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CPG PDISP Acute Bacterial Meningitis
CPG PDISP Acute Bacterial Meningitis
PHILIPPINE
HILIPPINE CLINICAL PRACTICE GUIDELINES ON
Copyright 2015
A joint project of the Pediatric Infectious Disease Society of the Philippines (PIDSP) and
Child Neurology Society of the Philippines (CNSP)
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PIDSP and CNSP Bacterial Meningitis TWG, Acute Bacterial Meningitis CPG 2015
TABLE OF CONTENTS
Page
I. Introduction
A. History of the guideline 5
B. Target users of the guideline 5
C. Forming the guideline 5
D. PIDSP/CNSP Steering Committee 6
E. Criteria for Assessment of Strength of Evidence and Recommendation 6
II. Recommendations
A. Diagnosis of Acute Bacterial Meningitis
1. What are the signs and symptoms to suspect acute
bacterial meningitis? 7
2. What is the definitive test for bacterial meningitis? 8
3. How do we differentiate acute bacterial meningitis from
other CNS infections? 9
4. What are the contraindications to lumbar puncture? 9
5. What are the ancillary tests in the diagnosis of bacterial m
meningitis?
eningitis?
What is the value of each diagnostic test?
a. Complete blood od count (CBC) 10
b. Blood culture 11
c. C-reactive
reactive protein (CRP) 11
d. Polymerase chain reaction (PCR) 13
e. Latex Agglutination Test (LAT) 13
f. Procalcitonin 14
6. What is the role of imaging tests in the diagnosis of bacterial
meningitis? 15
B. Treatment of acute bacterial meningitis
7. What are the most common pathogens of acute bacterial
meningitis in the different age groups? 17
8. Are there signs and symptoms suggestive of a specific etiology? 21
9.What
What are the empiric antibiotics for acute bacterial meningitis?
a. Neonate (0-28 28 days old) 22
b. One month to 18 years old 23
10.What
What is the drug of choice for a specific et
etiologic agent?
a. Haemophilus influenzae 24
b. Streptococcus pneumoniae 24
c. Neisseria meningitidis 25
d. E. coli 25
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INTRODUCTION These
ese recommendations are intended for
Acute bacterial meningitis is defined as use by pediatricians, general practitioners
practi and
the inflammation of the meninges which is emergency medicine physicians to t serve as a
caused by bacteria such as Streptococcus guide in the management of bacterial
pneumoniae, Haemophilus influenza influenzae and meningitis.This
This guideline serves only as
Neisseria meningitidis. In developed countries, suggestions based on evidences collected that
the advent of vaccines for these organisms has would help lead each clinician to his/her rightful
significantly decreased the prevalence of decisions in the management of the patient.
bacterial meningitis1. For developing ccountries Key questions were formulated for the
like the Philippines however, uptake of the diagnosis (involving both clinical parameters
paramet
vaccines on a nationwide scale has yet to and laboratory procedures) and treatment
occur, thus a change in the epidemiology has protocols which include empiric and targeted
not been seen. From rom 2001 till 2010, meningitis therapy, as well as preventive measures by the
has always been in the top 10 leading causes PIDSP/CNSP Steering Committee.Committee The
of mortality in children2. Based on the committee searched for both local and
Philippine Pediatric Society disease registry, international researches pertaining to the
out of the 934,633 cases reported from diagnosis, treatment and prevention of acute
January 1, 2006 to August 31, 2010, there bacterial meningitis. Workshops were also
were 5,611 cases of unspecified meningitismeningitis. organized for the critical appraisal of the
Resistance
esistance rates of pathogens to evidence and were graded using the WHO
antimicrobials have not decline declined. The criteria for strength of evidence.
ev
emergence of new resistance for antibiotics Recommendations were made based on the
have been reported. In n 2012, all S. literature obtained, local data, and expert
pneumoniae isolated were ere sensitive to opinion of committee members. The guideline
levofloxacin. However,
owever, in the 2013 has been presented to the CNSP and PIDSP.
Antimicrobial Resistance Surveillance Program It also has been presented at the Philippine
(ARSP), 2% resistance to levofloxacin (95% Pediatric Society
ociety Annual Convention
C as well as
CI: 0.5-5.8) was reported.4 With varying clinical the PIDSP annual convention. The therapeutic
presentations and rising rates of bacterial guidelines has also beeneen discussed with the
resistance, the appropriate management of this with the National Antibiotic Guideline
disease from its recognition to therapy remains Committee of the Department of Health,
of paramount concern. Thus to address these Philippines.The
The feedback generated were
changes,
ges, this guideline was developed. taken into consideration and incorporated
incorp in
The first guideline for acute bacterial the guideline where appropriate.
appropriate
meningitis was completed in 1998 as
commissioned by the Philippine Society for
Microbiology and Infectious Diseases (PSMID),
however, the guideline was not published. The Disclaimer: Brand names of certain products
Pediatric
atric Infectious Disease Society of the may appear within the text, however, we are
Philippines (PIDSP), in line with its 20th not in any way promoting or encouraging its
anniversary celebration in 2013, saw the need use. They appear in this guideline for
for an update and publication of this guidelin
guideline, information purposes only.
thus, it formed a committee in partnership with
Child Neurology Society of the Philippines
(CNSP) to develop these current
recommendations.
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PIDSP and CNSP Bacterial Meningitis TWG, Acute Bacterial Meningitis CPG 2015
Therefore, in cases where the signs and cells per mm3 and/or more than 80%
symptoms lead to a suspicion of bacterial polymorphonuclear cells) had a lumbar
meningitis, further work up such as a lumbar puncture done prior to antibiotic therapy16. In
puncture is definitely warranted unless there this group of patients, 85% of them had the
are contraindications to the procedure. diagnosis confirmed by a positive CSF culture
result. Specifically, 96% of these patients were
2. What is the Definitive Test for Bacterial positive for Haemophilus influenza,
influenza 87% for
Meningitis? pneumococcal meningitis and 80% for
Cerebrospinal fluid (CSF) culture is the gold meningococcall meningitis. Post treatment
standard for the diagnosis of acute bacterial cultures were not recommended. Yield of
sample substantially decreases if CSF cultures
meningitis.
were done in patients with prior antibiotic
[Level of evidence: High; treatment16.
Strength of Recommendation: Strong] Despite technological advances such as
PCR and latex agglutination to aid in the
diagnosis of meningitis, CSF culture still
In a retrospective study, 875 patients remains as the definitive test for acute bacterial
diagnosed with meningitis (defined in the study meningitis.
as CSF white blood cell count of over 1,000
Table 3.. CSF cellular parameters in normal individuals and in patients with different types of
meningitis.
