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Indian Academy of Pediatrics

IAP Vision 2007

IAP Vision 2007


Problem Solving in
Pediatric Infectious Diseases
(PSPID)

Greetings
from
IAP Executive Board 2007

IAP : Office Bearers 2007


President
President Elect
Imm. Past President
Vice President
Secretary General
Treasurer
Jt. Secretary
Editor IP
Editor IJPP
AAA

:
:
:
:
:
:
:
:
:
:

Dr Naveen Thacker
Dr R K Agarwal
Dr Nitin K Shah
Dr Ajay Ganbhir
Dr Deepak Ugra
Dr Rohit Agrawal
Dr Gadadhar Sarangi
Dr Panna Choudhury
Dr A Balachandran
Dr Kamlesh Srivastava
4

IAP : Executive Members 2007


DR ABHINANDAN DAS
DR AJAY KALRA
DR ANIL SUD
DR ANUPAM SACHDEVA
DR ARUN KUMAR
DR ARUN KUMAR MANGLIK
DR ARVIND GUPTA
DR ASHOK KUMAR RAI
DR D VIJAYASEKARAN
DR DIGANT D SHASTRI
DR GA MANJUNATH
DR GAUTAM GHOSH

IAP : Executive Members 2007


DR GUHAN BALRAJ
DR HARISH KUMAR PEMDE
DR HARSHAD K TAKVANI
DR JAI B BANSAL
DR JAYAKUMAR C PANICKER
DR K NEDUNCHELIAN
DR KAVINDRA SARBHAI
DR KSH CHOURJIT SINGH
DR M VASUDEVA MURALI
DR ML AGNIHOTRI
DR NAVEEN BENAKAPPA
6

IAP : Executive Members 2007


DR PNN PISHARODY
DR PRADEEP K GUPTA
DR PRADEEP KUMAR KAR
DR RAJENDRA V KULKARNI
DR RAJENDRA Z GANDHI
DR RAJESHWAR DAYAL
DR RAJKISHOR B MAHESHWARI
DR S BALASUBRAMANIAN
DR S SANJAY
DR SA KRISHNA
DR SATISH K TIWARI
DR SHARAD THORA

IAP : Executive Members 2007


DR SHRINATH B MUGALI
DR SUBHASH SINGH SLATHIA
DR SURESH C GOYAL
DR US JAGDISH CHANDRA
DR VS YAJURVEDI
DR YASHWANT PATIL

The concept of PSPID


Aims to rationalize diagnosis and management
of pediatric infectious diseases
Targets are common and/or serious infectious
diseases
Five modules are discussed as case based,
interactive sessions
Delegates participation is most important for the
success of implications of these modules
9

The Team : PSPID


President IAP 2007

: Dr Naveen Thacker

Hony Sec Gen IAP

: Dr Deepak Ugra

National Convener

: Dr Tapan Kumar Ghosh

Co Convener

: Dr Baldev Prajapati

Writing Committee

: Dr Tanu Singhal

Dr Suhas Prabhu
Dr Indu Khosla
10

Zonal coordinators
East : Dr Nupur Ganguly
North : Dr Shyam Kukreja
South : Dr S Balasubramanian
Central : Dr Rajeswar Dayal
West : Dr Digant Shastry &
Dr Kamlesh Srivastava

11

Contributors

(in alphabetical order)

Dr Rohit Agrawal
Dr Nupur Ganguly
Dr Tapan Kumar Ghosh
Dr Indu Khosla
Dr Ritabrata Kundu
Dr Baldev Prajapati
Dr Suhas Prabhu
Dr Tanu Singhal
Dr Vipin Vashishtha
Dr Vijay Yewale
12

Appeal from National Convener


There are 5 modules in this program
1. Child with fever and CNS symptoms
2. Child with fever and respiratory symptoms
3. Pneumococcal disease burden, MDR and prevention
4. Child with fever
5. Rational antimicrobial therapy

Total number of slides 157


Please do not change any slide of this module. All the slides are to be
discussed in chronological order following the module prepared by the
contributors and writing committee.
To see the speakers note please click Note Page under View Menu.
Dr Tapan Kr Ghosh
National Convener

13

Module 1
Febrile child with CNS manifestations

Case - 1

9 month old male


High fever for last 2 days
Irritability
Poor feeding with occasional vomiting

15

What are the possibilities?


Prodrome of a respiratory/ gastroinetestinal
infection
Bacteremia
Urinary tract infection
Pyogenic Meningitis

16

What will you do further ?


Ask for ?
Upper respiratory symptoms, otorrhea
Any antibiotics taken
Immunization history (Hib vaccine, pneumococcal vaccine)
Look for ?
Skin rash (especially purpura)
Fontanelle
Signs of meningeal irritation
Otoscopy
Relevant clinical examination

17

Case 1- History and examination

No otorrhea / URI symptoms


Has been on oral amoxi-clav
Not received Hib/ pneumococcal vaccine
No rash
Bulging fontanel
No neck stiffness, meningeal signs absent
No history of drugs that can cause bulging fontanel
Otoscopy ear wax
18

Provisional diagnosis
Pyogenic meningitis

What tests will you do ?

