Long-term sequelae associated with pneumococcal disease
Dr. JesDr. Jesúús M. Feriss M. FerisHospital Infantil Dr. Robert Reid CabralHospital Infantil Dr. Robert Reid Cabral
RepRepúública Dominicanablica Dominicana
Simposio Subregional del Caribe Simposio Subregional del Caribe Sobre NeumococoSobre Neumococo
Hotel V CentenarioHotel V CentenarioOctubre 1 y 2, 2008Octubre 1 y 2, 2008
Santo Domingo, RepSanto Domingo, Repúública Dominicanablica Dominicana
Agentes Causales de Meningitis Bacteriana.Red SIREVA de Rep.Dom
2000-2007n=405
0102030405060708090
100
2000 2001 2002 2003 2004 2005 2006 2007
Porc
enta
je
Hib Spn Nm
Bacterial meningitis by year Hospital Infantil Dr. Robert Reid Cabral, 1994-2007
0102030405060708090
100
1994
1995
1996
1997
1998
1999
2000
*2001
2002
2003
2004
2005
2006
2007
Num
ber o
f cas
es
Introduction HibCVPartial HibCV
200
300
400
500
600
All cases
HibHib
SpnSpn
NmNm
Number of cases of acute bacterial meningitis according to study period(1993-1998 and 1999-2003) and bacterial pathogen, among 218 patients
with acute bacterial meningitis (Hospital Infantil de México Federico Gómez, (1993-2003)
59 (100)8 ( 14 )*32 ( 54 )
3 ( 5 )5 ( 8 )
11 ( 19 )
159 (100)101 ( 64 )35 ( 22 )1 ( 0.5 )9 ( 5.5 )13 ( 8 )
218 (100)109 ( 50 )67 ( 31 )
4 ( 2 )14 ( 6 )
24 ( 11 )
AllHibSpnNmOtherNo pathogen
Period after theIntrodution of Hibvaccine,1999-2003 No. Cases (%)
Period before theIntrodution of Hibvaccine,1993-1998 No. Cases (%)
Total No.Cases (%)
Bacterial pathogen
Ref: Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year experiencie(1993-2003). Franco-Paredes C, Lammoglia L, Hernandez I, Santos JI. Int J infect Dis (2007), dol:10.1016/j.ijid.2007.09.012
* 6/8 (75%) children > 4 years of age and did not received previous Hib vaccination.
Streptococcus pneumoniae Meningitis in Dominican Children: Age distribution
100317Total
12.138> 5
27.788> 1 - 5
60.2191< 1
%nAge (years)
Ref: Feris J. Fernandez J. Sanchez J. et al: 44th. ICAAC, Oct 30-Nov 2, Washington, D.C. USA, 2004, Paper # 3212
Clinical presentation and prognostic factors of Streptococcus pneumoniae
meningitis according to the focus of infections (Denmark)
n=187
Ref: Ostergaard C, Koradsen HB, Sauelsson S: BMC Infectious Diseases 2005, 5:93
42Undetermined2Other8Sinus
18Lung30Ear%Most common focus
Middle ear cultures results through Middle ear cultures results through tympanocentesistympanocentesisDepartamentoDepartamento EnfermedadesEnfermedades InfecciosasInfecciosas
Hosp. Inf. Dr. Robert Reid Cabral Hosp. Inf. Dr. Robert Reid Cabral 19881988--20042004
Negative 19%
Others 8%
S. pyogenes1%
Staph. spp8%
B. catarrhalis1%
Hi 25%
Spn 38%
n=221
Ref: Infectious Diseases Department, Hospital Infantil Dr. Robert Reid Cabral, 2005.
