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University of Khartoum
Graduate College
Medical and Health Studies Board
Bacterial Isolates and Antimicrobial Susceptibility in Patients Attending the E.N.T
Hospital in Khartoum
By
Dr. Nada Abdallah Basheer
M.B.B.S (University of Khartoum, 1995)
A thesis submitted in partial fulfillment for the requirements of the Degree of Clinical MD
in Clinical Pathology, 2010
Supervisor
Dr. Nageeb Suleiman Saeed
MD, MRCpath
Associate Professor of Microbiology
Head Department of Microbiology
Faculty of Medicine
University of Khartoum
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CONTENTS
Page No.
Dedication
i
Acknowledgment
ii
Abbreviations
iii
English abstract
iv
Arabic abstract
vi
List of tables
viii
List of figures
ix
CHAPTER ONE
1. Introduction and literature review
1
1.1. Otitis media
1
1.1.1. Definition
1
1.1.2. Types of otitis media
1
1.1.2.1. Acute Otitis Media (AOM)
1
1.1.2.2. Otitis Media with effusion (OME)
3
1.1.2.3. Chronic suppurative Otitis Media (CSOM)
3
1.1.2.4. Otitis media without effusion
4
1.1.3. Epidemiology
5
1.1.4. Anatomy of the ear
6
1.1.5. Pathophysiology
9
1.1.6. Symptoms
11
1.1.7. Diagnosis
13
1.1.8. Mortality/Morbidity
17
1.1.9. Treatment
18
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1.1.9.1. Antibiotic Selection
20
1.1.9.2. Bacterial resistance after antibiotic therapy failures
24
1.1.9.3. Surgical treatment
25
1.1.10. Causative agents of OM and their antibiotics susceptibility
26
1.2. Objectives
31
1.2.1. General Objective
31
1.2.2. Specific Objectives
31
CHAPTER TWO
2. Patients and methods
32
2.1. Study design
32
2.2. Study period
32
2.3. Study Area
32
2.4. Study population
32
2.5. Sample size
32
2.6. Site of collection
33
2.7. Culture
33
2.8. Data analysis
35
CHAPTER THREE
36
3. Results
CHAPTER FOUR
4. Discussion
49
4.1. Conclusion
55
4.2. Recommendations
57
References
58
Appendices
62
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First of all thanks to ALLAH for giving me strength and power to
complete this study.
I would like to thank my supervisor Dr.Nageeb Suleiman Saeed, The
General Director of the National Health Laboratory and The Head of the
Microbiology Department, Faculty of Medicine U of K, for his great patience and
valuable guidance.
I would like also to give my great thanks to all my colleagues in
Bacteriology Department in National Health Laboratory, for their help and
support. Especially the senior technologists Ali Khogaly, Mohammed A. Gorga,
Amina A, and Ibraheem Ali Elhag.
My great thanks to Mr .Hasan the lab assistant in the MD lab and to my
colleagues in the ENT Hospital for their great help and cooperation.
My thanks to Mr. Hassan Ali the analyst, for his great help ,and to the
typist Widad in the Faculty of Medicine, and to all who gave me moral support or
Duaa to Allah to aid me in my efforts.
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Abbreviations
AOM
Acute otitis media
CSOM
Chronic suppurative otitis media
MEE
Middle ear effusion
NCCLS
National Committee for clinical laboratory standards
OM
Otitis media
OME
Otitis media with effusion
TM
Tympanic membrane
TT
Tympanostomy tube
UK
United Kingdom
URI
Upper respiratory tract infection
US
United States
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ABSTRACT
Background: Otitis Media is one of the common diseases especially
in childhood, it had great influence on work and school attendance and it
may lead to hearing loss if not properly diagnosed and treated.
The objectives of this study are to determine the prevalence of the
common aerobic bacteria causing otitis media among Sudanese population
and their pattern of antimicrobial sensitivity.
Methods: This descriptive study was carried out in Khartoum State
at the ENT Hospital, out-patient clinic during Dec. 2008 to March 2009.
Data were collected by a questionnaire and swabs were taken from ear
discharge randomly. Isolation, identification and in-vitro sensitivity tests
were performed on all isolates.
Results: A hundred and four patients were studied, male to female
ratio was 3 : 2, children represented 66.7%, while adults were 43.3%.
Bacterial isolates represented 64% of the specimens; fungal isolates were
6.5%, while the rest of specimens showed no pathogenic organisms. Acute
otitis media (AOM) comprised 41% of all patients, children represented
88% of them, while chronic suppurative otitis media (CSOM) were 59%
and was mainly in adults. The most prevalent organisms causing acute
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otitis media were Streptococcus pneumomiae (50%), Staphylococcus aureus
(38%) and Strept pyogene (12%). Regarding chronic otitis media, Proteus spp
was the most common organism (33%) followed by Staphylococcus aureus
(30%) and Psuedomonas spp (27%). Most Staph aureus strains (90%) were
penicillin resistant and 84% were sensitive to erythromycin. Regarding
Strept. Pneumoniae, 93% were sensitive to Coamoxycalve, erythromycin
sensitivity was 86%. Proteus spp. sensitivity to both cefotaxime and
ceftriaxone was 86%, and their sensitivity to both ciprofloxacin and
gentamicin was 79%. Pseudomonas spp. isolates were sensitive to
ceftazidime (82%), carbinicillin (73%), cefotaxime (64%) and amikacin was
55% sensitive.
Conclusion: This study has shown the main causative organisms of
AOM and CSOM and their susceptibility pattern of antibiotic tested. This
information can be used as guideline for empiric therapy of otitis media.
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LIST OF TABLES
Page No.
Table 1-1: Treatment recommendations for otitis media
20
Table 1: Distribution of patients according to age groups
37
Table 2: Number and percentage of bacterial isolates
37
Table 3: List of organisms isolated
38
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LIST OF FIGURES
Page No.
Fig. 1-1: The anatomy of the middle ear
8
Fig. 1: Types of otitis media
39
Fig. 2: Relation between age and types of otitis media
40
Fig. 3: Relation between organisms isolated and
types of otitis media
41
Fig. 4: Susceptibility of Staph. aureus
42
Fig. 5: Susceptibility of Strept. Pneumoniae
43
Fig. 6: Susceptibility of Strept. pyogenes
44
Fig. 7: Susceptibility of Proteus sp.
45
Fig. 8: Susceptibility of Pseudomonas sp.
46
Fig. 9: Susceptibility of E. coli
47
Fig. 10: Susceptibility of Klebsiella sp.
48
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1. INTRODUCTION AND LITERATURE REVIEW
1.1. Otitis media:
1.1.1. Definition:
Otitis media (OM) is any inflammation of the middle ear
without reference to etiology or pathogenesis. OM can be classified
into many types on the basis of etiology, duration, symptomatology,
and physical findings. (1)
Bacterial otitis media in the majority of cases is caused by
upper respiratory tract pathogens like Streptococcus pyogenes
,Streptococcus pneumoniae, Moraxella catrrhalis
and
Haemophilus
influenzae. Other possible pathogens include Staphylococcus aureus,
Klebsiella sp., Proteus sp., Escherichia coli, and other coliforms,
Psuedomonas sp, and Bacteroides sp. (2)
1.1.2. Types of otitis media:
1.1.2.1. Acute Otitis Media (AOM):
The rapid and short onset of signs and symptoms of
inflammation in the middle ear is characteristic of AOM. Acute
suppurative otitis media and purulent otitis media are synonyms
still used by some but are not recommended terms. One or more
1
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local or systemic signs are present: otalgia (or pulling of the ear in
the young infant), otorrhea, fever, recent onset of irritability,
anorexia, vomiting, or diarrhea. The tympanic membrane is full or
bulging, opaque, and has limited or no mobility to pneumatic
otoscopy, all of which indicate middle-ear effusion. Erythema of the
eardrum is an inconsistent finding.