LP and CSF examination ASAP


Is a must and should be done before antibiotic
Examine CSF within 30 minutes of LP
CSF sugar in fluoride vial/ bulb
Send blood sugar just before LP

CBC, Blood cultures


20

Delay in LP
When should LP be delayed?

Hypotension, Shock
Severe respiratory distress
Signs of herniation such as unequal pupils
Papilloedema
Decerebration

What if LP is delayed?
Send blood cultures and start empirical Abx
CNS imaging if possible (Contrast CT is adequate)
21

What tests will you ask for in CSF?

Cytology
Sugar, Protein
Gram stain ( Sens 40-70%, Specificity 97%)
Latex agglutination for H flu, Meningococci,
Pneumococcus (Sens 70%)
CSF cultures (Sens 70-85% in antibiotic
nave)
22

What treatment pending reports ?


IV third generation cephalosporins (Ceftriaxone
100 mg/kg/day)
Supportive care
Steroids in this case ?

23

Steroids in childhood pyogenic


meningitis
Reduce morbidity in H flu, questionable efficacy in others
Start empirically in all antibiotic naive patients with
suspected pyogenic meningitis after LP is done
Should not be given if already on IV antibiotics, in
neonates and if LP cannot be done
Should be preferably given 10-20 minutes prior/ along
with first dose of Abx
0.15 mg/kg of dexamethasone 6 hrly for 48 hrs.
Stop earlier if pyogenic meningitis not confirmed on CSF
cells & biochemistry
24

Investigation results in our patient


CSF

Traumatic
40,000 RBC, 500 WBC, 60% polymorphs
RBC: WBC ratio is 80:1
CSF sugar 30 mg%, blood sugar 80 mg%
CSF protein 200 mg%
CSF Gram stain negative
Latex negative for H flu, S. pneumoniae, Meningococci
Culture awaited

TLC 18,000; 78% polymorphs


MP negative
25

What is your interpretation?


Partially treated pyogenic meningitis

26

CSF evaluation
Parameter (normal)

Pyogenic

Aseptic/
Viral

Partially
treated pyo
men

Early TBM

Cells (<5/ cumm)

10010,000,
Polys

10-1000
Lymphos

5-10,000
Lymphos>
polys

10-500, polys
early and then
lymphos

Sugar (40-60 mg%)

Low < 50%


of blood
glucose

N except
mumps

Low < 50% of


blood glucose

< 50%

Protein (20-40 mg%)

100-500
mg%

50-200 mg%

100-500 mg% 100-1000

Gram St & C/S

Positive

Neg

Usually Neg

Neg

ADA, Lactate, LDH

High

High

High

27

Interpretation of traumatic LP
Fairly common, especially in neonates
Interpretation is tricky
Usual ratio of RBC: WBC is > 500:1
Protein content increases by 1 mg% for 100 rbc
Sugar may be low

Repeat after 48 hours if required

28

How long will you treat for ?


Duration
Organism not identified - Antibiotics for 10-14
days, intravenous, no switch to oral
7 days for meningococcus, 10-14 days for H flu
and pneumococcus

Watch for complications- subdural effusion,


hydrocephalus (HC monitoring)

29

When will you repeat the LP ?


No need to repeat LP if diagnosis was certain
and clinical response is good
If no clinical improvement in 48-72 hours, repeat
LP, but also look for other causes of persistent
fever (CNS imaging should be done)
Definitely repeat LP before changing Abx

30

Management algorithm
Suspicion of pyogenic meningitis
Any contraindication to LP
No
Blood C/s, LP STAT
Abx + Steroids

Yes
Blood C/s, Empirical Abx,
CNS Imaging ( CT)

CSF findings consistent with meningitis No contraindication


to LP
Continue therapy
31
CSF

Case 2

5 year old male


Monsoon, rural West Bengal
Fever for 2 days
Excessive somnolence
Generalized seizure
Altered sensorium since then

32

What are diagnostic possibilities ?


Encephalitis

Japanese encephalitis
Herpes simplex encephalitis
Mycoplasma
Enterovirus
Other viruses varicella, mumps, measles, rabies,
dengue, chandipura
Acute disseminated encephalomyelitis (ADEM)

Cerebral malaria
Encephalopathy (Reyes syndrome, metabolic
encephalopathy, epileptic encephalopathy)
Rarely pyogenic meningitis, TBM
33

What will you ask for ?

Concurrent cases in neighbourhood


H/o exanthematous illness
Aspirin/ drug intake
Animal bites
H/o upper respiratory illness, vaccination

34

What will you look for ?

Pallor, icterus, hepatosplenomegaly


Skin rash
Respiratory signs
Meningeal signs, fundus evaluation
Symmetrical or asymmetrical neurologic signs
Involuntary movements

35

History & PE in our case..

Negative history
No pallor, icterus, organomegaly
No skin rash
No respiratory signs
Left sided hemiparesis
No abnormal movements, no meningeal
signs
36

What is the likely diagnosis ?


Encephalitis
HSV
JE
ADEM

37

What investigations would you ask for?

CBC
PS for MP
Rapid malaria antigen tests?
SGPT, BS, creatinine, electrolytes
CXR
CSF unless contraindicated
cytology, sugar, protein, gram stain & C/S

Contrast enhanced MRI preferred


Contrast CT if MRI not available
EEG
38

What treatment pending reports ?

