(cotrimoxazole)
IV intravenous, max maximum
10–20mg/kg/day, IV, in 2–4 doses
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31.8.1.2 Fluid Management
Avoiding over- or under-hydration is an essential aspect of supportive therapy.
Fluid–electrolyte balance is vital for management. Hypotonic uids (e.g., 1/2–1/4
normal saline) should be avoided as they may increase the risks of hyponatremia
and cerebral edema. Optimal hydration should be maintained, considering the
patient’s volume status, hemodynamics, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH; e.g., serum sodium <130mEq/L). Children in
shock should be given adequate isotonic uids to maintain cerebral perfusion and
blood pressure. In case of hypovolemia without shock, daily weight, serum electrolytes, and urine output should be monitored and supplemented with isotonic uids.
In children with ABM, SIADH is common. For children without shock or hypovolemia and suspected SIADH, the uid restriction should be given to 2/3 to 3/4 normal saline maintenance. Daily weight, urine output, serum electrolytes, and serum
and urine osmolality should be monitored. Fluid administration can be normalized
when serum sodium is >135mEq/L.In a study of children with pneumococcal meningitis, 10% had serum sodium values <130 mEq/L at admission [29]. Children
without shock, hypovolemia, or signs of SIADH (normal perfusion, normal serum
sodium ≥135mEq/L) may receive isotonic uids as a maintenance uid. Volume
status and serum electrolytes should be monitored regularly, as SIADH may develop
during follow-up [29].
31.8.1.3 Follow-Up
Complications, such as seizures, IIP signs, and development of subdural effusion,
are most common in children treated for ABM during the rst 3 days of treatment.
Vital signs and a complete neurological examination should be monitored at regular
periods every day [29].
31.8.1.4 Hospital Infection Control
All patients with meningitis should be hospitalized in separate rooms, if possible,
and standard precautions for infection control should be taken. Droplet precautions
are recommended for N. meningitidis and Hib meningitis until the patients receive
effective 24-h therapy [29].
31.8.2 Antibiotic Treatment
Two basic principles should be considered in selecting antibacterial therapy for
ABM.The rst is that the antibiotic chosen should have a bactericidal effect, and
the second should have an excellent transition to CSF.Because the CSF is a region
of weaker humoral immunity, patients receiving bacteriostatic antibiotics (e.g.,
clindamycin or tetracycline) have a poor response to therapy [29]. For the treatment of ABM, a sufcient concentration of antibiotics should be present in the
CSF.Most drugs achieve only 10–20% of the peak concentrations of serum in the
CSF.Macromolecular antibiotics cannot adequately cross the BBB; small molecular weight and lipophilic molecules cross more easily. Inammation increases
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the permeability of the BBB, which facilitates the peak concentration of drugs in
the CSF.In a study of children with ABM, 2h after intravenous penicillin administration, the mean CSF/serum ratio was 42% on the rst day of treatment and
decreased to less than 10% on the 10th day when the inammatory ndings
regressed [29, 30].
31.8.2.1 Treatment Selection Based ontheBacteria
Neisseria meningitidis
Third-generation cephalosporins for meningococcal meningitis are preferred:
Ceftriaxone 100 mg/kg/day, maximum 4 g/day, in two equal doses, intravenous
(IV), or
Cefotaxime 225–300 mg/kg/day, maximum 12 g/day, in three or four equal doses, IV
High-dose penicillin G (300,000 units/kg/day, in four equal doses) is an alternative low-cost option. However, this treatment for non-beta-lactamase-producing
N. meningitidis isolates is preferred in cases with documented penicillin
susceptibility.
The course of treatment is 5–7days. Patients should receive antimicrobial therapy to eliminate nasopharyngeal carriage treated with penicillin [29].
Haemophilus influenzae
Third-generation cephalosporins for H. inuenzae meningitis are preferred:
Ceftriaxone 100 mg/kg/day, maximum 4 g/day, in two equal doses, IV, or
Cefotaxime 225–300 mg/kg/day, maximum 12 g/day, in three or four equal doses, IV
Ampicillin is used only in the presence of a non-beta-lactamase-producing
pathogen [29].