Leukocytes/µL Pressure Protein Glucose Others
(mmH20) (mg/dL) (mg/dL)
Normal term 0-20 10-14 <1.0 >0.6 (or >2.5
2.5
neonate mmol/L)
Normal 0-5 90-180 <0.4 45-80
(>1 month)
Bacterial 100-10,000; Usually 100-500, <0.4 Organism seen on
meningitis PMN elevated; occasional (may be normal) smear or
predominance 200-300 ly >1000 recovered on
culture
Viral 10-3000; 90-200 50-100 Usually normal;
normal No organisms
meningitis initially PMNs, slightly reduces seen on stain or
then in mumps recovered on
lymphocyte meningitis and culture
predominate LCM
TB meningitis 25-100; 180-300 100-200, Usually Acid fast
Lymphocyte may reduced; <40 0 organisms may be
predominance; >1000 if seen
in early stages block is
PMN present
Cryptococcal 10-200, 180-300 50-200 Reduced,, <40 Positive India ink
meningitis lymphocytes
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contraindicated27. Population in the sstudy was due to the presence of contraindications, the
composed of patients with suspected bacterial patient should be started on antibiotic therapy
meningitis aged 1 month and older. Results immediately after collection of sample for blood
have shown that peripheral morphonuclear culture22.
(PMN) leukocyte counts of >16 x 109/L, serum In local practice, blood culture is routinely
CRP level of >100 mg/L, and hemorrhagic requested as part of the laboratory work up in
rash were highly associated with bacterial febrile children. Not only is blood culture a
meningitis or meningococcal disease. If any diagnostic tool, it also serves as a guide in
one of these factors were present in the antimicrobial therapy. The drawbacks are that
patient, the probability for the presence of blood culture is expensive
pensive and it is not always
bacterial meningitis rose to more than 95% available especially in remote areas, and the
and even higher to >99% if there were 2 or results could take 2-7
7 days before its release.
more of these variables present27.
On the other hand, h white blood cell c. C-Reactive
Reactive Protein (CRP)
counts are frequently requested, these
parameters are of no value in ruling out a Serum and CSF CRP are useful in confirming
serious infection. In n a systematic review
and excluding bacterial meningitis.
performed to determine the value of laboratory
tests in the diagnosis of serious infections in [Level of evidence: High
febrile children, results have shown that the Strength of Recommendation: Strong]
white blood cell count assays have a negativ
negative
likelihood ratio of 0.61 to 1.1428. These white
blood cell indicators were shown to have more
merit in ruling in a serious infection (positive C-reactive protein is an acute phase
likelihood ratio (LR) from 0.87 to 2.43). reactant used in the diagnosis and in
However, compared to inflammatory markers monitoring the course of infection29. It
such as CRP or procalcitoni procalcitonin, the increases in most microbial infections, making
inflammatory markers showed more value in it a reliable and sensitive marker for
ruling in the diagnosis of a serious infection28. infection30,31. In normal children, serum CRP
levels are very low and it quickly rises within 12
b. Blood Culture to 24 hours in the presence of infection32.
In a meta-analysis
analysis of 5 studies of 1379
In patients suspected to have bacterial children, serum CRP was found to have a
meningitis, blood culture should be pooled positive likelihood ratio of 3.15 (95%
( CI
performed prior to starting antibiotic 2.67-3.71)
3.71) and a pooled negative likelihood
therapy. ratio of 0.33 (95% CI 0.22-0.49)
0.22 for serious
infection28. In cases of serious infection
[Level of evidence: Moderate; wherein CSF findings are consistent with
Strength of Recommendation: Strong] meningitis, but the Gram stain turned out
negative and antimicrobial therapy is still being
considered to be given or not, then serum CRP
levels may be of help in decision making since
Suspicion of bacterial meningitis warrants a serum CRP level has a high negative neg
lumbar puncture and blood culture to correlate predictive value if it turns out to be normal17.
the CSF findings with the clinical picture17. In The serum CRP or CSF CRP can be
instances where lumbar puncture is defedeferred helpful in the diagnosis of bacterial meningitis
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especially for cases where there is difficulty in following results for CSF CRP in pyogenic
isolating organisms32. In fact, CSF CRP can be 100 32,36; Sn
meningitis: Sn 84% and 94%, Sp 100%
useful in the diagnosis of partiallypartially-treated 97% and Sp 98% ; Sn 97% and Sp 86%38.
37
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PIDSP and CNSP Bacterial Meningitis TWG, Acute Bacterial Meningitis CPG 2015
the start of treatment (p<0.05)45. Thus serum Determination of serum procalcitonin level
procalcitonin may be used in monitoring is a good diagnostic test which helps
response to antimicrobial therapy in bacterial differentiate
e bacterial from viral infections. In
meningitis especially in cases where a repeat the country, the test is relatively new and
lumbar tap is not possible. available in only a few institutions, plus it is
Results obtained by Taskin et al al. (2004) quite expensive.
were consistent with the results described
above47. Forty four children were ere diagnosed 6. What is the role of imaging tests in the
with meningitis (22 bacterial, 22 viral) based on diagnosis of bacterial meningitis?
clinical presentation, CSF parameters, and
Gram stain and culture. Blood were extracted Neuroimaging is used to o identify the presence
from patients at the time of diagnosis and at of complications of bacterial meningitis and to
48-72
72 hours after initiation of treatment. rule out contraindications in doing a lumbar
Results showed that the serum procalcitonin tap.. Neuroimaging is not used to diagnose
level at the time of diagnosis for patients with the presence or absence of a CNS infection.
bacterial meningitis was 75.8+29.8 29.8 ng/L
compared to the control group of 0.3 0.3+0.2 ng/L [Level of evidence: Moderate
Strength of Recommendation: Strong]]
Strong
(p<0.001). Serum procalcitonin levels were
significantly higher as well at 48-7272 hours after Neuroimaging in acute bacterial meningitis
onset of treatment in patients with bacterial is primarily used to rule out structural lesions
l
meningitis (35.7+19.6
19.6 ng/L) compared to levels and cerebral herniation and also to detect and
in patients with viral meningitis (0.3
(0.3+0.1 ng/L) monitor complications of meningitis. For
(p<0.001). These findings were similar as well uncomplicated cases of meningitis wherein
by the results obtained from a meta meta-analysis there is no doubt on the diagnosis, imaging is
on studies on serum procalcitonin
rocalcitonin and CRP not required. Any sign or symptom that
levels as markers of bacterial infection. Serum suggests an increased intracranial pressure
procalcitonin markers were found to be better dictates a cranial CT or MRI be done prior to
than CRP markers in distinguishing bacterial lumbar puncture.