ABC of resuscitation
Supportive care
Anticonvulsants
IV Acyclovir 10 mg/kg 8 hourly
IV azithromycin 10 mg/kg for mycoplasma
IV antimalarials not required
IV ceftriaxone ?
No empirical steroids
39

Investigation results
Hb 11.0, TLC 7000, P 50 L 40 M5 E5, platelet
count 2,00,000
MP negative, Malaria antigen negative
SGPT 34, BS 76
CXR NAD
CSF: 70 WBC, 90% lymphos, 10 RBC, Sugar
64, Protein 100 mg% , Gram stain negative
40

Imaging- Contrast MRI

Left temporal hyper intense lesions


41

Diagnosis
HSV encephalitis

Differential diagnosis
Paramet
er

Viral E

Mycopla
sma

ADEM

Cerebral
malaria

CBC

Normal

Normal

Normal Low Hb, low Normal


platelets,
MP

Blood
sugar

Normal

Normal

Normal May be low

Markedly
low

SGPT

May be
elevated

May be
elevated

Normal Mild
elevation

Markedly
elevated

CXR

Normal

Infiltrates

Normal Usually
normal

Normal

Contrast
MRI

Abnormal Normal or Abnor


non
mal
specific

Normal/
Cerebral
edema/
infarcts

Reyes
syndrom
e

Cerebral
edema
43

MRI

JE

ADEM
44

Differential diagnosis- CSF


Parameter

Viral E

Mycoplas
ma

ADEM

CSF

Usually
abnormal

50%
normal

Usually
Usually normal Normal
abnormal

Cells

50-1000
Mononucle
ar
RBC in
HSV

Few
Mononucle
ar cells

No cells/
few cells

Usually less
than 10 cells,
rarely upto 50

No cells

Sugar as
compared
to BS

Normal
Normal
Mumps
may be low

Normal

Normal or low

Normal

50-100

May be
Normal
elevated ( upto
200 mg%)

Protein (mg 50-200


%)

10-100

Cerebral
malaria

Reyes
syndrome

45

Algorithm for management


Acute fever, seizures, altered sensorium
1. Resuscitation
2. Clinical examination
3. CBC, MP, BS, SGPT,BS, Na, K, Creat, CXR,
CSF
4. Supportive care, anticonvulsants, IV Acyclovir,
IV macrolide, + IV artesunate + IV ceftriaxone
5. MRI brain, EEG if available, repeat MP
Definitive diagnosis made
Continue specific therapy,
omit others

No definitive diagnosis
Continue acyclovir, macrolide
Omit Abx if pyomen ruled out
Omit antimalarials
46
if repeat smears negative

Module 2
Child with Fever and Respiratory
Symptoms

Case
5 yr male
Fever and cough since 3 days
Difficulty in breathing for 1 day

48

What will you ask for ?

Sneezing/ coryza
Nature of cough
Feeding and activity
History of immunization (Hib, Pneumococcal)
History of antibiotic use, day care and
hospitalization
History of pyoderma/ measles
Previous episodes of breathlessness
History of atopy and use of bronchodilators
Family history of atopy/asthma
49

What will you look for ?

Respiratory rate
Vitals, general appearance
SpO2 (If available)

Pallor and cyanosis


Signs of respiratory distress ( alae nasi flare,
grunt, stridor, retractions)
Detailed chest examination
50

In our patient..

1st Episode, no F/H/O Asthma/Atopy


Received Hib vaccine
Not feeding well, toxic appearance
No cyanosis
RR 50/min, alae nasi flare present, lower chest
retractions
Bronchial breathing + fine crepts + in LUZ
No murmur
51

What is your diagnosis ?


Severe pneumonia

What is tachypnoea ?
Age
< 2 months

Respiratory rate
(breaths/min)
60 or more

2 months upto 12 months

50 or more

12 months upto 5 years

40 or more

WHO recommends using these Respiratory rate cutoffs to


diagnose pneumonia at the community level
53

Causes of tachypnoea other than


pneumonia

Bronchiolitis
WALRI
Asthma
Metabolic acidosis (DKA, CRF)
Congestive Heart Failure

54

What investigations in this case?


CBC
CXR

55

Is a CXR required ?
All patients do not require a CXR to confirm
the diagnosis
Reliability in predicting the etiology is poor
However CXR is indicated when
Diagnosis is in doubt
No improvement/ worsening after 48-72 hours of
therapy
Complications suspected - empyema
56

Investigation results..
CBC: Hb 9.5, TLC 14,000, 70% polys
CXR

57

Lobar pneumonia

What tests to determine etiology ?


Blood Cultures
Sputum gram stain and culture
Serologic tests
Mycoplasma and Chlamydia
Pneumococcus (antigen detection in urine)
Viruses

59

Are these tests required ?


Not recommended routinely
Sample collection (sputum) is difficult and
invasive methods such as BAL and lung puncture
not justified routinely
Yield is poor (Blood C/S positivity 15%)
Serologic tests poor sensitivity/ specificity
Expensive and not easily available
Indicated only in immunocompromised, non
responding and nosocomial pneumonias
60

How will you manage this child ?