Long-term sequelae associated with pneumococcal disease
Long-term sequelae associated with pneumococcal disease
Factors Associated with Hearing Loss in Dominican Childrenwith Bacterial Meningitis
n=225
5.062.83Gram negative bacilli0.001.92S. agalactiae7.598.59N. meningitidis B and C
16.62011.412S. pneumoniae0.811.92H. influenzae a
70.08477.377H. influenzae b**%n=120%n=105
Hearing LossNormal HearingEtiology*
Audiolical Outcome According to Etiology of Bacterial Meningitis
*No bacteria were isolated in 77 CSF.** OR=3, CI 95%:1.8,5.2,P<0.05Ref.: Feris JM, Fernandez J, Terrero C, et al.: Abstract 147, 3rd World Congress ofPediatric Infectious Diseases, Santiago de Chile, Chile, November 19-23, 2002
LongLong--Term neurological sequelae Term neurological sequelae in the Outin the Out--patient clinic, Infectious Diseases Department,patient clinic, Infectious Diseases Department,
((SpnSpn meningitis)meningitis)Hospital Hospital InfantilInfantil Dr. Robert Reid Cabral, 2000Dr. Robert Reid Cabral, 2000--20072007
35
20.422.754.591.065.0
9Motor Deficit 10Convulsions24Hearing Loss40≤5 yrs 44Sequelae
24No Sequelae
Frequency n %≥5 yrs 7 (12%)<5 yrs 61 (88%)
Age
Ref: Out-patient Clinic DEI. 2007
Pneumococcal meningitis in children: prognostic indicators and outcome
Dept. of Pediatr, Sophia Children´s Hospital/UniversityHospital Rotterdam, Netherlands 1970-1994
361925
25--
Survivors with sequelae• hearing loss• neurological
17(7-35) Mortality rate
%n=83Median age: 8 months
Ref: Kornelisse RF, Westerbeek CM, Spoor AB, et al: Clin Infect Dis. 1995 Dec;21(6):1390-7
Clinical presentation and prognostic factors of Streptococcus pneumoniae
meningitis according to the focus of infections (Denmark)
n=187
Ref: Ostergaard C, Koradsen HB, Sauelsson S: BMC Infectious Diseases 2005, 5:93
1 %• Combination of both16 %• Focal neurological deficits24 %• Hearing loss41 %Survivors with neurologic sequelae
Clinical presentation and prognostic factors of Streptococcus pneumoniae
meningitis according to the focus of infections (Denmark)
n=187
Ref: Ostergaard C, Koradsen HB, Sauelsson S: BMC Infectious Diseases 2005, 5:93
50• Others**26• Pneumonic 33• Sinusitic7• Otogenic%Mortality by infectious focus*
*Long rank test: p = 0.0005** No primary infectious focus (21%)
LongLong--termterm sequelaesequelae ofofpneumococcal meningitis in pneumococcal meningitis in childrenchildren
Ref: Pikis, A, Kavaliotis J, Andrianopoulos P et al: Clinical pediatrics 1996, 35;2:72-78
201Visual impairment2
1115171930%
01Behavioral problems05Motor defects07Seizure disorder08Hearing loss09Mental retardation14Neurological handicapnSequelae
n=90 MSpn (1967 - 1988) Thessaloniki Hospital, Greecen=47 evaluated (75%)
A retrospective study on 72 children admitted to a medical center in Taiwan due to invasive
pneumococcal infections diagnosed betweenJanuary 1990 and April 2000
Although 56.9% were penicillin resistant the outcomewas not associate with susceptibility
52.610Survived with long termsequelae
13.644Other invasive diseases
32.128Meningitis
Mortality % casesDiagnosis
Ref: Ma JS, et al: J Microbiol Immunol Infect 2002;35(1):23-8
24077Total
175 (75.8%)56 (24.2%)No
0.56,1.911.03
65 (75.5%)21 (24.4%)Yes
CI 95%ORSPSP***SPRP**Deaths
****S. pneumoniaeS. pneumoniae ResistResist toto PenicillinPenicillin*** *** S. pneumoniaeS. pneumoniae Sensible Sensible toto PenicillinPenicillin
RelationshipRelationship betweenbetween mortalitymortality in in patienspatiens withwithMeningitis Meningitis SpnSpnRPRP vsvs SpnSpnSPSP
Departamento de Enfermedades Infecciosas,Departamento de Enfermedades Infecciosas,Hospital Infantil Dr. Robert Reid Cabral, Jun 1993 Hospital Infantil Dr. Robert Reid Cabral, Jun 1993 -- Dic 2003Dic 2003
Ref: Feris J, Fernández J, Sachez J, et al: et al. ICAAC 44th Washington DC, 2004,
Paper # 3412
Clinical Outcomes of Meningitis Caused by Streptococcus pneumoniae in the Era of Antibiotic
Resistance
9/74 (124/20 (20)Discharged with neurological deficit(s)16/73 (22)3/20 (15)Discharged to long-term-care facility28/87 (32)5/22 (23)Required mechanical ventilation52/85 (61)9/19 (47)Required supplemental oxygen41/74 (55)10/20 (50)Required ICU admission
7 ± 9.39.9 ± 11.9Length of stay in ICU (d)14.1 ± 11.219.3 ± 19.9Length of hospitalization (d)13/87 (15)2/22 (9)Died during hospitalization
Cefotaxime-susceptible
(n = 87)
Cefotaxime-nonsusceptible
(n = 22)Outcome
Ref: Clinical Infectious Diseases 2000;30:71-77
CeftazidimeCeftazidime vs. standard therapy for pediatric vs. standard therapy for pediatric meningitis: therapeutic, pharmacologic and meningitis: therapeutic, pharmacologic and
epidemiologic observations. epidemiologic observations.