from viral infections, with procalcitonin having a The cranial imaging in bacterial meningitis
positive Likelihood Ratio of 6.05 ((95% CI: may show pial ial enhancement with occasional
4.67–7.82) and negative Likelihood
ikelihood Ratio of brain swelling or minimal widening of extra-extra
49
0.10 (95% CI, 0.06–0.15). ). CRP markers on the axial CSF spaces . For uncomplicated cases,
other hand had a positive Likelihood
ikelihood Ratio of imaging is normal in most cases24. However,
3.75 (95% CI: 3.06–4.59)) and a negative for patients that are not clinically improving or
Likelihood Ratio of 0.20 (95% CI: 0.150.15-0.27)48. those with new onset neurological signs or
Furthermore, procalcitonin was shown to be symptoms despite therapy, neuroimaging is
superior to CRP in terms of distinguishing advised50.
between bacterial infections from non non- Based on the four year-surveillance
year review
infectious inflammatory conditions. The (July 2011-November
November 2014) on the clinical
difference was statistically significant (p<0.05) practice guideline on bacterial
acterial meningitis and
in terms of the test’s sensitivity (88%, 95% CI: meningococcal septicemia of the National
80-93% for procalcitonin;
onin; 75% (95% CI: 62% 62%– Institute for Health and Care Excellence, MRI
84%) for CRP markers) as well as in its has no role in the diagnosis of bacterial
specificity (81%, 95% CI: 67% 67%–90% for meningitis50. This was based on a systematic
procalcitonin; 67%, 95% CI: 56%–77% 77% for CRP review of 5 studies which showed that MRI has
markers)48. low sensitivity in diagnosing bacterial
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Table 5. Summary of pathogens isolated in neonates and extended neonates obtained from data
from local and international researches.
Table 5A. Local Researches
(REF)Author and Description Pathogens isolated
(57)Maramba et al, 2011; Multicenter surveillance Gram negative bacteria (94%): Pseudomonas
and chart review (July-Dec
Dec 2006), <28 days old spp., Burkholderia spp.,, and Klebsiella spp.
(58)Ignacio et al, 2012; Retrospective, descriptive Enterobacter aerogenes (55%),
(55%) Acinetobacter
(July 2004 to June 2006) baumanii and coagulase negative
Staphyloccoccus
(59)Quiambao et al, 2007; Prospective (April H. influenzae, S. typhi, Salmonella group, E.
1994- May 2000), infants <60 days old coli, Pseudomonas, Klebsiella sp.,
sp. and
Enterobacter sp.
(60)Morelos and Gatchalian, 1996; Gram negative bacteria (69%): E. coli,
coli K.
Retrospective, descriptive (July 1982
1982-Dec 1994) pneumoniae, Salmonella sp.,
sp. P.aeruginosa,
Acinetobacter,, E. cloacae,
Group B Strep (9.3%)
(34)Sutinen et al, 1999; Retrospective, descriptive 3 isolates (S.
S. pneumoniae)
pneumoniae and 1 isolate E. coli
(Oct 1983 to Nov 1984), Manila, 0--2 months old
Table 6. Summary of pathogens isolated in infants and children obtained from data from local and
international researches
Table 6A. Local researches
(REF)Author and Description Pathogens isolated
(70)Galagar et al, (Jan 2010-DecDec 2014) >2 mos
mos-18 H. influenzae type B (44%), S. pneumoniae
yrs (24%)
(69)Espino et al, (2009-2011)
2011) Jap B enceph (34%), Dengue (9.3%), H,
2mos-18yrs,
18yrs, 5 sentinel sites in Luzon and Visayas influenzae type B (10%), S. pneumoniae
(9.3%), N.. meningitidis (1.5%)
(66)Abucejo-Ledesma
Ledesma et al, 2007; Prospective H. influenzae type B (37%) and S. pneumoniae
(April-May 2000), Bohol, 0-59
59 mos (18%)
(67)Tam et al, 2001; Retrospective (1994
(1994-1999), H. influenzae and S. pneumoniae most
PCMC common
(34)Sutinen et al, 1999; Retrospective 5 H. influenzae type B,, 3 N. meningitidis, and 4
(Oct 1983-Nov
Nov 1984), Manila, 3 mo
mo- 15 yrs S. pneumoniae
(68)Abucejo et al, 2000; (Jan 1995--Dec 1998), <5 H. influenzae type B (43%) and S. pneumoniae
yrs old (16%)
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A local study in Bohol on children with from other countries. Confirmed cases
bacterial meningitis
gitis revealed that for children attributed to S. pneumoniae (56.67%), H.
0-59 months old, H. influenzae type B (37%) influenzae type B (10%),
(10%) and N. meningitidis
and S. pneumoniae (18%) were very (6.67%) were isolated in children 3 months old
common66. H. influenzae was the most to 18 years old in a retrospective study of
common organism observed while S. hospitalized children in Western Uttar
pneumoniae, Pseudomonas, Salmonella and Pradesh71. Similar isolates were obtained as
E. coli were less frequently seen in the CSF well in a study in Yemen from 1999-2001
1999 on
culture in a retrospective study of 90 patients at children 1 month to 15 years old with clinical
Philippine Children’s Medical Center (PCMC) features of acute bacterial meningitis72. There
from 1994 to 199967. The same pathogens were 153 cases with positive cultures of S.
were isolated in 3-month
month old to 15 year old pneumoniae (30.1%), H. influenzae (15%), N.
children with CNS infection in Manila (out of 15 meningitidis (52.9%) plus S. aureus (1.3%) and
bacterial isolates
es within this age group, there E. coli (0.7%). In Vietnam, a prospective study
were five H. influenzae type B,, three N. revealed that in children younger than 15 years
pneumoniae)34. H.
meningitidis, and four S. pneumoniae old with bacteriall meningitis, the most common
influenzae type B (43%) and S. pneumoniae bacteria seen were H. influenzae type B (26%)
(16%) were also the common microorganisms and S. pneumoniae (25%)73. This was also
identified in a study in children less than 5 observed in a prospective multicenter
years old with bacterial meningitis in a observational study in Cameroon involving 170
provincial hospital in the Philippines, the data children aged 2 months to 15 years, with
were collected from 1995 to 199868. In a bacterial meningitis.
ngitis. The CSF PCR was
multicenter study with sites in Luzon and the positive in 112 children (64 were positive for S.