Inpatient Vs outpatient
Antibiotics

61

Indications for hospitalization


Respiratory rate > 70 /min, in infants
> 50/min in older children
Respiratory distress-grunting, alae nasi flare,
ICR or SCR
Cyanosis OR SpO2 < 92% in room air
Poor oral intake
Inappropriate observation or supervision
at home
62

Which antibiotics for pneumonia?


All pneumonias deserve antibiotics as differentiation
between viral & bacterial difficult
As identification of causative bug usually not
possible choice of Abx is empirical but depends on

Age
Severity
Predisposing conditions if any
Local epidemiologic data on etiology and drug resistance

63

Age related pathogens in CAP


0 3 months

Gram Negative
Chlamydia trachomatis
Viruses
S. pyogenes

3 months- 5
years

Viruses (35%)
S. pneumoniae
H. influenzae
S. pyogenes
Mycoplasma pneumoniae

> 5 years

S. pneumoniae
Mycoplasma pneumoniae (24-30%)
Staphylococcus
Viruses
S. pyogenes

64

Clues to etiology of pneumonia


Predisposing
factor

Organism (apart from usual


ones)

Pyoderma, Measles Staphylococcus


HIV

Pneumocystis

Neutropenia

Gram negative, Aspergillus

Cystic fibrosis

Pseudomonas,
Staphylococcus
65

Clinical/ investigation clues for etiology


Preceding coryza- ? Viral
Young infant with neonatal conjunctivitis- ?
Chlamydia
Multisystem involvement (rash, anemia,
hepatitis, CNS) ? Mycoplasma
No leukocytosis viral/ mycoplasma
Pneumatoceles Staphylococcus
66

Antibiotics for outpatients


Age

First Line

Second line

3 months- 5
years

Amoxicillin*

Coamoxiclav/
Chloramphenicol

> 5 years

Amoxicillin*

Macrolide**/
coamoxyclav/
chloramphenicol

< 3 months treat as inpatients


* Standard doses 30-50 mg/kg/day
** Erythromycin/ Clarithromycin/ Azithromycin
67

Antibiotics (IV/IM) for inpatients


Age

First Line

Second line

< 3 months

Cefotaxime/ Ceftriaxone +/- aminogly

3 months- 5
years

Coamoxyclav OR
Amp + Chloro

Coamoxyclav/
Ceftriaxone/
Cefotaxime

> 5 years

Ampicillin/
Chloramphenicol/
Coamoxyclav/
Macrolide (if mycoplasma
suspected)

Coamoxiclav/
Ceftriaxone/
Cefotaxime
AND
Macrolides

Suspected
staph

Cefuroxime
Or co amoxiclav
Or IV 3rd gen ceph.+ clox

Ceftriaxone/
Cefotaxime AND
Vancomycin/teico/li
68
nezolid

In this case..
Etiology
Most likely Pneumococcal

Management
Hospitalization
IV Ampicillin (100- 200 mg/kg/day)

69

On the third hospital day


Fever persisting
No clinical improvement
What could be possibilities ?
Complication (empyema)
Resistant organism ?
Different organism ? mycoplasma
70

What will you do ?


Repeat CBC, CXR
USG chest
Tests for mycoplasma
Retic count
Cold agglutinin tests
Mycoplasma serology

71

Investigation results

CBC: Hb 8, TLC 13,000, platelets N


CXR : no change
USG chest: no fluid
Serology and other tests awaited

72

What will you do ?


Switch to second line therapy
Ceftriaxone (for possible resistance)
AND

Macrolide ( empirically for mycoplasma)


Azithromycin 10 mg/kg/ day OD for 3 days
OR
Clarithromycin 15 mg/kg/day BD for 14 days

73

Duration of therapy in pneumonia


Domiciliary 5-7 days
Inpatient - switch to oral after 48-72 hrs or
earlier if can accept orally. Total 5-7 days
If on second line then IV for 7-10 days
If staph 2 weeks at least if no complication else
4-6 weeks

74

Module 3
Pneumococcal Disease Burden,
Antimicrobial Resistance
and
Prevention

Case

20 month old boy


Well at home till 3 days ago
Working mother, child in day-care
Fever and progressively rapid breathing for 3 days
Chest X-ray and USG shows consolidation with
effusion
Thoracocentesis shows exudative fluid
Diagnosis - Empyema

76

What is the likely organism ?

Pneumococcus (S. pneumoniae)


H. influenzae
Staphylococcus
Other Streptococci

77

Pleural fluid gram stain

Lanceolate shaped diplococci

78

Diagnosis
Pneumococcal pneumonia with
empyema

Pneumococci and disease


S. pneumoniae are usually commensals in
the nasopharynx
Cause disease by spread to other sites
via bloodstream (Invasive Pneumococcal
Disease IPD) - Bacteremia/sepsis, meningitis,
bacteremic pneumonia, peritonitis, cellulitis, arthritis,
etc. (40-50% mortality)

by contiguous spread (Non-invasive) - Nonbacteremic pneumonia, acute otitis media, sinusitis


80

81

Pneumococcal Disease Spectrum


For each case of pneumococcal
meningitis in a year

Noninvasive

Meningitis
Bacteraemia
Pneumonia

X 10
X 100

Prevalence

Disease severity

Invasive

X 1000

Otitis media

Adapted from: American Academy of Pediatrics. Pediatrics. 2000;106:367-376

82

Disease burden due to S. pneumoniae


Disease

% pneumococcus*

Post neonatal pyogenic meningitis

30%

Community acquired pneumonia

15-44%

Bacteremia under 2 yrs

70- 90%

Acute otitis media

30-40%

*Western data after the introduction of Hib vaccine and


before the pneumococcal vaccine

83

Pneumonia Deaths in children < 5 years

3 million deaths due to ARI in developing countries in 0-5


0.7-1 million due to pneumococcus

84

How will you manage this case ?