Ref: Rodriguez WJ, Puig J, Khan WN, Feris J, et al. Pediatr Infect Dis. 1986 Jul-Aug;5(4):408-15.
5.91 / 17N. meningitidis331 / 3Salmonella spp.
478 / 17S. pneumoniae
73 / 42H. influenzae
%nMicroorganism
Mortality by pathogen
Sulbactam/ampicillinSulbactam/ampicillin vs. vs. chloramphenicol/ampicillinchloramphenicol/ampicillinfor the treatment of meningitis in infants and for the treatment of meningitis in infants and
children children
Ref: Rodríguez WJ, Khan WN, Puig J, Feris, J, et al. Rev Infect Dis. 1986 8 Suppl 5:S620–S629.Nov–Dec
205Other616No growth
08N. meningitidis
23.515S. pneumoniae
5.437H. influenzae
%nMicroorganismo
Mortality by pathogen among 81 patients with meningitis
Phagocytosis Resistency
Pneumococcal Virulence Factors
Ref: Microbiol Mol Biology Rev 2001;65:187-207
.
DEIDEI
Infections due to Infections due to SpnSpn Penicillin Resistant in USAPenicillin Resistant in USA1979 1979 -- 19991999
Streptococcus pneumoniae Penicillin Sensible from CSF Hospital Infantil Dr. Robert Reid Cabral,
Santo Domingo, Rep. Dominicana2000-2007
4242
15
61
13
26
57
18
25
4339
17
56
33
11
39
35
23
10
14 4
17
0
10
20
30
40
50
60
70
2000 2001 2002 2003 2004 2005 2006 2007
Sensible Intermediate Resistantn=197
Streptococcus pneumoniae Cefotaxime Sensible from CSF Hospital Infantil Dr. Robert Reid Cabral,
Santo Domingo, Rep. Dominicana2000-2007
77
19
3
92
4 4
74
22
4
72
20
8
87
94
79
17
3
148
28
0 4
0102030405060708090
100
2000 2001 2002 2003 2004 2005 2006 2007
Sensible Intermediate Resistantn=186
Susceptibility of Susceptibility of Streptococcus. pneumoniaeStreptococcus. pneumoniae to penicillinto penicillin20002000--2005 2005 < 6 < 6 yearsyears oldold
5963
67
42
70
29
21
33
12
21
13 11 12
25
138
75
26
Argentina Brazil Chile Dominican R Paraguay Venezuela
SIR
%
SIREVA II - LATIN AMERICAN GROUP
1. Friedland Ian R.: Antimicrobial Agents and Chemotherapy, Sept 1997, p. 1888-1891
2. Odio Pérez, Carla M.:Acta pediátr. Costarric v. 15 n.3 San José2001
Geographic region with:Geographic region with:
≥≥ 5% 5% SpnSpn PR PR Use Use CefotaximeCefotaxime or or CeftriaxoneCeftriaxone
≥≥ 5% 5% SpnSpn CR CR Use Use VancomycinVancomycin + + CefotaximeCefotaxime or or CeftriaxoneCeftriaxone ¹-²¹-²..
Cost-effectiveness using different antibiotics in Bacterial Meningitis
Cost *Antibiotics
US$325.00/dayMeropenemUS$62.00/dayVancomycin
US$160.00/dayCeftriaxoneUS$130.00/dayCefotaximeUS$27.00/dayChloramphenicolUS$29.00/dayAmpicillin
US$12.00/dayPenicillin G
* Estimates in adults at the higher doses/day
Ref.: Current Treatment options in Infectious Diseases 2000, 2:433-440
Costs* of pneumococcal disease in a cohort of 340,000 Costs* of pneumococcal disease in a cohort of 340,000 Canadian children from six months to nine years of ageCanadian children from six months to nine years of age
$125,701,000$85,477,000$40,224,000Total
$20,830,000$3,958,000$16,872,000Myringotomy with ventilation tube insertion
$84,156,000$69,008,000$15,148,000Acute otitis media$9,009,000$7,748,000$1,261,000Nonhospitalized pneumonia$9,130,000$4,108,000$5,022,000Hospitalized pneumonia$105,000$71,000$34,000Nonhospitalized bacteremia$1,725,000$655,000$1,070,000Hospitalized bacteremia$746,000$97,000$649,000Meningitis
Costs to societyCosts to families
Costs to health system
* Excluding costs of sequelae and productivity losses associated with deaths and disabilities. Assuming 22% of all cases of pneumonia, 19% of all cases of acute otitis media, and 50 % of all cases of myringotomy with ventilation tube insertion are attributable to S pneumoniae
Ref.: Can J Infect Dis. 2003 Jul–Aug; 14(4): 215–220.