AOM has been defined in the clinical practice guideline
presented by the American Academy of Pediatrics and the
American Academy of Family Physicians, the criteria for AOM
were: a history of acute onset of signs and symptoms, the presence
of middle ear effusion, and signs and symptoms of middle ear
inflammation. Furthermore, the following elements were described:
recent, usually abrupt, onset of signs and symptoms of middle ear
inflammation and middle ear effusion that is indicated by any of the
following: bulging of the eardrum , limited or absent mobility of the
tympanic membrane, air-fluid level as visualized through the
tympanic membrane, or otorrhea.(3)
2
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1.1.2.2. Otitis Media with effusion (OME):
The persistence of an effusion beyond three months without
signs of infection defines otitis media with effusion,(3)formerly
termed serous OM or secretory OM, is Middle ear effusion (MEE ) of
any duration that lacks the associated signs and symptoms of
infection (e.g., fever, otalgia, irritability). OME usually follows an
episode of AOM.(1) Pneumatic otoscopy frequently reveals either a
retracted or convex tympanic membrane with impaired mobility.
Fullness or even bulging may be visualized in some patients. An airfluid level bubbles, or both may be observed through a translucent
tympanic membrane. The most important distinction between otitis
media with effusion and AOM is that the signs and symptoms of
acute infection (e.g., otalgia and fever) are lacking in otitis media
with effusion. Hearing loss is usually present in both conditions.(4).
1.1.2.3. Chronic suppurative Otitis Media (CSOM):
Is a chronic inflammation of the middle ear that persists at
least 6 weeks and is associated with otorrhea through a perforated
Tympanic membrane (TM), an indwelling tympanostomy tube (TT),
or a surgical myringotomy.(1)
3
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CSOM involves a perforation in the eardrum and active
bacterial infection within the middle ear space for several weeks or
more. There may be enough pus that drains to the outside of the ear
or the purulence may be minimal enough to only be seen on
examination using a binocular microscope. This disease is much
more common in persons with poor Eustachian tube function.
Hearing impairment often accompanies this disease and the patient
is usually asymptomatic.(5)
1.1.2.4. Otitis media without effusion:
Is a stage of middle-ear inflammation in which the mucosa of
the middle ear is involved, but no effusion is present. This stage of
otitis media was recently substantiated, employing tympanocentesis
as confirmatory evidence. This stage classically precedes the
development of an acute effusion and can be associated with the
acute onset of otalgia. One form of this stage of inflammation is
commonly encountered in infants and children who have
functioning tympanostomy tubes in place. They typically present
with acute otalgia, with or without fever, and erythema of the
inferior portions of the tympanic membrane, but no otorrhea is
present.(6)
4
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Middle-ear effusion: designates a liquid in the middle ear, but
not etiology, pathogenesis, pathology or duration. An effusion may
be serous (thin, watery liquid), mucoid (thick, viscid, mucus-like
liquid), purulent (pus-like liquid) or a combination of these. An
effusion can be the result of either AOM or otitis media with
effusion. The effusion can be of recent onset (acute) or longer lasting
(subacute or chronic). Persistent middle-ear effusion is an effusion
that persists in the middle ear after an episode of AOM.
Otorrhea: is a discharge from the ear originating at one or
more of the following sites: the external auditory canal, middle ear,
mastoid, inner ear, or intracranial cavity.(6)
1.1.3. Epidemiology:
Otitis media (OM) is the second most common disease of
childhood, after upper respiratory infection (URI). OM is also the
most common cause for childhood visits to a physician's office.(1)
Its incidence is 10-20% for each year of life up to 6 years of
age and then decreases dramatically to less than 1% by the age of 12.
By definition, these patients require antimicrobial therapy and
therefore, this diagnosis accounts for the greatest proportion of
antimicrobial prescriptions. (5)
5
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Acute otitis media is the most common infection for which
antibiotics are prescribed for children in the USA. Direct and
indirect costs of treatment and time lost from school and work
because of acute otitis media totaled nearly 3$ billion in 1995. Acute
otitis media is most common between 6 and 24 months of age; by
age three, more than 80% of children have been diagnosed.(3)
In the United Kingdom about 30% of children aged under
3 years visit their general practitioner with acute otitis media each
year, and 97% receive antimicrobial treatment. About 1 in
10 children will have an episode of acute otitis media by 3 months of
age. It is the most common reason for outpatient antimicrobial
therapy. (7)
In the less developed nations, OM is extremely common and
remains a major contributor to childhood mortality resulting from
late presenting intracranial complications. (1)
1.1.4. Anatomy of the ear:
The ear is functionally and anatomically divided into three parts:
A) The External Ear: that portion external to the tympanic
membrane. It serves chiefly to protect the tympanic membrane,
but also collects and directs sound waves and plays a role in
6
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sound localization. The skin of the external ear normally
migrates laterally from the umbo of the malleus in the tympanic
membrane to the external auditory meatus (at a rate of 2-3 mm
per day). This is a unique and essential mechanism for
maintaining patency of the canal. (9)
B) The Middle Ear: This is an air-containing space which
communicates with the nasopharynx via the eustachian tube. It
is normally sealed laterally by the tympanic membrane. Its
function is to transmit and amplify sound waves from tympanic
membrane to the stapes footplate converting energy from air
medium to a fluid medium of the membranous labyrinth.
The tympanic membrane is an ovoid, three-layered structure
consisting of squamous epithelium laterally, respiratory mucosa
medially, and an intervening fibrous layer. It normally has a
conical shape, with the apex maintained medially by the support
of the malleus. The fibrous layer thickens laterally to form the
annulus, an incomplete ring which is attached to surrounding
bone. Superior to the lateral process of the malleus, this ring is
deficient, and this area is known as the pars flaccida. The
majority of the drum is composed of the pars tensa.
7
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C) The Inner Ear: Consists of a fluid-filled labyrinth which
functions to convert mechanical energy into neural impulses.
The bony labyrinth is subdivided into smaller compartments by
the membranous labyrinth. Fluid surrounding the membranous
labyrinth is called perilymph; fluid within is called endolymph.(9)
Figure 1-1: shows the anatomy of the middle ear
8
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1.1.5. Pathophysiology:
Genetic, infectious, immunologic, and environmental factors
predispose to ear infections. In most cases, an allergy or upper
respiratory tract infection causes congestion and swelling of the
nasal mucosa, nasopharynx, and eustachian tube.
Obstruction at the eustachian tube results in accumulation of
middle ear secretions; secondary bacterial or viral infection of the
effusion causes suppuration and features of acute otitis media. The
effusion may persist for weeks or months after the infection
resolves. Otitis media with effusion may occur spontaneously as a
result of Eustachian tube dysfunction after acute otitis media. (5)
1.1.5.1. Genetic base:
Recurrent and chronic forms of otitis media are known to
have a strong genetic component, but nothing is known of the
underlying genes involved in the human population. a previously
identified novel semi-dominant mouse mutant allele, Jeff, in which
the heterozygotes develop chronic suppurative otitis media and
represent a model for chronic forms of otitis media in humans. They
demonstrate that Jeff carries a mutation in an F-box gene, Fbxo11.
Fbxo11 is expressed in epithelial cells of the middle ears from late
9
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embryonic stages through to day 13 of postnatal life. In contrast to
Jeff heterozygotes, Jeff homozygotes show cleft palate, facial clefting
and perinatal lethality. This study also isolated and characterized an
additional hypomorphic mutant allele, Mutt. Mutt heterozygotes do
not develop otitis media but Mutt homozygotes also show facial
clefting and cleft palate abnormalities.(10)
FBXO11 is one of the first molecules to be identified,
contributing to the genetic etiology of otitis media. In addition, the
recessive effects of mutant alleles of Fbxo11 identify the gene as an
important candidate for cleft palate studies in the human
population. (10)
1.1.5.2. Factors affecting risk of acute otitis media:(21)
• Age: Maximal incidence between 6 and 24 months of age;
eustachian
tube
shorter
and
less
angled
at
this
age.
Underdeveloped physiologic and immunologic responses to
infection in children.
• Breastfeeding: it is for at least three months is protective; this
effect may be associated with position maintained during
breastfeeding, suckling movements, and protective factors in breast
milk.
10
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• Daycare attendance: contact with multiple children and daycare
providers facilitates spread of bacterial and viral pathogens.
•Exposure to cigarette smoke: Increased incidence with sigarette
smoke and air pollution, especially if parents smoke.
•Male sex: Slightly increased incidence.
•More than one sibling living at home:
• Previous antibiotic use & previous otitis media:
•Season: Increased incidence in autumn and winter.
•Underlying pathology: Increased incidence in children with
allergic rhinitis, cleft palate, Down syndrome.
1.1.6. Symptoms:
Otalgia: young children may exhibit signs of otalgia by
pulling on the affected ear or ears or pulling on the hair. Otalgia
apparently occurs more often when the child is lying down.