Intercostal drainage and antibiotics
Which antibiotic ?
Penicillin G OR Ampicillin OR Amoxycillin

Which route ?
Parenteral (IV) for severe infections
Sequential parenteral-oral after patient improves

What dose ?
Pen G 2,00,000 U/kg/day Q 6 hrly
Ampicillin 100-200 mg/kg/day Q 6 hrly
85

Why Penicillin?
Penicillin is a narrow spectrum and cheap drug
In India pneumococci show fair susceptibility to
penicillin
Rates of penicillin drug resistance
High (40-80%) in Taiwan, Korea, Thailand, Sri Lanka,
Vietnam
Less than 10% in India, Pakistan, Australia
India: IBIS (93-97) 1.3%, ANSORP (96-97) 3.8-12.8%

But increasing prevalence expected


86

The Spread of Penicillin Resistant S. pneumoniae in Asia

80%
10%

39%

4%
58%

41%

61%

9%
23%

Song et al. Clin Inf Dis 1999;28:1206-1211

65%

21%

87

Penicillin resistance in S. pneumoniae


Intermediate resistance
MIC 0.1 1.0 g/ml
Will respond to higher dose of penicillin (2 X usual dose)
Will respond to ceftriaxone/ cefotaxime

High level resistance


MIC = 2.0 g/ml or greater
Will not respond to any lactam antibiotic
Options: Vancomycin / Linezolid, Newer (respiratory)
quinolones, carbapenems
88

When to suspect drug resistance?

Local Epidemiologic data


H/o Day care
H/o previous hospitalization
H/o previous treatment with a penicillin
especially in past 1 mth
Failure to show clinical response in 48 hrs
Culture and sensitivity testing
89

Progress in our patient.

Persistent fever & toxicity


Continuous drainage, no collection
No other clinical focus for fever
Culture report received
S. pneumoniae
Resistant to penicillin
MIC levels - 2 g/ml (high resistance)
90

Should we switch to coamoxyclav ?


Reason for drug resistance in pneumococci
is change in Penicillin Binding Protein (PBP)
Resistance is not due beta-lactamases
Therefore using co-amoxyclav will not help

91

In our case.
High resistance to penicillin
Changed to ceftriaxone ( 100 mg/kg/day q 12
hourly)
Patient afebrile after 4 days, drain removed
Discharged on high dose oral amoxicillin (80
mg/kg/day)

92

Could we have prevented this illness ?


Yes
Vaccines are available

93

Question

Should we vaccinate against


pneumococcus ?
Answer

What is the disease burden?

Large

How dangerous or severe is the


disease?

Morbidity, mortality and


sequelae

How easy it is to diagnose the


disease?

Possible but not easily


available

Is effective treatment available?

Yes but emerging


resistance

Is an effective vaccine available?

Yes (55-60% protection)

Is the vaccine safe?

Yes

What is the cost-benefit ratio?

94

Target groups for vaccination


All children < 2 yrs especially preterm, day care and
bottle fed
Children with comorbidities

Cong. immunodeficiency/ HIV


Organ transplant recipients
Sickle cell disease, asplenia
Chronic cardio-pulmonary disease
CRF, nephrotic syndrome
Diabetes mellitus
Cerebrospinal fistula, existing cochlear or other implants
95

Which vaccine to use ?


Considerations
Serotype distribution of Pneumococci
Type of Vaccine
Simple polysaccharide vaccine
Conjugated polysaccharide vaccine

96

Pneumococcal Sero-epidemiology
90 serotypes; but 13 serotypes cause 75% of
IPD globally
Vary between countries, age, site of infection
Developed countries - 14, 6, 19, 18, 9, 23, 7, 4,
1, 15
India (IBIS) - 6, 1, 19, 14, 4, 5, 45, 12, 7, 23
Immunity is sero type specific
Therefore vaccines have to be polyvalent
incorporating several different antigens
97

Which pneumococcal serogroups are responsible for invasive


disease? May depend on how hard you look.
Blood Culture Threshold
Severe pneumonias
meningitis

Increasing Clinical
Severity

Hosp. pneumonias
Ambulatory
bacteremia;
Borderline
pneumonias

1 5 14 12
1 56
14 19
23 9 7

4 6 9 14
19 19 6

very high

Latin America

high

23 14
18
14
19 19 6
18
23
14 19 19 6
14
18
4 6 9 14

Non-bacteremic
pneumonias?
Mild fever but no
medical care sought

Poorer developing
countries?
W. Europe

low

Australia

U.S./Canada

(Pneumo serogroups)

???