The course of treatment is 7–10days.
Gram-Negative Bacilli
The optimal treatment combination may vary depending on the growth pathogen
and antibiotic susceptibility/resistance characteristics. If possible, a pediatric infectious disease specialist consultation is recommended for children with gramnegative bacillus meningitis.
Enteric Gram-Negative Bacilli
As a treatment regimen for susceptible isolates, a broad-spectrum cephalosporin,
primarily ceftriaxone (100mg/kg/day, maximum 4g/day, in two equal doses, IV) or
cefotaxime (225–300mg/kg/day, maximum 12g/day, in three or four equal doses,
IV) plus an aminoglycoside (e.g., gentamicin 7.5mg/kg/day, in three equal doses,
IV) are preferred. Aminoglycoside may be discontinued, usually after the rst 5–7
days, once the CSF has been documented to be sterile [29].
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Pseudomonas aeruginosa
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In treating P. aeruginosa infections susceptible to ceftazidime (150 mg/kg/day,
maximum 6g/day, in three or four equal doses, IV) or cefepime (150mg/kg/day, in
three or four equal doses, IV) are effective cephalosporins. For P. aeruginosa iso-
lates resistant to ceftazidime, meropenem (120mg/kg/day, maximum dose 6g/day,
in three or four equal doses, IV) is an effective alternative.
Extended-Spectrum Beta-Lactamase (ESBL) Producing Organisms
Meropenem (120mg/kg/day, maximum dose 6g/day, in three or four equal doses,
IV) is the agent for treating meningitis caused by susceptible isolates [29].
31.8.2.2 Other Antibiotics
The role of tigecycline in the treatment of gram-negative bacterial meningitis is
limited because tigecycline CSF penetration is only 11% of serum levels, and CSF
concentrations after intravenous administration have been shown not to exceed the
minimum inhibitory concentration (MIC) of most Acinetobacter baumannii
strains [31].
Aztreonam has excellent CSF penetration through inamed and non-inamed
meninges. It crosses into CSF at 17–38% of serum levels sufcient for treating
meningitis [31].
Meropenem and imipenem penetrate CSF well. The use of imipenem is not the
primary choice in pediatric patients because it may cause seizures. A study showed
seizures developed in 33% of 21 pediatric cases using imipenem/cilastatin [31, 32].
Trimethoprim-sulfamethoxazole is well absorbed into the CSF; although it is not
a preferred agent, it can be added to the treatment when necessary.
Aminoglycosides cross the BBB poorly and usually do not reach sufcient concentrations in the CSF to kill pathogens causing meningitis when used parenterally.
Parenteral aminoglycosides are helpful only when given with another bactericidal
drug with good CSF penetration [31, 32]. Therefore, aminoglycosides are often
combined with a third-generation cephalosporin to treat gram-negative microorganisms. Although gentamicin is used more frequently, tobramycin or amikacin may be
used where they are susceptible. In the case of resistance to cephalosporins, aminoglycosides may be used intrathecally and intravenously simultaneously to treat
resistant gram-negative bacillary meningitis [31].
The concentration of ciprooxacin in the CSF of inamed and non-inamed
meninges was 8% and 37%, respectively [33]. In another study, ciprooxacin and
ooxacin reached 11–50% of their serum concentrations in CSF [34]. Moxioxacin
has been reported to achieve CSF concentrations of up to 80% of serum levels based
on data from patients with tuberculous meningitis [35]. Due to the lack of sufcient
clinical data, it should be used for treating multiresistant isolates. Physicians should
only use it with knowledge of its pharmacokinetics, dosage, and in vitro activity [36].
Like most third-generation cephalosporins, cefepime has adequate CSF penetration (5–20% of serum levels). Cefpirome passes into the CSF at 5–20% of its serum
concentration [31].
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