Otorrhea: Discharge may come from the middle ear through a
recently perforated TM, through a preexisting TT, or through
another perforation. For trauma patients, excluding a basilar skull
fracture with associated cerebrospinal fluid (CSF) otorrhea is
important.
11
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Headache and concurrent URI symptoms (e.g., cough,
rhinorrhea, sinus congestion). Generally, two thirds of children with
AOM have a history of fever, although fevers greater than 40°C are
uncommon and may represent bacteremia or other complications.
Irritability may be the sole early symptom in a young infant or
toddler. A history of lethargy, although nonspecific, is a sensitive
marker
for
sick
children
and
should
not
be
dismissed.
Gastrointestinal tract symptoms include anorexia, nausea, vomiting,
and diarrhea. (1)
OME and CSOM their history includes any of the following:
• Hearing loss: Most young children cannot provide an accurate
history. Parents, caregivers, or teachers may suspect a hearing loss
or describe the child as inattentive.
• Tinnitus: This is possible, although it is an unusual compliant.
• Vertigo: Although true vertigo (i.e., room-spinning dizziness) is a
rare compliant in uncomplicated OM, parents may report some
unsteadiness or clumsiness in a young child with AOM.
• Otalgia: Intermittent otalgia tends to worsen at night.(1)
12
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1.1.7. Diagnosis:
Acute otitis media is over diagnosed. Symptoms are neither
sensitive nor specific for the diagnosis of otitis media; fever and ear
pain are present in only one half of patients. Undue reliance on one
feature redness of the tympanic membrane and failure to assess
tympanic membrane mobility with pneumatic otoscopy contribute
to inaccurate diagnoses. Adequate visualization of the tympanic
membrane is often impaired by low light output from old otoscope
bulbs and blockage of the ear canal by cerumen. Distinguishing
acute otitis media from otitis media with effusion is important
because antibiotics are seldom indicated for the latter condition. A
key differentiating feature is the position of the tympanic
membrane: it is usually bulging in acute otitis media and in a
neutral position or a retracted position in otitis media with effusion.
Tympanometry and acoustic reflectometry can be useful adjunctive
tools to confirm the presence of fluid in the middle ear. Selective use
of tympanocentesis in cases of refractory or recurrent middle ear
disease can help guide appropriate therapy and avoid unnecessary
medical or surgical interventions. (11)
13
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1.1.7.1. Pneumatic otoscopy:
Detection of middle ear effusion by pneumatic otoscopy is key
in establishing the diagnosis of acute otitis media.(7) The tympanic
membrane normally is convex, mobile, translucent, and intact; a
normal color and mobility of the membrane indicate that otitis
media is unlikely.(5)
The tympanic membrane can not be adequately seen while
partially occluded by cerumen. Cerumen removal by curette is
essential and should be regularly used. If the wax is dry or deep in
the auditory canal then cerumenolytics and/or warm water
irrigation may necessary. Pneumatic otoscopy has been advocated
as an important adjunct to assist in diagnostic accuracy of AOM. (13)
Four characteristics of the TM should be evaluated and described in
every
examination
(position,
mobility,
colour,
degree
of
translucency). The normal TM is in the neutral position (neither
retracted nor bulging), pearly gray, translucent and responds briskly
to positive and negative pressure, indicating an air filled space. The
abnormal TM may be retracted or bulging, and immobile or poorly
mobile to positive and/or negative air pressure. The colour of the
eardrum is of minor importance although patients with AOM more
14
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often have a red TM. The key differentiating features of AOM
compared to OME on physical exam relate to TM position. In AOM
the TM almost always is bulging and in OME it is usually retracted
or, occasionally, it is in neutral position. The TM is thickened in both
AOM and OME, thereby reducing visibility through it. Sometimes a
yellow or grayish middle ear effusion can be seen behind the TM in
either condition. (5)
1.1.7.2. Tympanometry and acoustic reflectometry:
Each have attributes which make them of value in providing
information about the possible presence of a middle ear effusion.
The sensitivity, specificity, positive predictive value and negative
predictive value of the two instruments have been assessed in
comparison
with
pneumatic
otoscopy,
audiometry
and
tympanocentesis findings. As a result both of them have some
limitations. Acoustic reflectometry has the advantage of not
requiring a seal within the canal which improves its usefulness in
the crying child because a reading can be obtained when a child
stops crying to take a breath. Tympanometry provides additional
information about actual pressures within the middle ear space. (14)
15
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1.1.7.3. Tympanocentesis:
Tympanocentesis followed by aspiration and culture of
middle ear fluid samples, is useful in children who are toxic, have
failed multiple courses of antibiotics, or have immune deficiencies.
Although negative nasopharyngeal cultures correlate well with
negative middle ear fluid cultures, they are not routinely
recommended. Selective use of tympanosynthesis may improve
diagnostic accuracy because it validates or
refutes the physicians’
impression after visual examination. Certainly proper restraint of
the patient and excellent visualization of the TM are essential; mild
sedation may also be helpful in some cases. Tympanocentesis
should be performed and it is beneficial. (15)
1.1.7.4. Radiography:
Radiographic evaluation of the temporal bone is indicated
when complications or sequelae of otitis media are suspected or
present. Plain radiographs are of limited value in the diagnosis of
mastoiditis or cholesteatoma; computed tomography(CT) and
magnetic resonance imaging (MRI) are more precise and should be
obtained if a suppurative intratemporal or intracranial complication
is suspected.(3)
16
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1.1.8. Mortality/Morbidity:
In about 80% of children the condition resolves without
antibiotic treatment in about three days.(7) In US mortality rates are
extremely low in this era of antimicrobial therapy (<1 death per
100,000 cases). A study that examined the causes of death in Los
Angeles County Hospital from 1928-1933, years prior to the advent
of sulfa, showed 1 in 40 deaths was caused by intracranial
complications of OM. Morbidity from this disease remains
significant, despite frequent use of systemic antibiotics to treat the
illness and its complications. In developing nations with limited
access to primary medical care and modern antibiotics, mortality
rates are higher. (4)
A) Intratemporal complications:
-
Hearing loss (conductive and sensorineural).
-
TM perforation (acute and chronic).
-
Chronic suppurative OM (with or without cholesteatoma).
-
Cholesteatoma.
-
Tympanosclerosis.
-
Mastoiditis.
-
Petrositis.
17
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-
Labyrinthitis.
-
Facial paralysis.
-
Cholesterol granuloma.
-
Infectious eczematoid dermatitis.
B) Intracranial complications:
Meningitis, subdural empyema, brain abscess, extradural
abscess, lateral sinus thrombosis and otitic hydrocephalus. (4)
1.1.9. Treatment:
Observation is an acceptable option in healthy children with
mild symptoms. Antibiotics are recommended in all children
younger than six months, in those between six months and two
years if the diagnosis is certain, and in children with severe
infection. High-dosage amoxicillin (80 to 90 mg per kg per day) is
recommended
as
first-line
therapy.
Macrolide
antibiotics,
clindamycin, and cephalosporins are alternatives in penicillinsensitive children and in those with resistant infections. Patients
who do not respond to treatment should be reassessed. Hearing and
language testing is recommended in children with suspected
hearing loss or persistent effusion for at least three months, and in
those with developmental problems.(1)
18
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Should antibiotics be used to treat AOM?
Antimicrobial therapy is one of the cornerstones in the
management of AOM but some studies have suggested that its
routine use is not indicated. Nonetheless, in the preantibiotic era,
complications of AOM such as mastoiditis were far more common
than they are today; this difference may be due to the current
routine use of antibiotics. A recent meta-analysis of 5400 children
with AOM indicated that antimicrobial therapy enhanced the
‘primary control’ by 13.7% despite a spontaneous recovery in 81% of
cases. Because it is probably not possible to determine which cases
of AOM will result in suppurative complications, it is likewise not
possible to determine which cases require antimicrobial therapy and
which will resolve spontaneously. Therefore, it appears prudent to
consider all cases of AOM candidates for antimicrobial therapy in
order to minimize the likelihood of complications. Some experts
recommend watchful waiting for 48 to 72 h before initiating
antibiotic therapy. This approach may be feasible in children over
two years of age if good follow-up can be assured; therefore,
decisions about whether to withhold antibiotics therapy initially
must be made on a patient-by-patient basis.(12)
19
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Table 1-1: CDC Working Group Treatment Recommendations for Acute
Otitis Media*
Antibiotics in
prior month
Day 0
Clinically defined
treatment failure on day 3
Clinically defined
treatment failure
on days 10 to 28
No
High-dose
amoxicillin;†
usual-dose
amoxicillin
High-dose amoxicillinclavulanate
(Augmentin);‡cefuroxime
axetil (Ceftin);
intramuscular ceftriaxone
(Rocephin)‡
Same as day 3
Yes
High-dose
amoxicillin;
high-dose
amoxicillinclavulanate;
cefuroxime
axetil
Intramuscular ceftriaxone;‡ High-dose
clindamycin;§ or
amoxicillintympanocentesis
clavulanate;
cefuroxime axetil;
intramuscular
ceftriaxone;‡ or
tympanocentesis
CDC = Centers for Disease Control and Prevention.