98
The Invasive Pneumococcal Disease Iceberg, from W.Hausdorff

Pneumococcal vaccines
Parameter

Conjugate

Simple

Basis

Poly + protein T
cell dependent

T cell independent

Immunity

Strong and long


lasting

Variable and short


lasting

Age pre requisites

Can be given
below 2

Only after age 2

Serotypes covered

23

Reduction in nasopharyngeal carriage

Yes

No effect

Herd immunity and


reduction of DRSP

Reported

?
99

Conjugate Vaccine
7 valent (4, 6B, 9V, 14, 18C, 19F, 23F)
Covers 85% serotypes in developed countries, including
most DRSP
US data shows

94% reduction in IPD in those vaccinated (min impact on AOM)


20% reduction in radiologically diagnosed pneumonia
Reduction of IPD across all ages due to herd effect
Very few adverse effects

Incorporated in US routine immunization schedule


Current vaccine covers 55-60% serotypes in India
Vaccine with more serotypes under development
100

Vaccination Schedule
Conjugate vaccine
Routine vaccination

Three doses (0.5 ml IM) - 6 weeks, 10 weeks & 14 weeks


Booster dose (0.5 ml IM) at 15-18 months

Catch up vaccination
7-11 months of age 2 primary doses at least 4 weeks apart and 1
booster
12-23 months of age 1 primary dose and 1 booster
24 months and older (only high risk) 1 dose

Simple polysaccharide vaccine


Indicated only in high risk children more than 2 years of age
Single dose 0.5 ml IM
Single booster 3-5 years later

101

IAP recommendations for pneumococcal


vaccines
High risk children
Definitely give both conjugate vaccine followed by
simple polysaccharide vaccine as per schedule

Child < 2 yrs with no high risk factors


Offer conjugate vaccine after one- one discussion
with the parents / care-givers of the child

Child > 2 yrs with no high risk factors


Vaccination not required
102

Pneumococcal Disease is
Common
Pneumococcal disease is the No. 1 cause of vaccinepreventable mortality

Serious
Mortality rates of upto 40%
Serious morbidity such as seizures, mental handicap,
hearing loss, motor deficits, restrictive lung disease due to
pleural thickening, etc.

Preventable
Existing vaccines can save lives starting now
103

Module 4
The child with fever

Case 1

20 day old neonate


Birth weight 2.5 kg, term
Exclusively breast fed
Fever of 1 day duration

105

What will you ask for ?

Whether and how was fever documented


Is the child feeding well
Excessive crying
Any localizing signs
Perinatal history and problems

106

What will you look for ?

Vitals, Lethargy, NNR


Current weight and weight gain
Rash, umbilical site, icterus, pallor
Fontanel
Otoscopy
Joints and bones
Abdominal distension, hepatosplenomegaly
Detailed systemic examination
107

History and findings

No localizing signs
Feeding normally
Axillary temperature 37.5 C (99.5F)
Activity, NNR normal
No pallor, rash or jaundice
Otoscopy, fontanel normal
Abdomen soft, no organomegaly
108

Well looking febrile neonate


What will you do ?

Hospitalization
Sepsis evaluation
Antibiotics ?

109

Why hospitalize?
High risk of serious bacterial infection (1015% SBI, 5% bacteremia) in infants less than
3 mths with fever
Risk greatest in those less than 1 mth
May look well and still have SBI
Serious outcome if missed

110

What tests for sepsis ?

CBC with band cells &


platelet count
Urine routine
CRP if available
MP (if suspicion)
Stool routine and culture
(if diarrhea)
CXR if indicated
Blood and Urine cultures
CSF examination

Test*

Sens

Spec

TLC< 5000

30

90

TLC > 20,000


(after 3 days)

75

50

ANC < 1800

90

75

I:T >0.2

95

50

CRP > 1mg/dl


(10 mg/l)

80

85

TLC <5000,
I:T> 0.2,
CRP> 1
Any 2/3
positive

100

83

111

CSF should definitely be done if


administration of antibiotics is planned

Empirical IV antibiotics in well looking febrile


neonate

Advocated by most Western Protocols


Immediately after sending screen, cultures and CSF
IV cefotaxime/ ceftriaxone with aminoglycoside
Pros
The screen is not 100% sensitive
Over cautious, will not miss any sepsis

Cons
Over use of antibiotics

113

Well looking febrile neonate


Management options
Basic, Cultures
AND
1. LP
2. Empirical IV Antibiotics
Basic
AND
Cultures
Basic
1. Hospitalization
2. CBC, CRP, Urine R/M
3. If indicated MP, Stool, CXR

114

Results in index case

WBC count 12,000/ cu mm


I:T ratio 0.1
Platelet count 1,80,000 / cu. mm.
Normal urine analysis
MP negative
CRP 0.6 mg/dl
Cultures and LP not done
115

What will you do next?

Observation in hospital without antibiotic


Repeat CBC, CRP after 6-12 hours

116

Further progress
Repeat screen
TLC of 4000
I:T ratio 0.3
CRP 2.4 mg/dl

Child looking well, but still febrile

117

What will you do ?

Blood culture, Urine culture


LP
IV cefotaxime and amikacin
Vitamin K

118

Case 1- Further progress


CSF routine normal
Child afebrile 48 hours later
All cultures negative

119

What will you do further?