Visayas, patients with th symptoms of CNS pneumoniae,, 31 were positive for H. influenzae
infection had H. influenzae type B and S. type B and 17 were positive for N.
pneumoniae as the most common bacterial meningitidis)74. The pneumococcal and Hib
pathogens, although viral etiologies (Japanese meningitis were frequently seen in children
encephalitis and Dengue) were found to be aged 9 to 15 months onths while meningococcal
more common69. meningitis were found more often in 72-month
72
A recent study at the Philippine General old children. Furthermore, in Mozambique, a
Hospital included 68 patients aged 2 months to study including patients more than a month old
5 years with bacterial
acterial meningitis from 2010
2010- showed similar microbiological isolates as
70
2014 . Only 36% had an identified pathogen in well75. There were 330 CSF samples but only
the CSF. The dominant bacteria were H. 46 had a positive culture result out of which
influenzae B (44%) and S. pneumoniae (24%). 6.5% grew H. influenzae type B, B 26% N.
In the same study, there was only 1 positive meningitidis,, and 6.5% grew S. pneumoniae in
isolate in a patient more than 5 yrs which was patients aged 1 year to 20 years. More studies
identified
tified as S. pneumoniae. The dominance of from different countries are listed in Table 6B
these pathogens is not surprising since the Hib which shows the etiology of bacterial
and pneumococcal conjugate vaccines were meningitis in patients 2 months
mo and older.
only included in the National Expanded
Program for Immunization in 2013 and has not
been implemented nationwide.
The type e of microorganisms obtained from
CSF cultures was consistent even with studies
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8. Are there signs and symptoms and abnormal skin color were noted to be
suggestive of a specific etiology? important features of meningococcal disease
There are no signs and symptoms and signify early sign of the disease (occurs
suggestive of a specific etiology except for within 12 hours of onset of illness) in children
meningococcal meningitis. Classic and adolescents89. These were observed in the
symptoms include a hemorrhagic rash, review of data ata gathered from parents of
impaired consciousness and meningism. children 0-16 16 years old who died from
[Level of evidence: High meningococcal disease from 1997-1999
1997 in
Strength
rength of Recommendation: Strong] England, Wales and Northern Ireland.
A retrospective study compar compared the Symptoms of meningism, rash and impaired
clinical profile of 300 pediatric patients with consciousness were said to occur later in the
meningitis secondary to H. influenzae and S. course of illness.
pneumoniae infections86. Nuchal uchal rigidity as
well as prolonged fever were associated with 9. What are the empiric antibiotics for acute
H. influenzae meningitis (p=0.05), whereas a bacterial meningitis?
bulging fontanel and frequent seizures were a. in neonates? (0-28
28 days old)
more likely to be found in patients with For neonates with acute bacterial meningitis,
pneumococcal meningitis. However, in a study the recommended empiric therapy is the
by Panlilio and Lee e from 1984 to 1989 in combination of an
pediatric patients with bacterial meningitis at Ampicillin* OR Cefotaxime
efotaxime* OR Ceftriaxone*
PCMC, there was no significant difference PLUS
found between patients with H. influenzae or an aminoglycoside*.
aminoglycoside
pneumococcal meningitis in terms of the *depending on the local resistance pattern
clinical picture of those patients who developed [Level of evidence: Moderate
subdural effusion87. The only difference Strength of Recommendation: Strong]
observed was that those with H. influenzae
infection had a more prolonged clinical course
course.
Since children with bacterial meningitis usually In developed countries, the recommended
have non-specific
specific signs and symptoms (fever, empiric therapy includes an ampicillin plus
vomiting, irritability, headaches, musc
muscle pain or cefotaxime OR an ampicillin plus an
joint pains) that may be indistinguishable to aminoglycoside.
inoglycoside. This was based on the fact
other illnesses, signs and symptoms alone are that most of the organisms affecting neonates
not sufficient as basis for diagnosis of the were Group B Streptococci,
Streptococci Escherichia coli,
disease. Listeria monocytogenes,
monocytogenes Gram negative
In the case of meningococcal
ngococcal disease, enterics and S. pneumoniae90,91,92,93,94,95.
some children may present with more specific However, in developing countries such as
signs and symptoms such as rash and altered the Philippines, the isolated organisms differ
mental status which may become more severe from those in developed countries because of
and specific over time23. A local retrospective multiple factors such as population
study in Baguio city described the profile of 217 characteristics, genetics and the individual’s
patients infected with Neisseria meningitides
meningitides. immune response, and techniques in the
One hundred of these patients comprised of laboratory including pathogen
pat isolation and
96,97
children from 0-18 18 years of age. All of the reporting , not to mention varying microbial
patients had a history of fever; majority of them resistance patterns as well.
(90%) had rashes, 39% of which was purpuric Bacterial pathogens causing meningitis can
in character88. Leg pain, coldold hands and feet also cause sepsis as well. A multicenter
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surveillance and chart review of neonates might have significantly affected the outcomes
diagnosed with sepsis in five ve hospitals in the of the study.
Philippines has shown that the predominant The empiric treatment of neonatal
organism isolated in cultures was Gram meningitis must be adjusted accordingly based
negative bacteria (94%) (Pseudomonas
Pseudomonas spp., on onset
nset of disease, local epidemiology,
Burkholderia sp., Klebsiella spp.).). No Group B bacterial resistance patterns and available
57
Streptococci were seen . Four out of the five resources42. Currently, Group B Streptococci is
hospitals used the e combination of ampicillin not common. As for resistance patterns, if
and aminoglycoside (amikacin or gentamicin) bacterial resistance of Gram negative bacilli to
as first line therapy for neonatal meningitis, ampicillin is high, a third generationgenerat
however, in about half of these patients, the cephalosporin PLUS an aminoglycoside may
antibiotics were shifted due to either be given. If the resistance is low, ampicillin
inadequate response to therapy or because the PLUS an aminoglycoside would suffice. Also,
resultss of culture and antibiotic susceptibility consider the price of medications. The
testing showed a different but more appropriate ampicillin plus an aminoglycoside is less
drug to use. expensive than a third generation
With regard to early onset and late onset cephalosporin
losporin plus an aminoglycoside.
sepsis, no particular antibiotic regimen can be Ceftriaxone is contraindicated in neonates
recommended as of this time. For early who are hyperbilirubinemic, particularly in
neonatal sepsis, a review of two randomized, premature babies99. Ceftriaxone can displace
controlled trials
rials comparing monotherapy to bilirubin from serum albumin thus aggravating
combination therapy has shown to have no the condition which in turn may lead to
significant difference in mortality, treatment kernicterus. Ceftriaxone is also contra-
contra
failure or bacteria resistance. According to the indicated in neonates who are less than 28
reviewers, there is not enough evidence to days of age who are receiving treatment with
support any particular antibiotic regimen ove over containing intravenous solutions99.