*--Recommended drugs are those for which strong evidence for efficacy
currently exists. Other drugs also may prove efficacious.
‡--High-dose amoxicillin is 80 to 90 mg per kg per day. High-dose amoxicillinclavulanate is 80 to 90 mg per kg per day of amoxicillin component, with 6.4
mg per kg per day of clavulanate (requires newer formulations or combination
with amoxicillin).
‡--Intramuscular ceftriaxone has been documented to be efficacious in acute
otitis media treatment failures if three daily doses are used.
§--Clindamycin is not effective against Haemophilus influenzae or Moraxella
catarrhalis.
1.1.9.1. Antibiotic Selection:
Acute otitis media: High-dosage Amoxicillin (80 to 90 mg
per kg per day) divided into two daily doses for 10 days is
recommended as first-line antibiotic therapy in children with acute
otitis media. In children older than six years with mild to moderate
disease, a five- to seven-day course is adequate.
20
(1)Amoxicillin
is
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effective, safe, and relatively inexpensive, and it has a narrow
microbiologic spectrum. First-line treatment with amoxicillin is not
recommended in children with concurrent purulent conjunctivitis,
after antibiotic therapy within the preceding month, in children
taking amoxicillin as chemoprophylaxis for recurrent acute otitis
media or urinary tract infection, and in children with penicillin
allergy.(1) Cephalosporins may be used in children allergic to
penicillin if there is no history of urticaria or anaphylaxis to
penicillin. If there is a history of penicillin-induced urticaria or
anaphylaxis, a macrolide (e.g., azithromycin ,clarithromycin
or
clindamycin may be used. A single dose of parenteral ceftriaxone
(50 mg per kg) may be useful in children with vomiting or in whom
compliance is a concern. Single-dose azithromycin is safe and
effective in uncomplicated acute otitis media and compares well
with longer courses of azithromycin or other antibiotics.(17)
Persistent acute otitis media: If there is no clinical
improvement within 48 to 72 hours, the patient must be reassessed
to confirm the diagnosis, exclude other causes of illness, and initiate
antibiotic therapy in those on symptomatic treatment alone. Patients
who are already taking antibiotics should be changed to second-line
21
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therapy.
Options
include
high-dose
amoxicillin/clavulanate
cephalosporins, and macrolides. Parenteral ceftriaxone administered
daily over three days is useful in children with emesis or resistance
to amoxicillin/clavulanate. For children who do not respond to
second-line antibiotics, clindamycin and tympanocentesis are
appropriate options. Although it is not approved for use in children,
levofloxacin is effective in children who have persistent or recurrent
acute otitis media.(18)
Recurrent Acute Otitis Media: Most children with recurrent
acute otitis media improve with watchful waiting. Although
antibiotic prophylaxis may reduce recurrence, there are no widely
accepted recommendations for antibiotic choice or prophylaxis
duration. Minimizing risk factors (e.g., exposure to cigarette smoke,
pacifier use, bottle feeding, and daycare attendance) decreases
recurrence.
Heptavalent
pneumococcal
vaccine
reduces
the
incidence of acute otitis media, but it does not reduce recurrence.(5).
Otitis media with effusion: Persistent middle ear effusion
after resolution of acute otitis media does not indicate treatment
failure and requires only monitoring and reassurance. Risk factors
for persistent acute otitis media with effusion include hearing loss
22
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greater than 30 dB (decibels), prior tympanostomy tube placement,
adenoid hypertrophy, and onset during summer or fall.(19)
Clinical examination, pneumatic otoscopy, and tympanometry
may be performed during the observation period. There is no role
for antihistamines and decongestants; Oral and topical intranasal
corticosteroids alone or in combination with an antibiotic produce
faster short-term resolution of otitis media with effusion, but there is
no evidence of long-term benefit. Auto inflation (i.e., opening the
Eustachian tube by raising intranasal pressure) is useful in older
children with persistent acute otitis media with effusion who are
able to perform the Valsalva maneuver. (20)
Children older than two years who have otitis media with
effusion and no developmental issues must be seen at three- to sixmonth intervals until effusion resolves, hearing loss is identified, or
structural abnormalities of the tympanic membrane or middle ear
are suspected. Hearing and language testing is recommended in
patients with suspected hearing loss or persistent effusion for at
least three months, or when developmental problems are identified.
Children with hearing loss of 20 dB or less who do not have speech,
language, or developmental problems can be observed. Those with
23
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hearing loss of 21 to 39 dB can be observed or referred for surgery,
and those with hearing loss of 40 dB or more should be referred for
surgery.(3)
1.1.9.2. Bacterial resistance after antibiotic therapy failures:
During the 1980s, H. influenzae was the most common (46 to
62 percent) pathogen isolated in patients who failed to respond to
initial treatment of acute otitis media. Currently, it appears that
S. pneumoniae, particularly penicillin-resistant strains, accounts for
an increasing number of pathogens in patients who fail to respond
to antibiotic therapy. The highest risk for penicillin-resistant
S. pneumoniae occurs in patients who have been treated recently with
antibiotics (particularly within the preceding month) or who are not
improving during a course of antibiotic therapy.(21)
With persistent and recurrent acute otitis media, treatment
success rates can be expected to be in the range of 60 to 70 percent,
even when the most efficacious broad-spectrum oral antibiotics are
chosen. Currently, minimal data are available regarding the
treatment of acute otitis media caused by highly penicillin-resistant
S. pneumoniae. Thus far, only five antibiotics--high-dose amoxicillin,
amoxicillin-clavulanate , cefuroxime , cefprozil and ceftriaxone --
24
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have demonstrated a modest degree (60 to 80 percent) of clinical
efficacy in the treatment of acute otitis media caused by penicillinresistant S. pneumoniae.Studies of other broad-spectrum agents are
currently under way.(21)
1.1.9.3. Surgical treatment:
The primary objective of surgical treatment of chronic serous
otitis media is to reestablish ventilation of the middle ear, keeping
the hearing at a normal level and preventing recurrent infection.
This involves myringotomy with insertion of a ventilation tube and,
at times, adenoidectomy.(22)
Myringotomy (an incision in the eardrum membrane) is
performed to remove middle ear fluid. A ventilation tube is inserted
to prevent the incision from healing and to insure middle ear
ventilation. The ventilation tube temporarily takes the place of the
eustachian tube in equalizing middle ear pressure. This plastic tube
usually remains in place for three to nine months during which time
the eustachian tube blockage should subside. When the tube
dislodges, the eardrum heals; the eustachian tube then resumes its
normal pressure equalizing function.
25
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In rare cases the membrane does not heal following
dislodgement of the tube. The perforation may be repaired later.