Continue IV antibiotics
Duration of therapy
Culture negative sepsis 7 days
Culture positive 14 days
Meningitis 21 days

120

Management algorithm
Fever > 38C in less than 90 days, no focus
Well looking
< 1 month
Hospitalize
Screens
Normal
WBC 5000-15,000
No bandemia, CRP -ve
Urine normal

Sick looking
> 1 month
OPD
Screen

Hospitalize
CBC, CRP, Urine,
LP, Cultures
IV antibiotics

Abnormal
Repeat screen if needed
121
Observe till afebrile

Fever without focus 3-36 mths


Sick looking
Serious illness

Hospitalize
Investigations
Treatment
TLC > 15,000
Blood C/S,
Abx

Well looking

Fever > 39C/102.20F


CBC, MP, Urine

Fever < 39C

Observe, antipyretics
Explain danger signs
FU at 48 hrs

TLC < 15,000

Fever persists
No focus

CBC, MP, Urine if not done


122
Blood C/s (enteric)

Case 2

6 year old female


Monsoon
Fever 4 days
High grade, continuous, no chills
Poor appetite

123

What are your differentials ?

Enteric fever (typhoid, paratyphoid)


Malaria
Viral fever including dengue
UTI

124

What will you ask for ?

Pattern of fever onset


Concurrent similar cases in locality
Sick contact
Is the child well when fever is down
Arthralgia and Myalgia
H/o travel and eating outside food
Typhoid vaccine
Localizing symptoms
125

What will you look for ?

PR, BP, CFT


Hess test
Skin rash
ENT
Effusions, Ascites
Hepatosplenomegaly
Systemic exam including meningeal signs

126

Case 2- History & PE

Cases of dengue in the locality


Received typhoid vaccine 3.5 yrs back
Other history negative
Normal vitals, BP
Hess test negative
No rash
Systemic exam normal
127

What investigations ?
CBC with platelet count
Peripheral smear for MP
Urine R/M

128

What about other tests ?

SGPT
CXR PA view not required
Rapid Malaria antigen tests
Blood cultures
WIDAL

129

Rapid Tests Vs Thick Smears


Thick smears are gold standard
Rapid tests useful when microscopy not
available and/or not reliable
In suspected malaria that is smear negative,
rapid tests may be requested but repeat thick
smears also
Parasite LDH (Optimal) preferred over HRP -2
Ag (Parasight F)
130

Why send blood cultures ?


Should send if available
Salmonella is cultured easily
Diagnosis is unequivocal
Gives antimicrobial sensitivity
Serologic tests (WIDAL) for enteric unreliable
Cost effective in long run

Send now as sensitivity is higher (90% in first


week) and before starting Abx
131

What about WIDAL test ?


Poor sensitivity if sent early, and due to
antibiotic use
Poor specificity due to endemicity,
anamnestic reactions
Hence intelligent use needed
Send only after the first week
Consider test positive only if more than 1:
160 of both O and H/A/B
132

Investigation results

Hb 11.6
TLC 3400
P56L42E0M2
Platelet count 146000
One MP negative
Urine routine normal
Blood Culture awaited
133

What are your possibilities now ?


Dengue
Enteric fever
Malaria ?

134

Interpretation of CBC
Paramete Enteric
r

Malaria

Dengue

Other
viral

Hb/Hct

Low

N/High

TLC

N/ Low

N/Low

Low

N/ Low

DLC

Polys
eosinop
enia

Monocyto Lymphos Lymphos


sis

Platelets

N/ Low

Low

Low

N/Low
135

What will you do further ?


Daily FU (Outpatient with danger signs
explained to parents OR inpatient)
High fluid intake, paracetamol, no NSAIDS
Dengue serology ? Not useful for case
management
Serial CBCs and Repeat MP/ malaria
antigen tests
136

Why Serial CBCS ? For DHF


102F
100F
98F
96F
45
40
35
30

Fever
Hematocrit

200,000
150,000
100,000
50,000

Platelet count

5,000
4,000
3,000

WBC count

120 mm
110 mm
100 mm
90 mm
80 mm

BP
0

10

12

137

What about empiric antibiotic therapy ?


Enteric is a possibility in this case (clinical + lab)
One may start empiric antibiotics
Stop
If an alternative diagnosis is confirmed
Further clinical course unlike enteric

Continue for 14 days


If blood culture is positive for Salmonella/ WIDAL is
positive
Clinical course like enteric

138

Which empirical Abx for enteric ?


Choice of Abx depends on local resistance patterns
For outpatient therapy
Areas with high incidence of resistance to nalidixic acid (NA) & fair
sensitivity to 1st line (Amp, Chlo, TMP SMX)
Cefixime/ Azithromycin/ TMP-SMX/ Chloro

High resistance to NA as well as first line drugs


Cefixime/ Azithromycin

Low resistance to NA
Ciprofloxacin/ Ofloxacin (Not approved by DCGI)

For inpatient therapy


Ceftriaxone
139

Case Progress

Day 7 of illness
No fever
Vomiting, abdominal pain, epistaxis
Tachycardia 110/mt, BP 106/90
Tender hepatomegaly
Hb 14 gm%, TLC 3000, platelet count 1,00,000
Blood cultures sterile
140

Dengue hemorrhagic fever!