Calcium-containing
another, thus more studies regarding this This is due to the risk of precipitation of the
matter are needed98. The same goes for late Ceftriaxone-calcium
calcium salt and deaths
deat have been
onset neonatal sepsis as there is still lacking reported due to this. When Ceftriaxone is
evidence to justify treatment protocols. In the contraindicated in the neonate, Cefotaxime
review by Gordon and Jeffrey (2005), although should be used.
there were thirteen studiess identified for
inclusion in the review, in the end, only one b. 1month to 18 years old
small study on 24 neonates was reviewed
because majority of these studies did not
differentiate data for early and late onset For children 1 month--18 years old with
sepsis98. The study compared beta beta-lactam acute bacterial meningitis, the
monotherapy with the combination of beta- recommended empiric therapy is
lactam plus an aminoglycoside and there was Ceftriaxone OR Chloramphenicol
hloramphenicol.
no significant difference noted for mortality [Level of evidence: Moderate
(relative risk 0.17, 95% CI 0.01 0.01-3.23) or Strength of Recommendation: Strong]
Strong
treatment failure (relative risk 0.17, 95% CI
0.01 to 3.23). There were no documented Empiric antibiotic therapy must take into
cases of antibiotic resistance in either group. consideration the antibiotic resistance pattern
However, it is important to note that since the of thee locality. In the Philippines, S.
study was small, the small population size pneumoniae does not show the same
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Based on the above data, ata, patients on Although there is no difference between
ampicillin had poor responses in spite being cephalosporin and conventional antibiotics in
sensitive in the time period stated. Patients the clinical outcome, ceftriaxone provides an
treated with chloramphenicol and 3rd advantage over chloramphenicol because of
generation cephalosporins had higher cure lower culture positivity after 10-48
10 hours, lower
rates, thus these are still being recommended levels of resistance and twice daily dosing of
at the moment. ceftriaxone compared to the 4 times daily
injection of chloramphenicol.
chloramphenicol
10. What is the drug of choice for a specific
etiologic agent? b. Streptococcus pneumoniae
a. Haemophilus influenzae
The drug of choice for Streptococcus
The drug of choice for Haemophilus pneumoniae meningitis is penicillin for 10-
influenzae meningitis is Ceftriaxone for 7
7- 14 days.. Alternative agents are
10 days.. Alternative treatment would be chloramphenicol and ceftriaxone.
chloramphenicol. [Level of evidence: Moderate
[Level of evidence: Moderate Strength of Recommendation: Strong]
Strength of Recommendation: Strong
Strong]
According to the Practice Guidelines for the
In developed countries, the antibiotic of Management of Bacterial Meningitis by the
choice for beta-lactamase
lactamase negative H. Infectious Diseases Society of America,
America the
influenzae is ampicillin, alternatively, recommended treatment of meningitis caused
ceftriaxone, cefotaxime, cefepime, by penicillin sensitive-S.
S. pneumoniae based on
chloramphenicol or fluoroquinolone may be microbial susceptibility is either
ei a penicillin,
used. For beta-lactamase ctamase positive H. third generation cephalosporin or a
influenzae,, drug of choice is a third generation vancomycin plus third generation
cephalosporin. Cefepime, chloramphenicol, or cephalosporin combination17. If the penicillin
fluoroquinolone may be used as alternatives17. minimum inhibitory concentration (MIC) is <0.1
On the other hand, for Haemophilus influenzae ug/mL, penicillin G or ampicillin is
type B (Hib)) meningitis, the recommended recommended.
initial antibiotic treatment is either a ceftriaxone Based on the ARSP 2014, the penicillin
or cefotaxime with alternatives such as the resistance rate for Streptococcus pneumoniae
combination of chloramphenicol/ampicillin or isolates was 7% % based on meningeal
chloramphenicol/amoxicillin for 7 to 14 days22. 100
breakpoints . There was no report of
In the NICE guidelines of 2010, for children at resistance to ceftriaxone. Invasive isolates
least 3 months old, ceftriaxone axone IV for is obtained were subjected to susceptibility
recommended for H. influenzae type B testing with ceftriaxone and cefotaxime using
meningitis23. Local surveillance data shows meningitis and non-meningitis
meningitis breakpoints at
that for H. influenzae type B, the resistance for the reference laboratory. Resistance of S.
ampicillin, chloramphenicol and cotrimoxazole pneumoniae to chloramphenicol was 4%. Our
were 12%, 13.4% and 42.9% respectively. All local antibiotic sensitivity pattern is very
the ampicillin isolates were β lactamase different from other developed countries. In the
positive100. But for CSF Hib isolates, resistance United States (2013) data shows that
rates were 25%, 0% and 60% respectively for pneumococcal bacteria are resistant to one or
the previously mentioned antibiotics. more antibiotics in 30% of cases105.This is the
reasons for different recommendations for
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empiric and definitive therapy for bacterial in their patients.. In 2013, local resistance rates
meningitis in different countries. did not have any resistance to penicillin,
Ceftriaxone or chloramphenicol (personal
c. Neisseria meningitidis communication with Dr. Celia Carlos, Head
ARSP) The he resistance rate for Neisseria
Penicillin is the drug of choice for
meningitidis was not included
ncluded in the 2014
Neisseria meningitidis meningitis for 7
ARSP data.
days. Alternative agents are ampicillin,
d. Escherichia coli
ceftriaxone, chloramphenicol, and
cefotaxime. For E. coli, cefotaxime is the specific
[Level of evidence: Strong treatment to be given for at least 21 days.
Strength of Recommendation:: Strong
Strong: Ceftriaxone may be used as an alternative
Strong]
to cefotaxime but it is contraindicated for
According to the NICE guideline for
use in premature babies or in babies with
bacterial meningitis and meningococcal
jaundice, hypoalbuminemia or acidosis as it
septicemia in children (2010), treatment for
may exacerbate hyperbilirubinemia.
hyperbil
children with confirmed meningococcal disease
Treatment needs to be individualized on the
or clinically suspected meningococcal disease
basis of patient’s clinical response.