In adults, myringotomy and insertion of ventilation tube is
usually performed in the clinic under local anesthesia. In children
general anesthesia is required. The adenoids can be removed if
enlarged. In some difficult cases it is necessary to insert a more
permanent type of tube, the "mesh" ventilation tube. This tube is
more difficult to insert but frequently will remain in place until
removed. In children, removal may require an anesthetic. At times a
permanent membrane perforation develops when the tube is
dislodged or removed. If this perforation persists it can be repaired
at a later date when the eustachian tube blockage has subsided. (22)
1.1.10. Causative agents of OM and their antibiotics susceptibility:
A descriptive study was conducted in Khartoum state at the
ENT hospital, out-patient clinic by Mohammed B. (April2001March2002), fifty samples were collected from different ages and
sexes. It revealed that Staphylococcus aureus was responsible for
(31.4%) of cases, Proteus sp.(23%), Steptococcus sp. (14.4%), Klebsiella
sp(2.8). Most Staph. aureus sp were sensitive to Gentamicin,
Norfloxacin
and
Ciprofloxacin
26
,resistant
to
Ampicillin,
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Cotrimoxazole, and Streptomycin. Proteus sp. Were sensitive to
Gentamicin, Ciprofloxacin, Norfloxacin,and Cefixime. Resistant to
Ampicillin, Cotrimoxazol, and Ceftriaxon. Other isolates were
sensitive to Gentamicin, least sensitive to Ampicillin Tetracycline
and Streptomycin. (23)
In King Abdul-Aziz University Hospital, a study done by
Attallah (2000), eighty eight patient diagnosed as chronic
suppurative otitis media, the common isolates were Pseudomonas sp.
(51%), Staph aureus (31%), Proteus sp.(17%), fungi were (17%).(24)
Another study conducted at King Abdul-Aziz University
Hospital, by Eiad, et al (2001) for patient diagnosed as acute otitis
media , showed that Streptococcus pneumoniae (25%), Haemophilus
influenzae (36.6%), St.pyogenes (20%), Staph.aureus (15%), Maroxella
catarrhalis(1.6%), Others show no growth .The resistance pattern of
Staph.aureus to Penicillin was(36%),while (100%)to both St.pyogen
and M.catarrhalis. fifty one percent of St.aureus were Penicillin
resistant and (6.7%) were Methecillin resistance isolates.(25)
A total of 106 specimens were cultured from middle ear
discharge in Addis-Ababa Hospital by Melaku, Iulseged (1999)that
27
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showed that (37.7%) Proteus sp. followed by Staph aureus,
Psuedomonas sp. and other Gm-ve Enterococci.(26)
In University of Eyciyes, School of medicine, Keysen, Turkey.
In a study conducted by Nicro (2000) exudates of (183) patients with
Chronic otitis media aerobic isolates were Psuedomonas sp.Staph
aureus, and Klebsiella sp. All were sensitive to topical application of
single dose (0.2%) Ciprofloxacin or combination of PolymixinB and
Hydrocortisone suspension. (27)
Another study conducted by Yavuz K.Ismail (2002) on
bacterial isolates from children of AOM done in Sel.UK. University
Ankara, showed that Sterpt.pneumoniae (39%), Haemophilus influenzae
(27%), Moraxella catarrhalis (10%) Strept.pyogenes (3%), Staph aureus
(2%) and (28%) show no pathogenic growth. (5)
A prospective study was conducted by Pichichero ME.et al
(1995) in department of Pediatrics University of Rochester Medical
Center NY, USA. To determine the pathogens isolated from middle
ear fluids of 200 specimens in 137 children with persistence AOM
(which had not responded to empiric therapy) since October 1989Sept.1992 No bacterial growth in (49%), Strept.pneumoniae (24%),
Haemophilus influenzae (7%). Moraxella catarrhalis (7%), Strept.pyogenes
28
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(6%), Staph aureus (5%). Penicillin resistant isolates were (38%) of
Sterpt. pneumoniae isolates Thirty eight percent of Haemophilus
influenzae and all Moraxella catarrhalis produced beta-lactamases. For
comparison tympanocentesis from previously untreated AOM
patients, (30%) showed no bacterial growth. Strept.pneumoniae (36%),
from them (8%) were Penicillin resistant. Haemophilus influenza in
(13%), (44% were producing beta-lactamase), Moraxella catarrhalis
(11%),
(83% were producing beta-lactamase). AOM witch was
persistent after initial empiric therapy may be caused by middle ear
inflammation or involve penicillin resistant Strept. pneumoniae, betalactamase-producing Haemophilus influenza or Moraxella catarrhalis.
More common than it occurs in AOM which had not been recently
treated. (27)
Bacteria were isolated and cultured from ears of patients of
chronic suppurative OM who attended the otologic clinic of Kyusha
university hospital from 1976-1991, Staph aureus and Psuedomonas sp.
were the most common organisms. The incidence of Staph aureus
increased gradually over 16 years while Psuedomonas sp. gradually
decreases. (28)
29
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Another
study
showed
that
Streptococcus
pneumoniae,
Haemophilus influenzae and Moraxella catarrhalis are the most
common micro organisms in AOM. The incidence of Streptococcus
pneumonia peaked by age of 12 months where as Moraxella catarrhalis
at 6 months and Haemophilus influenzae at 20 months of age.
Strept.pneumoniae relation with seasons was lesser than the other
two. H. influenzae rarely caused the first two AOM episodes, but
became increasingly common after the third episode.(29)
The American Family Physicians and American Academy of
Pediatrics in its Clinical practice guideline (2004) stated that
organisms isolated in AOM are Strept.pneumoniae in (40-50%) of
cases then Haemophilus influenzaein (30-40%), Moraxella catarrhalis in
(10-15%) then followed by Group A streptococcus, Staph. aureus,
Gram-negative bacilli in newborns, immunosuppressed patients and
those with CSOM. Viruses in less than (10%) and No bacterial
pathogen in (20-30%) of cases.(1)Regarding Chronic suppurative
otitis media Aerobic organisms were commoner like Psuedomonas sp,
Proteus mirabilis,S.aureus, E.coli, or Klebsiella sp. Then anaerobic
bacteria like Bacteroides, Peptostreptococcus or propionibacte.
30
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1.2. OBJECTIVES
1.2.1. General Objective:
• To determine the causative organisms of Otitis media
among Sudanese patients seen in E.N.T Hospital,
Khartoum.
• To give a guideline in the empiric antimicrobial
management of both acute and chronic otitis media.
1.2.2. Specific Objectives:
• To isolate organisms causing both acute and chronic
otitis media.
• To establish the correlation between the type of
organisms and age groups.
• To determine the antimicrobial sensitivity pattern of the
causative organisms.
31
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2. PATIENTS AND METHODS
2.1. Study design:
This is a descriptive prospective cross-sectional hospital
based study.
2.2. Study period:
The study was conducted in the period from December 2008
to March 2009.
2.3. Study Area:
The Ear, Nose and Throat (ENT) Hospital. The Out-Patients
Clinic, in Khartoum State.
2.4. Study population:
Patients presented to the out-patients clinic in Khartoum ENT
Hospital suffering from otitis media with ear discharge, of different
age groups from both sexes were randomly selected. The required
data were collected through a questionnaire after verbal consent
from patients or their relatives.
2.5. Sample size:
According to the annual incidence and the confidence level,
the sample size was calculated, 104 clinical specimens (Ear swabs)
32
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were collected, from patients complaining of otitis media with ear
discharge.
2.6. Site of collection:
The specimens were collected from patients suffering from
Otitis Media with ear discharge, Samples collected with a sterile
cotton wool swab aided by good light source. Swabs delivered to
the laboratory within 2 hours to be processed.
2.7. Culture:
2.7.1. Inoculation:
Under aseptic conditions near Bunsen burner the specimens
were inoculated on to blood agar, chocolate (heated blood) agar and
MacConkey agar plates.
2.7.2.1ncubation:
The inoculated plates were incubated at 37c for 24 hours, one
of the blood agar plates were incubated under 5-10%CO2.
2.7.3. Examination of growth:
1- Colonial morphology: The primary cultures on the blood,
chocolate and MacConkey agar that showed heavy pure
growth were examined for fermentation on MacConkey agar,
haemolysis on blood and chocolate agar. The morphological
33
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character, size, shape, colour, pigment production and
haemolysis were studied. The resultant growth was
processed
for
biochemical
tests
and
antimicrobial
susceptibility testing.
2- Gram stain (appendix).
3- Biochemical tests (appendix).
2.7.4. Antibiotics susceptibility testing:
The suscebililty test was performed using Kirby-Bouer disk
diffusion technique.
Several colonies of the test organism were
transferred to 2 ml sterile saline using a sterile loop. The inoculum
turbidity was adjusted to MacFarland No.1 standard turbidity.
Suspension of the standard control strains was prepared and
processed the same as the tested organisms so as to assess the
validity of antibiotics, media and other variables.
2.7.6. Inoculation of Mueller-Hinton Agar:
The plates were inoculated by dipping a sterile cotton swabs
into the inoculum (tests and controls). Then the swab were streaked
over the Mueller-Hinton surface of the medium. All Streptoccoci sp.