N ENGL J MED 2004 351;1826-1828
Mortalility associated to Bacterial Meningitis in the last 90 years
DEIDEI
Comparison of oral cefuroxime axetil and oral amoxycillin/clavulanate in the treatment of community-
acquired pneumonia
18-Haemophilus influenzae
38-Streptococcus pneumoniae60%n=97/162Organism Isolated*
• Pretreatment. Respiratory tract fluid specimen:• deep expectorated sputum,• endotracheal suction, • bronchial washing, • transtracheal aspirate. • Gram stain of sputum: <10 epithelial cells/pf and >25polymorphonuclear leucocytes/pf.
Ref: Higuera F, Hidalgo H, Feris J, et al: Journal of Antimicrolbial Chemotherapy (1996) 37, 555-564.
Empiema Pleural en el Departamento de InfectologíaHospital Infantil Dr. Robert Reid Cabral
Santo Domingo, 1994-2004
721
203
731
172
637
127
781
213
735
168
892
148
1070
121
901
165
886
180
1019
126
1071
112
846
180
1067
125
1220
68
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Hospitalizaciones Empiemas pleurales
DEIDEI
X=151/year
ParapneumonicParapneumonic effusions and empyema in hospitalized effusions and empyema in hospitalized children: retrospective review of 227 caseschildren: retrospective review of 227 cases
227 Clinical records in 19 years review: Parkland Memorial Hospital and Children’s Medical Center, Dallas.
Ref: Ref: FreijFreij, BJ, MD, , BJ, MD, Lkusmiesz,HLkusmiesz,H RN, Nelson, JC, MD, and RN, Nelson, JC, MD, and MccrackenMccracken, GH, jr., MD:, GH, jr., MD: Pediatr
Inf Dis 1984;3:578-591
227 (100)102 (100)125 (100)All cases54 (24)22 (22)32 (26)Sterile18 (8)10 (10)8 (6)Otras bacterias40 (18)25 (25)15 (12)Haemophilus49 (22)22 (22)27 (22)S. pneumoniae66 (29)23 (23)43 (34)S. aureus
TotalJul 73-Dec 82Jan 64-Jun 73No. CasesEtiology
Empyema associated with community-acquired pneumonia: A Pediatric Investigator's Collaborative Study on Infections in
Canada (PICNIC) studyn=251
8 pediatric hospitals in a period of 3 years
< 5 years of age 57% of the cases. The median length of hospitalization was 9 days. Oxygen supplementation was required in 77%, of children 75% had chest tube placement 33% were admitted to an intensive care unit. While similarity in use of pain medication, antipyretics and antimicrobial use was observed.wide variation in number of chest radiographs and invasive procedures (thoracentesis, placement of chest tubes) was observed between centers. The most common organism found:Streptococcus pneumoniae
Ref: Joanne M Langley , James D Kellner , Nataly Solomon et al: BMC Infectious Diseases 2008, :129doi:10.1186/1471-2334-8-129
More Frequent Distribution Bacterial Isolated by year from Pleural Fluid Departamento de Infectología del Hospital Infantil Dr. Robert Reid Cabral,
República Dominicana, 1994-2007
0
10
20
30
40
50
60
70
80
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007S. pneumoniae S. aureus H. influenzae DEIDEI
Cases of Pleural Empyema by ageadmitted to Infectious Diseases Department
Hospital Infantil Dr. Robert Reid Cabral, 1994-2003
1001001,130Total
1000.44Unknown
99.519.1216> 5 years
80.429.03282-5 years
51.520.923613-23 months
30.623.52667-12 months
7.17.1800-6 months
% accumulate%nAge
Ref: 2008. Infectious Diseases Department, Hospital Infantil Robert Reid Cabral
S.pneumoniae Serotypes-serogroups Identify in Patients with Pneumonia,
Dominican Republic, 2000-2005n=146
82
21
135 6 4 4 5 2 2 2 0
0
10
20
30
40
50
60
70
80
90
14 6A/6B 1 3 19/19A 23/23F 7/7F 9/9V 5 18/18A Otros 4
* PCV7: 4, 6B, 9V, 14, 18C, 19F y 23F* PCV7: 4, 6B, 9V, 14, 18C, 19F y 23F
PCV7 coverage: 78%
Conclusions• Streptococcus pneumoniae is the leading cause of
bacterial meningitis and pneumonia.
• Spn meningitis causes high rate long termsequelae, principally neurological and hearingloss.
• Spn meningitis mortality rate is high even penicillin susceptibility or not.
• The cost of treatment is very high for the Family, Society and Heath System.