is intravenous ceftriaxone for 7 days23. In the [Level of evidence: Moderate; Strength of
IDSA guideline, N. meningitides isolates w with a Recommendation: Strong]
MIC of <0.1 ug/mL, penicillin G or ampicillin is
recommended
mended (alternative: ceftriaxone, According to the NICE guidelines, infants
cefotaxime, chloramphenicol). If MIC is less than three months of age with meningitis
between 0.1-1.0 1.0 ug/mL, ceftriaxone or caused by Gram negative bacilli are
cefotaxime is advised (alternative: recommended to be given intravenous
chloramphenicol, fluoroquinolone, cefotaxime for at least 21 days until antibiotic
meropenem)17. The EFNS guideline on the sensitivity results come out with a more
management of community acquired b bacterial specific drug23. For complicated cases such as
meningitis (2008) has a similar presence of effusion or abscess, poor
recommendation: benzyl penicillin or response to antimicrobial therapy and
ceftriaxone or cefotaxime (alternative: concurrent intraventricular hemorrhage in
meropenem or chloramphenicol or premature infants, extending the duration of
22
moxifloxacin) for 5 to 7 days . treatment as well as consultation with an
A local retrospective, descriptive study was infectious disease specialist is advised. The
done in Baguio city involvingolving patients with a EFNS guideline on management of community
discharge diagnosis of either meningo meningo- acquired bacterial meningitis has
coccemia, meningococcal meningitis or recommended either ceftriaxone, cefotaxime or
meningococcal disease in a tertiary meropenem for Gram negative Entero- Entero
88
government hospital from 2004-2006 2006 . Out of bacteriaceae in general. There was no specific
the 217 patients, 51% was diagnosed with drug mentioned for E. coli22. Third generation
meningococcemia and 46.08% was comp composed cephalosporin was also the recommended
of children 18 years old and below, and this treatment for E. coli meningitis by the
event was considered by the WHO as an Infectious Disease Society of America
outbreak. The pathogen isolated was Neisseria guideline for the management of bacterial
meningitidis Serogroup A subtype A1.9. During meningitis17. Alternatives include aztreonam,
aztreonam
the outbreak, N. meningitidis remained to be fluoroquinolone,, meropenem, trimethoprim-
trimethoprim
sensitive to penicillin, and had d good outcomes sulfamethoxazole and ampicillin.
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unspecified bacterial meningitis was also 13. Is it appropriate to step down to oral
mentioned in the European Federation of therapy?
Neurological Societies guideline22.
Empiric antimicrobial treatment of 10 10-14 1. Switching from intravenous to oral
days will most likely benefit patients. Until more antibiotic therapy for bacterial meningitis is
supporting evidence becomes available, generally not recommended due poor
empiric
ic therapy is recommended to be given penetration of most oral antibiotics
anti into the
intravenously to achieve optimal concentration CSF.
of the antimicrobial drug in the CSF. 2. Chloramphenicol is the only antibiotic
which could be used orally for treating
12. What are the indications to shift to community acquired CNS infections. If
another antibiotic agent? necessary, IV chloram-phenicol
chloram can be
switched to oral form after 3 to 4 days of
Modification of the antimicrobial regimen initial therapy in children > 3 months old
should be made after er careful assessment and are well nourished.
of both clinical and microbiological 3. Antibiotic resistance patterns should be
parameters which include but not limited to considered when chloramphenicol is used
the following: due to reports of resistant strains of H.
1. Absence of or limited improvement influenzae.
despite adequate antibiotic coverage (e.g. 4. Drug interactions should be monitored
persistent fever after 36-48 48 hours of when there is concomitant use of
adequate antibiotics); chloramphenicol and phenobarbital or
2. Clinical deterioration phenytoin.
3. Drug intolerance [Level of evidence: Moderate; Strength of
4. Resistant isolate based on cultures and Recommendation: Strong]
clinically compatible with the clinical
course. There is currently very limited evidence to
Level of Evidence: Moderate support the use of oral antibiotics for the
Strength of Recommendation: Strong treatment of bacterial meningitis. Most of the
antibiotics used intravenously have oral
With appropriate antimicrobial therapy, equivalents which have poor penetration into
microbiologic evidence of CSF sterilization the CSF. The studies available on oral
occurs within 48 hours of treatment. Currently, antibiotics for meningitis involve
there is no hard and fast rule that governs this chloramphenicol. The oral form of
topic since there are no randomized controlled chloramphenicol has good bioavailability and
trials or prospective trials
rials available that serves CNS penetration. Based on a pharmacokinetic
as evidence to address this issue. The study on the use of oral and intramuscular
recommendations as stated above are solely chloramphenicol on Filipino children less than
based on clinical experience and expert 3 months old, chloramphenicol was found to
opinion. The decision to shift antibiotics rests have an unpredictable metabolism108. Oral
on the physician’s clinical judgment
judgment, as chloramphenicol is should not be given in
supported by microbiological
robiological evidence when infants below 3 months old as well as in
available. malnourished children because the drug has
an unpredictable absorption and may
accumulate to toxic levels. The injectable form
is preferred. For bacterial meningitis, the
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sequelae in children from high income According to the NICE clinical guideline
countries (risk ratio 0.67, 95% CI 0.46 to 0.97) for bacterial meningitis and meningococcal
but no long term decrease in neurological septicemia in children23, dexamethasone (0.15
sequelae was observed (risk ratio 0.90, 95% CI mg/kg, maximum dose of 10 mg, every 6 hours hou
0.74 to 1.10). for 4 days) should be given as soon as
As for mortality, giving corticosteroids in possible to patients with either suspected or
patients with S. pneumoniae meningitis confirmed bacterial meningitis if the lumbar
significantly reduced mortality (risk ratio 0.84, puncture shows any of the following laboratory
95% CI 0.72 to 0.98), the case is different with results: purulent CSF, CSF WBC count
N. meningitidis meningitis since no significant >1000/microliter, increased CSF WBC count cou
reduction in mortality was observed (risk ratio with CSF protein > 1 g/liter, and presence of
0.71, 95% CI 0.35 to 1.46). In addition, bacteria in Gram stain. However, children
corticosteroids had no effect on mortality for below 3 months of age with suspected or
patients with H. influenzae meningitis112. confirmed bacterial meningitis should not be
Corticosteroids had no significant effect for given corticosteroids. If there is an indication to
children in low income countries. give dexamethasone but it was wa not given
In the systematic review by Furyk et al., together with or prior to the first dose of
(2011) on neonatal meningitis in the antibiotics, give the first dose of
developing world, steroids were mentioned as dexamethasone within 4 hours of starting the
adjunctive therapy9. There were two non non- antibiotic. However, defer administration of
randomized studies which suggested some dexamethasone if antibiotics were given for
benefit by steroid therapy. However, there was more than 12 hours already.
one note of a small randomized controlled trial The NICE center for clinical practice-
practice
in Jordan with a small sample size of 52 which surveillance program made a 4-year
4
showed no significant difference in morbidity or surveillance review of the 2010 guideline for
mortality with steroid treatment113. The use of bacterial meningitis. After the review, there was
steroids in neonatal meningitis was still insufficient evidence of benefit of
discouraged. corticosteroid therapy in neonates. Therefore,
Therefor
The European Federation of Neurological the recommendation which prohibits the
Societies (2008) recommended dexa
dexa- administration of corticosteroids in children
methasone to be given with the first d dose of below 3 months of age is sustained114. Further
empiric antimicrobial drug for patients whom research is necessary regarding the routine
pneumococcal or Hib meningitis is use of corticosteroid as an adjuvant therapy.