Blood agar was used for antimicrobial susceptibility.
34
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2.7.7. Antimicrobial Disc Application:
Using sterile forceps, antimicrobial discs were placed at least
24 mm apart on the inoculated plates (9 cm plate).
Incubation: The plates were incubated at 37 °C for 24 hours. The
chocolate plates were incubated under CO2.
2.7.8. Reading and Interpretation:
The diameter of each zone of inhibition (including diameter
of the disc) was measured using a ruler, and interpreted according
to table 2 of NCCLS for test organisms and table 3 of NCCLS for
standard strains.
2.8. Data analysis:
Data was entered, checked and analyzed using SPSS software
Program.
35
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3. RESULTS
One hundred and four specimens were collected from patients
attending, Ear Nose and Throat Hospital (ENT) out-patient clinic.
In this study males comprised (60.2%) and females were
(39.8%).Regarding age groups, they are shown in (Table1).Type of
isolates are shown in (Table 2). In the study, patients with acute
otitis media comprised (41.7%), while those with chronic otitis
media were (58.3%), as shown in (Fig. 1).
The isolated organisms are listed in (Table 3).
There was an association between type of infection and age, AOM
decreases with age, while CSOM increases with age (Fig. 2).Also an
association between the organism isolated and the type of infection,
AOM mainly caused by S.pneumoniae, Staph.aureus and S.pyogen,
while ChOM mainly by Proteus sp., Psuedomonas sp., E.coli and
Klebsiella sp.(Fig. 3).Staph. aureus sensitivity pattern are shown in
(Fig. 4), S.pneumoniae (Fig. 5), S.pyogen (Fig. 6), Proteus sp. (Fig. 7),
Psuedomonas sp. (Fig. 8), E.coli (Fig. 9) and Klebsiella sp. sensitivity
are in (Fig. 10).
36
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Table 1: Distribution of patients according to age groups
Age group (in years)
Otitis media
Total (%)
Acute
Chronic
<1
18 (82.0)
4 (18.0)
22 (20.4)
1 - 15
29 (58.0)
21 (42.0)
50 (46.3)
16 - 30
3 ( 17.0)
15 (83.0)
18 (16.7)
31 - 45
2 (20.0)
8 (80.0)
10 (9.3)
46 - 60
1 (50.0)
1 (50.0)
2 (1.8)
-
6 (100)
6 (5.5)
53 (49.0)
55 (51.0)
108 (100)
> 60
Total
Table 2: Number and percentage of bacterial isolates
Isolates
Frequency
Percentage
Bacterial isolates
9
64
Fungal isolates
7
6.5
No growth
28
26
Non-pathogenic
4
3.7
108
100
isolates
Total
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Table 3: List of organisms isolated
Organism isolated
Frequency
Percentage
Staph. aureus
21
27.6
S.pneumoniae
18.5
S. pyogenes
.5
Pseudomonas sp.
11
14.5
Proteus sp.
18.5
E. coli
3
3.9
Klebsiella spp.
1
1.3
Fungi
9.2
Total
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Figure (1): Types of otitis media (n = 104)
49%
51%
Acute otitis media
Chronic otitis media
39
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Figure (2): Relation between age and types of otitis media (n = 104)
29
30
25
21
20
18
15
15
10
8
6
4
5
3
2
1
1
0
0
< 1YR
1-15 YRS
16-30 YRS
31-45 YRS
ACUTE OTITIS MEDIA
46-60 YRS
> 60 YRS
CHRONIC OTITIS MEDIA
40
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Figure (3): Relation between organisms isolated and
types of otitis media (n = 104)
14
13
12
12
12
10
11
9
8
7
6
4
3
2
3
2
2
1
1
0
0
eus oniae yogen s spp s spp
r
u
na roteu
ha
um ept.p
a
p
e
a
m
n
P
p
St
Str
udo
pt.
e
e
s
r
P
St
ACUTE OTITIS MEDIA
0
0
i
col
spp ection
.
a
E
l
l
f
e
l in
bsi
a
e
g
l
n
K
Fu
CHRONIC OTITIS MEDIA
41
0
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Figure (4): Susceptibility of Staph. Aureus
20
19
19
18
18
16
16
14
14
13
12
11
11
10
10
8
8
6
5
4
3
2
2
2
2
0
0
3
0
2
0
PE
NIC
ILL
IN
OX
AC
ILL
ER
IN
YT
HR
OM
YC
CO
IN
-A
MO
XY
CA
LV
E
CE
PH
AL
EX
IN
CE
FIX
IM
E
GE
NT
CH
AM
LO
ICI
RA
N
MP
HE
NI
CO
L
0
5
5
SEN
RES.
42
INTER
0
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Figure (5): Susceptibility of Strept. Pneumoniae
14
13
13
13
12
12
11
10
8
6
4
3
2
2
1
1
PE
NI
CI
LL
IN
OX
AC
ILL
IN
ER
YT
HR
OM
YC
CO
IN
-AM
OX
YC
AL
VE
CE
PH
AL
EX
IN
0
SEN
43
RES
1
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Figure (6): Susceptibility of Strept. pyogenes
5
5
5
4.5
4
4
4
4
4
3.5
3
3
2.5
2
2
1.5
1
1
1
1
0.5
0
0
PE
NI
CIL
LI
OX N
AC
ER
ILL
YT
HR IN
CO OM
-AM YCI
OX N
YC
A
CE LVE
PH
AL
E
GE XIN
N
CH
LO TAM
RA
ICI
N
MP
HE
NIC
OL
0
SEN
44
RES
1
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Figure (7): Susceptibility of Proteus spp
10
10
9
9
8
8
8
7
6
6
5
5
5
5
4
4
33
3
3
3 3
22
2
2
3
1
GE
NT
CH
AM
LO
ICI
RA
N
MP
HE
NIC
OL
CE
FT
RIA
XO
CI
ME
PR
OF
LO
XA
CIN
CE
FO
TA
XIM
E
CE
FU
RO
XIM
E
0
SEN
RES
45
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Figure (8): Susceptibility of Pseudomonas spp.
9
9
8
7
7
6
6
5
5
5
4
3
3
3
2
2
1
1
1
1
0
0
CEFOTAXIME
CEFTAZIDIME
AMIKACIN
SEN
RES
46
CARBINCILLIN
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Figure (9): Susceptibility of E. coli
3
3
2.5
2
2
2
2
2
1.5
1
1
1
1
1
0.5
0
CH
LO
RA
MP
HE
NIC
OL
CE
FT
RIA
XO
ME
CIP
RO
FL
OX
AC
IN
CE
FO
TA
XIM
E
CE
FU
RO
XIM
E
0
SEN
47
RES
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Figure (10): Susceptibility of Klebsiella spp.
1
1
1
1
1
1
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0
0
0
0
G
CH ENT
AM
LO
ICI
RA
N
MP
HE
NIC
CE
OL
FT
RI
CIP AXO
ME
RO
FL
OX
AC
CE
IN
FO
TA
XIM
CE
FU E
RO
XIM
E
0
SEN
48
INTER
0
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4. DISCUSSION
This study was done to determine the common bacterial
pathogens causing Otitis Media, in Sudanese patients and its
distribution according to age and sex, and the pattern of
antimicrobial resistance of bacterial isolates.
Regarding distribution among age groups the study showed
that children below fifteen years were 66%of the studied population
, this result was in agreement with Scott-brown`s (1997 )who stated
that otitis media is more common
in children because their
Eustachian tube is shorter, narrower and more horizontal than
adults.(30)
Regarding sex distribution males were 60.2%, while females
were 39.8%. This result is consistent with what is documented in the
Clinical Practice guideline of the American Academy of Pediatrics
(2004) which stated that Male sex had slightly increased incidence.
Regarding the distribution of acute and chronic otitis media
among patients, 49% were diagnosed as AOM, while 51% as CSOM.
In children below 15 years there is high incidence of CSOM (37.5%)
which is different from that written in the literature. Most of these
children came from areas outside Khartoum state of low
49
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socioeconomic status, ignorance and illiteracy. Most of them did not
receive any medications or incomplete courses of drugs. Some of
them came with complications e.g. hearing problems (three
children), low school performance (four), and Otitis externa in one
child.