Admit
Fluid resuscitation
Careful monitoring
Stop antibiotics

141

Hospital Management of DHF


Normal circulatory status
0.9% DNS, 5 ml/kg/hr

Oxygen
Large bore IV lines
RL 20 ml/kg
Repeat upto three times
0.9% DNS 15 ml/kg/hr

Monitor clinically
Hct, platelet count
Improved
Taper fluids
over 24-48 hrs

Abnormal circulatory status

Worsened
Fluid rate
10-15 ml/kg/hr
Worsening

No improvement
CVP, inotropes,
careful fluid management
142

Module 5
Rational antimicrobial
therapy

Case 1

3 Year old
Fever, cold, cough
Difficulty in swallowing since 2 days
History of similar illness in younger sib
Febrile, Vitals WNL
Congested, enlarged tonsils
Few cervical nodes +, non-tender
Oral cefixime started
144

Are antibiotics justified?


This is probably a viral URTI
Age
Presence of coryza
Similar illness in family
No pus points on the tonsils

Antibiotics not indicated


Cefixime is not the antibiotic for respiratory
infections as it does not cover Pneumococcus
145

Case progress..
Returned one day later with continuous high
fever
Throat swab culture sent

146

Throat swab C/s in this case ?


Throat swab is indicated only with presumptive
diagnosis of bacterial sore throat
In viral sore throat throat swab may show group A beta
hemolytic streptococci (GABHS) that are probably
commensals leading to over treatment with Abx
If sending throat swab send before starting Abx

147

Case progress.
2 days later child is better
Throat swab cul.
Beta hemolytic strept.
resistant to penicillin
Antibiotics changed to Coamoxiclav

148

Sensitivity of GABHS in this case ?


Group A beta hemolytic streptococci are
universally sensitive to penicillin
The lab should recheck the sensitivity report
Prescribing Abx at the outset was the first error
Changing to coamoxiclav was the 2nd error

149

Case 2

8 mon. female, wt 8 kg
Loose stools for 2 days, no blood
Fever and vomiting present
Severe dehydration
Admitted, IV fluid, IV amikacin
Stool exam. WBC 5-6 / HPF, Few RBC / HPF
On discharge, Norflox + Metro combination

150

Are antimicrobials justified ?


Most likely cause rota virus or ETEC
Shigella unlikely as no blood
This type of diarrhoea is self limiting, no
benefit by antibiotics
Mainstay of treatment is ORS, continuation
of feeding and zinc for 14 days

151

But the stool examn report ?


Presence of few WBC & RBC in stool does
not indicate invasive infection.
It can be with any infection including viral
diarrhea
Visible blood is a more reliable indicator of
shigellosis
Stool examination is not routinely indicated

152

When should Abx be given in diarrhea ?


Bloody diarrhea
Cholera
Diarrhea associated with systemic infection

153

Comment on choice of amikacin as Abx


Abx not indicated in this case
Even if indicated amikacin is not appropriate
Suggested Abx for bloody diarrhea
First line Ciproflox/ Norflox but not approved by DCGI
IInd line- azithromycin, cefixime, ceftriaxone

Abx not indicated for bloody diarrhea

Furazolidone
I and II gen cephalosporins
aminoglycosides, colistin, amoxycillin, chloramphenicol
sulfonamides, nitrofurantoin
154

Need for metronidazole ?


Amoebiasis uncommon in young children
(2% of acute childhood diarrhea (< 5 yrs)
Indicated only if
If two diff. antibiotics usually effective for
shigella given sequentially fail
Microscopic exam. of fresh stool done in a
reliable lab shows trophozoites of E. Histolytica
containing RBC
155

Case 3

Day 0, Neonate
36 weeks, 2.0 kg
C section, no asphyxia
No PROM/no maternal fever/ foul smelling liquor
Kept in nursery for observation
Started on IV cefotaxime and amikacin

156

Are antibiotics justified ?


Prophylactic perinatal Abx are not indicated unless
PROM more than 18 hours
Maternal fever, foul smelling liqour
Positive GBS swab (Western guidelines)

Prophylactic Abx do not reduce bacterial


superinfection
They increase risk of bacterial resistance, mask
signs of evolving infection
Infection control strategies are needed not Abx
157

Prophylactic antibiotics
The benefit of prophylactic antibiotics is limited
Extensive, broad spectrum antimicrobial use may
enhance emergence of resistance
Definite Prerequisites
Specific organism against which prophylaxis is planned
Increased susceptibility of the host against that particular
infection

158

Prophylaxis- Rational Examples

Penicillin prophylaxis for Rheumatic fever


Neonate exposed to open TB in the mother
Prophylaxis for infective endocarditis
Perioperative narrow spectrum Abx for surgical
prophylaxis
Penicillin prophylaxis in asplenia
Chemoprophylaxis for recurrent UTI
Chemoprophylaxis for Malaria in travelers
Chemoprophylaxis for opportunistic infections in HIV

159

Donts in Abx therapy


Antibiotics without any attempt to document infection,
sending cultures
Treating viral infections with Abx to prevent bacterial super
infection
Indiscriminate use of broad-spectrum oral abx for routine
infections
Immediate starting of higher abx such as meropenem,
vancomycin in community acquired infections
Giving 2-3 of the same class of antibiotics e.g Augmentin and
Ceftriaxone/ampicillin
Changing of antibiotics every 24-48 hrs
Switch over to oral/ IM Abx in serious infections such as
neonatal sepsis, meningitis

160

Thank You!