22
suspected . In adult patients with
pneumococcal meningitis who are either
previously well or not immunocompromised,
dexamethasone is advised to be given together
or shortly
tly prior to the first parenteral dose of
the antibiotic. The recommended dosage is 10
mg every 6 hours for 4 days. For children with
Hib and pneumococcal meningitis, the dosage
is 0.15 mg/kg every 6 hours for 4 days. The
authors also discouraged giving
dexamethasone
xamethasone routinely to patients who have
non-pneumococcal or non-Hib Hib meningitis.
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four-day
day course of rifampicin (20 mg/kg/day) exchange with an infected patient (i.e. kissing).
eliminated 92-97% of Hib pharyngeal carriage The administration of prophylaxis aims to
in contacts118,119,120,121,122,123,124,125,126
5,126
. But for eradicate nasopharyngeal carriage in
children less than 3 months of age, it was household contacts, prevent secondary cases
advised that the dose of rifampicin should be from occurring and hopefully to treat individuals
halved at 10 mg/kg/dayday for 4 days to eradicate currently incubating the disease133.
127
Hib carriage .
Hib vaccination has just been included in a. Haemophilus influenzae
the Expanded Program of Immunization (EPI)
2013 in the Philippines. The pathogen, H.
influenzae type B is still a significant invasive Rifampicin prophylaxis is recommended for
organism that causes severe illnesses, all household contacts or child care contacts
therefore, prophylaxis and vaccination could in cases of H. influenzae type B meningitis,
help lower infection rates secondary to this especially if there is an infant of <2 years old
pathogen. or an immunocompromised person in the
As for N. meningitidis,, nasopharyngeal house.
carriage in asymptomatic, healthy individuals is [Level of evidence: Moderate; Strength of
Recommendation: Strong]
<35% during a single year and rise especially
among close contacts of index cases128;
however, at any one time, only a handful of Chemoprophylaxis is essential since there
individuals will be carrying the pathogen likely are numerous children who lack vaccinations
to cause an epidemic129. N. meningitidis is especially those who live in far-fetched
far rural
transmitted via respiratory
spiratory droplets through areas. The dosage used for chemoprophylaxis
close contacts especially in crowded areas with rifampicin is 20 mg/kg orally once a day
such as dormitories. The highest for 4 days, maximum dose of 600 mg/day127.
nasopharyngeal carriage rates were noted Children below 2 years old are the most
among adolescents and young adults130,131, susceptible for secondary Hib disease, and the
thus adolescents may be the prime source for risk decreases after 4 years of age127. For
disease transmission to other age groups132. children in the household below 5 years old
Nasopharyngeal carriage can be with exposure to an infected person, within
with a
eliminated via prophylaxis with antimicrobial month after the exposure, the secondary attack
drugs: rifampicin for Hib and rifampicin, rate would be 500-800800 times more than the
ceftriaxone or ciprofloxacin for N. meningitidis endemic attack rate for invasive H.
(discussed further below). influenzae134,135.
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after a secondary case, while others give it and even greater reduction in diseases which
after an index case. A systematic review was may have resulted from her protection141.
done on the effectiveness of antibiotics in
preventing meningococcal disease after a b.. Pneumococcal conjugate vaccine
case, which evaluated the occurrence of
Pneumococcal conjugate vaccine is safe
succeeding meningococcal
ngococcal disease cases 11-30
and effective against invasive
days after onset of disease in the index
pneumococcal disease including acute
patient138. There were a total of five studies
bacterial meningitis, pneumonia and
reviewed (4 retrospective cohort studies and
one small trial) upon which meta meta-analysis bacteremia. Also, nasopharyngeal
colonization has declined after introduction
revealed that chemoprophylaxis offers 89%
significantt reduction in risk of subsequent of Pneumococcal conjugate vaccines.
[Level of evidence: High;
meningococcal disease in household contacts Strength of Recommendation: Strong]
of the index patient (risk ratio 0.11, 95% CI
0.02-0.58). The authors recommend the use of Many countries have adopted the use of the
chemoprophylactic drugs against meningo
meningo- pneumococcal conjugate vaccine in routine
coccal disease since antimicrobials to be taken immunization of infants. Surveillance of
are those known to eliminate meningococcal disease have shown that this intervention has
carriage. dramatically reduced the incidence of invasive
pneumococcal disease caused by vaccine
serotypes, which includes acute bacterial
18. What is the role of vaccines in the meningitis and sepsis1422. Herd immunity has
prevention of acute bacterial meningitis? been evident as manifested in reductions in
a. Haemophilus influenzae type B invasive pneumococcal disease even in age
Haemophilus influenzae type B (Hib Hib) vaccine groups not targeted by immunization programs.
is safe and effective against Hib Hib-invasive Decrease nasopharyngeal carriage is seen as
disease including acute bacterial meningitis, the cause of herd immunity.
pneumonia and bacteremia. Also, c. Meningococcal vaccine
nasopharyngeal Hib colonization has declined
Vaccines against N. meningitides
meningiti have a
after introduction of Hib conjugate vaccines.
[Level of evidence: High; limited role in outbreak situations
Strength of Recommendation: Strong] For control of meningococcal outbreaks
caused by vaccine preventable serogroups
In all countries that have used the Hib ( A,C,Y, W 135) MPSV4 or MCV4 vaccines
conjugate vaccine in their national may be used.
immunization program have reported reduction The reactive vaccination strategy relies on
in reported Hib diseases. Several randomized early detection of outbreaks followed
fol by
controlled trials and observational studies on mass vaccination with the vaccine adapted
the conjugated Hib vaccine have shown its to the circulating serogroup.
efficacy as well as effectiveness in preventing Further research is required on the use of
Hib meningitis, pneumonia, bacteremia and vaccines to control transmission of the
other invasive diseases139, 140 After the disease during outbreaks.
introduction of Hib vaccination in national Strength of evidence: Moderate
programs there e has been also substantial Strength of recommendation:
decreases in nasopharyngeal Hib colonization Conditional/Weak.