In this study, 64% of the cultured ear samples yielded bacterial
isolates, fungal isolates were 6.5% and 28% showed no growth of
pathogens. These results were consistent with those obtained by M.
Bilal (2002) from Sudan that showed 76%bacterial isolates, 4%
fungal isolates and the remaining 19% revealed no growth of
pathogens.
From this study there was a correlation between age groups
and the type of infection. In children less than 15 year 62.5%
diagnosed as having AOM, while 37.5% had CSOM. Eighty percent
of patients in the age group 31-45 years diagnosed as CSOM. In the
last age group (over 60 years) only chronic otitis media was their.
From these results it was clear that acute otitis media decreased with
age, while chronic otitis media increased with age.
The causative organisms for otitis media as general (acute and
chronic) in this study were Staph.aureus followed by, St. pneumoniae,
50
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Proteus sp. and Psuedomonas sp. .These results were in agreement
with the local study conducted by M. Bilal (2002) where Staph.sp
were the main causative organism followed by Streptococcus sp
,Proteus sp and Psuedomonas sp.
Regarding the bacterial causes of Acute Otitis Media (AOM) in
this study, 50% were due to St. pneumoniae, 38% due to Staph.aureus,
and 12% were due to St.pyogenes , in comparison to what was
obtained by Eiad A (2001) in King Abdul-Aziz University
Streptococcus pneumonia comprised 25%, Haemophilus influenzae
36.6%, St.pyogenes 20%, Staph. aureus 15% and Maroxella catarrhalis
1.6%.
Comparing with other international studies, in Sel.uk
University, Ankara (2002), among children of AOM, Streptococcus
pneumoniae 39%, Haemophilus influenzae 27%, Maroxella catarrhalis
10%, St.pyogenes 3% and Staph aureus 2%.
Also a study in University of Rochester Medical Centre New
York (1995) to determine the causative organisms of persistent AOM
Streptococcus pneumoniae 24%, Haemophilus influenzae 7%, Maroxella
catarrhalis 7%, St.pyogenes 6%, Staph aureus 5%.
51
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From all of these results we observe that higher incidence of
Staph aureus in this study and other local Sudanese studies as a
causative organism of AOM and also the absence of both
Haemophilus influenzae and Maroxella catarrhalis. These significant
differences might be due to environmental factors, or technical
errors, e.g. the absence of the transport media which might affect the
growth of these fastidious organisms, also the absence of standard
organisms from these strains.
The bacterial causes of CSOM in this study showed that
Proteus sp. were 33%, While Staph.aureus comprised 30% and 27.5%
were due to Psuedomonas sp. Comparing to another study regarding
bacterial causes of chronic otitis media done by Attallah MS (2000)
in King Abdul-Aziz University Hospital revealed that Pseudomonas
sp. were 51%, Staph aureus 31% and Proteus sp.17%. Another study
conducted in children Hospital in Addis Ababa (1999) among
CSOM. Showed that Proteus sp. were 37.7% followed by Staph aureus
and Psuedomonas sp. Both studies showed the same causative
organisms of our study but of different percentages.
52
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Regarding the pattern of antimicrobial sensitivity, 90% of
Staph.aureus isolates were Penicillin resistant, 10% Methacillin
resistant (MRSA), while M. Bilal found that most Staph.aureus strains
were resistant to both penicillin. Eiad (2001) at King Abdul-Aziz
University Hospital found that, 51% of Staph.aureus isolates were
Penicillin resistant, 6.7% were Methacillin resistant isolates.
Streptococcus pneumoniae isolates were 79% sensitive to
penicillin in this study. While, Eiad A. (2001) at In King Abdul-Aziz
University Hospital stated that 64% of St. pneumoniae isolates were
sensitive to penicillin. In the study conducted by Pichichero ME.
et al (1995) in Rochesrer Medical Centre NY, isolated St. pneumoniae
from patient of persistent AOM were (72%) sensitive to penicillin
unlike those of AOM not previously treated show (92%) penicillin
sensitivity.
Psuedomonas aeruginosa isolates were 82% sensitive to
Ceftazedime, its sensitivity to Cefotaxime was 64%. These results
were agreed by a local study conducted by Amena A. (2006) where
91% of Psuedomonas sp. isolates were sensitive to ceftazidime and
cefotaxime sensitivity was 54%.
53
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From all the obtained results we notice increasing resistance of
Staph.aureus isolates to penicillin and the percentages of MRSA. Also
increasing resistance of St. pneumoniae isolates to penicillin, and of
Psuedomonas aeruginosa to ceftazidime.
This rising resistance of microorganisms to the commonly
used drugs is mainly due to the misuse of antibiotics, prescribing
without strong base, e.g. for viral infections and the ease of issuing
any antibiotic over the counter without doctor prescription, also,
due to patient non-compliance.
54
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4.1. CONCLUSION
The study concluded that:
Among patient complaining of otitis media, males were
65 (60.2%), while females 43 (39.8%).
Children below fifteen years comprised (66.7%), from all other
age groups.
Acute otitis media decreases with age, while chronic otitis
media increases.
Streptococcus pneumoniae is the main causative organism for
AOM followed by Staphylococcus aureus, then Strept.pyogen.
Proteus sp was the main causative organism of chronic otitis
media, followed by Staph.aureus, then Psuedomonas spp., E.coli and
lastly Klebsiella spp.
S.pneumoniae strains were (79%) sensitive to Penicillin, (93%)
sensitive to both Co-amoxycalve and Cefalexin and (86%) to
Erythromycin.
Staph.aureus strains were (90%) Penicillin resistant, (85%)
sensitive to Cefixime, Chloramphenicol and Gentamicin sensitivity
55
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were (76% & 52%) respectively, Cefalexin (67%) and Co-amoxycalve
sensitivity was (52%).
Psuedomonas spp. isolates were highly sensitive to Ceftazidime
(82%), followed by Carbencillin (73%), Amikacin (55%) and
Cefotaxime (64%).
Proteus spp. (86%) were sensitive to both Cefotaxime and
Ceftriaxone, (79%) to Ciprofloxacin and (79%) to Gentamicin, (71%)
to Chloramphenicol and (64%) to Cefuroxime.
56
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4.2. RECOMMENDATIONS
Otitis Media is one of the common diseases especially in
childhood, it had great influence on work and school attendance
and it may lead to hearing loss if not properly diagnosed and
treated. So we recommend that:
• Proper diagnosis and treatment, any patient complaining of otitis
media ear swab have to be taken, so as to continue with or to
change the empirical treatment.
• More studies have to be done to isolate Haemophilus influenzae
and Moraxella catrrhalis as causative organisms of otitis media.
• Early diagnosis and treatment of otitis media, so as to reduce
complications, especially in children.
• To establish adequate microbiology service in the major hospitals
for accurate diagnosis and to determine the antimicrobial
susceptibility patterns and to establish a surveillance system for
antimicrobial resistance.
57
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REFERENCES
1. Muhammad WS, Muhammad AS. Otitis media: Diagnosis and
management of acute otitis media eMedicine, July 22, 2008.
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CD,
Rosenfeld
RM.
Otitis
Media;
Definitions,
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Acute Otitis Media in children. Journal of
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10. Rachel E. Hardisty, et al. Causes of otitis media in the Jeff
mouse. Oxford Journals, Human Molecular Genetics 2006 Oct.;
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11. Allan SL, Theodore GG, Edward OC. American Academy of
Family Physicians, American Academy of Otolaryngology-Head
and
Neck
Surgery,
American
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effusion. Pediatrics J 2004; 113: 1412-2.
12. Rosenfeld RM, Vertrees JE, Carr J, et al. Clinical efficacy of
antimicrobial drugs for acute otitis media: Metaanalysis of 5400
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355-67.
13. Kaleida PH, Stool SE. Assessment of otoscopists’ accuracy
regarding middle-ear effusion. Am J Dis Child 1992; 146: 433-435.
14. Block SL, et al. Gradient acoustic reflectometry for the detection
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Infect Dis J 1998; 17: 560-564.
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Improvement diagnostic accuracy. Am Fam Physician 2000
April; 61: 2051 – 6.
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16. Carlin SA, Morchant CD, Shurin PA. Host factors and early
therapeutic response in acute otitis media. J Pediatr 1991; 118:
178-83.