[Level of evidence: Moderate;
Strength of Recommendation: Conditional/Weak]
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The two meningococcal vaccines used are considered when the disease attack rate is
the Meningococcal polysaccharide vaccine more than 10 cases per 100,000 people based
(MPSV4) and the Meningococcal conjugate on the following factors: 1) the
vaccine (MCV4). The MPSV4 contains purified comprehensiveness of reported cases and the
meningococcal capsular polysaccharides, number
umber of suspected meningococcal cases
given as a single dose of 0.5 mL without bacteriologic confirmation or serogroup
subcutaneously143. Antibody concentrations data; 2) the appearance of additional
offering immune protection are attained within meningococcal cases after the suspected
7-10 days after immunization144. On the other outbreak was recognized; and 3) logistics and
hand, the MCV4
CV4 contains capsular financial resources132.
polysaccharides from serogroups A, C, Y, and
W-135
135 conjugated to a diphtheria toxoid. ection control measures
19. What are the infection
MCV4 is given also as a single dose of 0.5 mL necessary to prevent transmission?
but intramuscularly, achieving protective
antibody concentration within 8 days after The current Healthcare Infection Control
immunization143. Practices Advisory Committee (HICPAC)
Recommendations for routine guidelines should be implemented to
immunization with meningococcal vaccines are prevent transmission of pathogens causing
usually prescribed for specific groups bacterial meningitis.
populations such as adolescents, since 75% of
[Level of evidence:
nce: Moderate; Strength of
meningococcal disease caused by serogroups
Recommendation: Strong]
(A, C, Y, or W-135)
135) occur in children age 11
11-18
145
years old . As such, outbreaks might then The general standard precautions include the
occur in age groups not routinely vaccinated. following146:
Mass vaccination might then be of help in Hand hygiene with proper hand washing
protecting population at risk during using soap and water before and after
132
outbreaks . An outbreak is defined as the handling the patient;
“occurrence of at least three confirmed or Wear personal protective equipment
probable primary cases of meningococcal especially for procedures that may involve
disease caused by the same serogroup in ≤3 contact with blood or body fluids;
months, with a resulting primary attack rate of Respiratory etiquette: symptomatic patients
10 cases per 100,000 population”132. In
≥10 are advised to wear masks to prevent
instances of outbreaks caused by N. spread of infected respiratory droplets; as
meningitidis serogroups A, C, Y or W W-135, well as to maintain separation distance of at
MPSV4 or MCV4 are recommended for people least 3 feet from nearby people in waiting
of at least 11 years of age (MCV4 for >11 areas;
years old, MPSV4 for 2-10 10 years old143. Take Dispose of wastes accordingly in their
note, however, that vaccines have no role in N. proper bins;
meningitidis serogroup B outbreaks since the In pediatrics patients who bring toys to
available vaccines do not cover this serogroup. hospitals, avoid furry ones, only bring those
This highlights the importance of preventive that are easy to clean;
measures since in children less than a year Aseptic technique in all procedures to be
old, N. meningitidis serogroup B causes more done;
than 50% of meningococcal disease146. Proper placement:
ment: patients who pose risk of
During suspected outbreaks, the decision disease transmission to others (e.g. those
to vaccinate the population at risk must be who require droplet precaution) should be
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placed in a single-patient
patient room; if there are The preventive maneuvers must be
insufficient rooms available, patients with performed by all involved persons in the care
the same infection and isolated pathogen of the patient including patient watchers and
may be roomed
oomed in together; in patients visitors to help prevent disease transmission.
sharing rooms, separate them using For those with droplet precautions, placing the
curtains and make sure that they are patient in a single-patient
patient room would
wo suffice,
physically spaced more than 3 feet apart isolation rooms are not necessary.
from each other;
Limit the transport of patients outside the This guideline shall be updated as necessary,
room for only medically necessary but not later than 5 years from the time of
procedures; publication.
Appendix A
Table 7.. Antibiotic Dosages for Neonatal Bacterial Meningitis, Adjusted by Weight and Age
Antibiotic Route Dosage
BW < 2000 g, BW >2000 g, BW < 2000 g, BW >2000 g,
Age 0-7 7 Days Age 0-7 Days Age >7 Days Age >7 Days
Penicillins
Ampicillin IV, IM 50 mg/kg q12h 50 mg/kg q8h 50 mg/kg q8h 50 mg/kg q6h
Penicillin G IV 50,000 U/kg q12h 50,000 U/kg q8h 50,000 U/kg q8h 50,000 U/kg q6h
Oxacillin IV, IM 50 mg/kg q12h 50 mg/kg q8h 50 mg/kg q8h 50 mg/kg q6h
Ticarcillin IV, IM 75 mg/kg q12h 75 mg/kg q8h 75 mg/kg q8h 75 mg/kg q6h
Cephalosporins
Cefotaxime IV, IM 50 m mg/kg g 50 mg/kg q8h 50 mg/kg q8h 50 mg/kg q6h
q12h
Ceftriaxone IV, IM 50 mg/kg q d 50 mg/kg q d 50 mg/kg q d 75 mg/kg q d
Ceftazidime IV, IM 50 mg/kg q12h 50 mg/kg q8h 50 mg/kg q8h 50 mg/kg q8h
Table 8.. Dosages and Dosing Intervals for Intravenous Antimicrobials in Infants and Children With
Bacterial Meningitis
Antibiotic IV Dosage Maximum Daily Dose Dosing Interval
Ampicillin 400 mg/kg/day 6-12 g q6h
Vancomycin 60 mg/kg/day 2-4 g q6h
Penicillin G 400,000 U/kg/day 24 million U q6h
Cefotaxime 200-300
300 mg/kg/day 8-10 g q6h
Ceftriaxone 100 mg/kg/day 4g q12h
Ceftazidime 150 mg/kg/day 6g q8h
Cefepime* 150 mg/kg/day 2-4 g q8h
Meropenem 120 mg/kg/day 4-6 g q8h
*Experience with this agent in pediatric patients is minimal; it is not licensed for treatment of
meningitis.
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Table 9.. Chemoprophylaxis for Bacterial Meningitis Caused by Haemophilus influenzae or Neisseria
meningitidis
Age of
Causative Organism Drug Name Dosage
Contact
Rifampin Adults >600 mg PO q d for 4 days
Haemophilus 20 mg/kg PO q d for 4 days; not to exceed 600
>1 month
influenzae mg/dose
< 1 month >10 mg/kg PO q d for 4 days
Rifampin Adults 600 mg PO q12h for 2 days
10 mg/kg PO q12h for 2 days; not to exceed 600
>1 month
mg/dose
Neisseria meningitidis <1 month >5 mg/kg PO q12h for 2 days
Ceftriaxone >15 years 250 mg IM once
<15 years >125 mg IM once
Ciprofloxacin >18 years >500 mg PO once
Contacts within the hospital setting*: setting*
Appendix B. Definitions of Terms for includes individuals with direct exposure to the
Prevention of Infection index case’ respiratory secretions (such as
Definition of terms: healthcare workers in direct care of the index
Index case:: the index case is the case and close contacts of the index case such
individual who presents with the disease in as those individuals who share a hospital room
absence of known exposure to another patient with the index case) prior to the index case’s
with the disease79. completion of 48 hours of clearance
Secondary case:: presentation of the antibiotics29.
disease in close contacts of the index case *As defined for Hib cases
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