17. Janak AP, et al. Role of respiratory syncytial virus in acute otitis
media: implications for vaccine development. PMC 2007 March;
25(9): 1683 – 89.
18. Michael E, Pichichero MD. Acute otitis media Part II. Treatment
in the era of increasing antibiotic resistance. Am Fam Physician
2000 April; 61: 2410-6.
19. Arrieta A, Singh J. Management of recurrent and persistent
acute otitis media: new options with familiar antibiotics. Pediatr
Infect Dis J 2004; 23 (2 suppl): S115-24.
20. Perera R, Haynes J, Glasziou P, Heneghan CJ. Autoinflation for
hearing loss associated with otitis media with effusion. Cochrane
Database Syst Rev 2006; (4): CD006285.
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Family Physicians. Clinical practice guideline. Diagnostics and
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23. Mouhammed BI. Microbial causes of otitis media in Sudanese
patients, Thesis for Msc, Sudan University, 2002.
24. Attallah MS. Microbiology of chronic suppurative otitis media.
Saudi Med J 1985; 21: 924-927.
25. Eiad A, Hamza A, Gulam J, et al. Microbiology and Sensitivity
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26. Melako L. Chronic suppurative otitis media in children. Ethiopia.
Ethiopia Med J 1999; 37: 237-46.
27. Pichichero ME, Pichichero CL.Persistent acute otitis media.
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28. Nicro N, Controlled multicenter study on chronic suppurative
Otitis Media. Otolaryngol Head-Neck Surgery 2000; 123: 617-623.
29. Kilpi T, Herva E, Kaijalainen T, Syrjanen R, Takala AK.
Bacteriology of acute otitis media in a cohort of Finnish children
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30. Scott B. Scott-Brown’s Otolaryngology, 6th edition. 1997.
P. 316 -317.
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Appendix (1)
Ϣ
ϴ
Σή
ϟ
΍
ϦϤ
Σή
ϟ
΍
Ϳ΍
Ϣ
δΑ
University of Khartoum
The Graduate College
Medical and Health Studies Board
Questionnaire
Bacterial causes of Otitis Media in Sudanese patients seen in the E.N.T
Hospital in Khartoum
Date: ....................................................................
Serial No: ...........................................................
Lab. No.: .................................................................
Name: ....................................................................
Age: ...........................................................................
Residence: .........................................................
Gender:
Symptoms:
- Male
(
)
- Female
(
)
- Ear pain (
)
- Ear discharge
(
) - Colour: .........................
(
)
- Itching (
) - Hearing loss
Duration of symptoms: ………………………………………………………………………………
Diagnosis:
- AOM
(
)
- CSOM (
)
Antimicrobial used: ……………………………………………………………………………………..…
Laboratory findings: ………………………………………………………………………………………….
Morphology: ..........................................................................................................................................................
Microscopy: ...............................................................................................................................................................
Organism isolated: .............................................................................................................................................
Antimicrobial susceptibility:
.............................................................................................................................................................................................................
............................................................................................................................................................................................................
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Appendix (2)
I) Reagents:
1- Oxidase Reagent
This is Tetramethyl p-phenylemediamine dihydrochloride
obtained from BDH chemicals Ltd, Pool, England as powder and
prepared according to cheesborugh (1985).
2- Kovacs Reagent:
This is dimethyl amino benzaldehyde obtained from BDH
chemicals Ltd and prepared according to cheeshbrough (1985)
3- Sodium chloride (Normal saline ‘0.85% w/v’).
Oxoid Ltd,
England. Prepared according to Cheesbrough (1985).
4- MacFarland standard:
(Dihydrate barium chloride 1.175% w/v + sulphuric acid 1%
v/v). Obtained from BDH chemicals Ltd, Poole England and
prepared according to Cheesbrough (1985).
5- Hydrogen peroxide
3% 2.8.6 plasma.
II) Standard strains:
Staphylococcus aureus, ATCC.
Pseudomonas aeruginosa, ATCC 27853, USA.
Escherichia coli, ATCC.
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Antimicrobial Discs:
The following antimicrobial discs used in the research:
1. Penicillin G (P)
10 IU. oxoid, UK
2. Oxacillin (OX)
1 mg. oxoid,UK
4. Coamoxycalve(Au)
20/10 mg. oxoid, UK
5. Cefalexin.(CL)
30 mg. oxoid, UK
6. Cefixime.(CFX)
5mg, Bioanalyse, UK
7. Cefuroxime.(CU)
30 mg, Bioanalyse, UK
8. Cefotaxime (CTX)
30 mg, Abtek Biological Ltd, UK
9. Ceftriaxone (CRO)
30 mg Bioanalyse, UK
10. Ceftazidime (CAZ)
30 mg, Abtek Biological Ltd., UK
11.Gentamicin.(Gen)
30 mg, oxoid,UK
12.Amikacin.(AK)
10 mg, oxoid, UK
13.Chloramphenocol.(C)
30 mg, oxoid, UK
14.Carbincillin.(CAR)
100 mg, Bioanalyse, UK
15.Ciprofloxacin (CIP)
5 mg, oxoid , UK
16. Bacitracin(B)
10IU, oxoid , UK
17. Optochin (Opt)
0.3 IU, oxoid , UK
18.Erythromycin(E)
15mg oxoid , UK
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III) Stains:
Aset of Gram Stain:
Crystal violet, Lugol iodine, Ethanol 95% and Safranine were
Obtained from Sigma company, England and prepared according to
Cheesebrough (1985).
Procedure:
This used to differentiate the bacteria into Gram positive and
Gram negative. During examination of smears bacterial shapes and
arrangements were studied, the technique was done as follows:
1. A portion of colony was emulsified in a drop of normal saline
in clean slides and then spread evenly to prepare thin smear.
2. The smear was fixed by gentle heat and covered with crystal
violet for one minute, then washed rapidly with clean water.
3. Lugol iodine was added for one minute and washed with clean
water.
4. Alcohol was added for few seconds and washed rapidly by
clean water.
5. The smear was covered with safranine (counter stain) for two
minutes and then washed with clean water.
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6. The smear was examined microscopically, after air drying,
using oil immersion lens. The results were reported.
IV) Biochemical tests:
a) Catalase test:
The test was done to differentiate bacteria that produce
catalase enzyme which break down of H2O2 to oxygen and water.
The test was done by inoculating bacteria under test using wood
stick in a test tube contains 2 ml of 3% H2O2. The result observed
immediately. Active bubbling indicates positive test (Cheesbrough,
2000).
b) Coagulase test:
The test used to differentiate bacteria that produce the
enzyme coagulase from which does not prouce it. Coagulase cause
plasma to clot by converting the fibrinogen to fibrin.
The test was done by emulsifying bacteria under test in a
drop of physiological saline in slide. A drop of plasma was added
and mixed gently. Clumping to the organism observed within 10
seconds as positive test.
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c) Oxidase test:
This test was done by smearing a portion of colony using
wooden stick on filter paper impregnated in oxidase reagent.
Phenylene diamine in the reagent will be oxidized to Purple colour
appeared within 10 seconds indicating positive for oxidase test
(Cheesbrough, 2000).
d) Indole production:
The test used to identify enterobacteriaceae that break down
amino acid tryptophane with release of indole. The test was done by
inoculating peptone water with bacteria under test. Then incubated
at 37 °C for 24 hours.
The indole formations were detected by adding Kovacs
reagent. The result observed by presence of pink ring (Cheesbrough,
2000).
e) Urease test:
Test used to identify some bacteria that produce urease
enzyme which break down the urea (2NH2CONH2) into ammonia
(NH3) and CO2. The test was done by inoculating urea agar with
test organism and incubated at 37 °C for 24 hours. The change in the
colour to pink colour indicates positive test (Cheesbrough, 2000).
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f) Citrate utilization:
The based on the ability of bacteria to use citrate as it is only
source of carbon and ammonium salt as source of nitrogen. cimmon
citrate agar was inoculated with organism under test then incubated
at 37 °C for up to 4 days and checked daily. Bluing of the media
indicates positive test for citrate utilization.
i) Fermentation of sugars, production of gas and acid:
The test based on the ability of bacteria to ferment sugar
(lactose and glucose) and production of gas and H2S, under aseptic
conditions. KIA was inoculated with the organism under test by
using straight wire. Then incubated at 37°C for overnight. Then
change in colour crack and production of H2S was observed
(Cheesbrough, 2000).
68