Long-term sequelae associated with pneumococcal disease

Transcription

1 Long-term sequelae associated with pneumococcal disease Dr. Jesús s M. Feris Hospital Infantil Dr. Robert Reid Cabral República Dominicana Simposio Subregional del Caribe Sobre Neumococo Hotel V Centenario Octubre 1 y 2, 2008 Santo Domingo, República Dominicana

2 Porcentaje Agentes Causales de Meningitis Bacteriana. Red SIREVA de Rep.Dom n= Hib Spn Nm

3 600 Bacterial meningitis by year Hospital Infantil Dr. Robert Reid Cabral, All cases Number of cases Hib Spn Partial HibCV Introduction HibCV 10 0 Nm *

4 Number of cases of acute bacterial meningitis according to study period ( and ) and bacterial pathogen, among 218 patients with acute bacterial meningitis (Hospital Infantil de México Federico Gómez, ( ) Bacterial pathogen Total No. Cases (%) Period before the Introdution of Hib vaccine, Period after the Introdution of Hib vaccine, No. Cases (%) No. Cases (%) All 218 (100) 159 (100) 59 (100) Hib 109 ( 50 ) 101 ( 64 ) 8 ( 14 )* Spn 67 ( 31 ) 35 ( 22 ) 32 ( 54 ) Nm 4 ( 2 ) 1 ( 0.5 ) 3 ( 5 ) Other 14 ( 6 ) 9 ( 5.5 ) 5 ( 8 ) No pathogen 24 ( 11 ) 13 ( 8 ) 11 ( 19 ) * 6/8 (75%) children > 4 years of age and did not received previous Hib vaccination. Ref: Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year experiencie ( ). Franco-Paredes C, Lammoglia L, Hernandez I, Santos JI. Int J infect Dis (2007), dol: /j.ijid

5 Streptococcus pneumoniae Meningitis in Dominican Children: Age distribution Age (years) < 1 > 1-5 > 5 Total n % Ref: Feris J. Fernandez J. Sanchez J. et al: 44 th. ICAAC, Oct 30-Nov 2, Washington, D.C. USA, 2004, Paper # 3212

6 Clinical presentation and prognostic factors of Streptococcus pneumoniae meningitis according to the focus of infections (Denmark) n=187 Most common focus Ear Lung Sinus Other Undetermined % Ref: Ostergaard C, Koradsen HB, Sauelsson S: BMC Infectious Diseases 2005, 5:93

7 Middle ear cultures results through tympanocentesis Departamento Enfermedades Infecciosas Hosp. Inf. Dr. Robert Reid Cabral Long-term sequelae associated with pneumococcal disease n=221 Negative 19% Hi 25% Others 8% Staph. spp8% S. pyogenes1% B. catarrhalis1% Spn 38% Ref: Infectious Diseases Department, Hospital Infantil Dr. Robert Reid Cabral, 2005.

8 Factors Associated with Hearing Loss in Dominican Children with Bacterial Meningitis n=225 Audiolical Outcome According to Etiology of Bacterial Meningitis Etiology* H. influenzae b** Normal Hearing n= % 77.3 Hearing Loss n= % 70.0 H. influenzae a S. pneumoniae N. meningitidis B and C S. agalactiae Gram negative bacilli *No bacteria were isolated in 77 CSF. ** OR=3, CI 95%:1.8,5.2,P<0.05 Ref.: Feris JM, Fernandez J, Terrero C, et al.: Abstract 147, 3rd World Congress of Pediatric Infectious Diseases, Santiago de Chile, Chile, November 19-23, 2002

9 Long-Term neurological sequelae in the Out-patient clinic, Infectious Diseases Department, (Spn meningitis) Hospital Infantil Dr. Robert Reid Cabral, Age <5 yrs 61 (88%) 5 yrs 7 (12%) Frequency n % No Sequelae Sequelae 5 yrs Hearing Loss Convulsions Motor Deficit Ref: Out-patient Clinic DEI

10 Pneumococcal meningitis in children: prognostic indicators and outcome Dept. of Pediatr, Sophia Children s Hospital/University Hospital Rotterdam, Netherlands Median age: 8 months n=83 % Mortality rate Survivors with sequelae hearing loss neurological (7-35) Ref: Kornelisse RF, Westerbeek CM, Spoor AB, et al: Clin Infect Dis Dec;21(6):1390-7

11 Clinical presentation and prognostic factors of Streptococcus pneumoniae meningitis according to the focus of infections (Denmark) n=187 Survivors with neurologic sequelae Hearing loss Focal neurological deficits Combination of both 41 % 24 % 16 % 1 % Ref: Ostergaard C, Koradsen HB, Sauelsson S: BMC Infectious Diseases 2005, 5:93

12 Clinical presentation and prognostic factors of Streptococcus pneumoniae meningitis according to the focus of infections (Denmark) n=187 Mortality by infectious focus* Otogenic Sinusitic Pneumonic Others** % *Long rank test: p = ** No primary infectious focus (21%) Ref: Ostergaard C, Koradsen HB, Sauelsson S: BMC Infectious Diseases 2005, 5:93

13 Long-term sequelae of pneumococcal meningitis in children n=90 MSpn ( ) Thessaloniki Hospital, Greece Hearing loss Sequelae Neurological handicap Mental retardation Seizure disorder Motor defects Behavioral problems Visual impairment n=47 evaluated (75%) Ref: Pikis, A, Kavaliotis J, Andrianopoulos P et al: Clinical pediatrics 1996, 35;2:72-78 n %

14 A retrospective study on 72 children admitted to a medical center in Taiwan due to invasive pneumococcal infections diagnosed between January 1990 and April 2000 Diagnosis cases Mortality % Meningitis Other invasive diseases Survived with long term sequelae Although 56.9% were penicillin resistant the outcome was not associate with susceptibility Ref: Ma JS, et al: J Microbiol Immunol Infect 2002;35(1):23-8

15 Relationship between mortality in patiens with Meningitis SpnRP vs SpnSP SP Departamento de Enfermedades Infecciosas, Hospital Infantil Dr. Robert Reid Cabral, Jun Dic 2003 Deaths SPRP** SPSP*** OR CI 95% Yes No 21 (24.4%) 56 (24.2%) 65 (75.5%) 175 (75.8%) ,1.91 Total **S. pneumoniae Resist to Penicillin *** S. pneumoniae Sensible to Penicillin Ref: Feris J, Fernández J, Sachez J, et al: et al. ICAAC 44th Washington DC, 2004, Paper # 3412

16 Clinical Outcomes of Meningitis Caused by Streptococcus pneumoniae in the Era of Antibiotic Resistance Outcome Died during hospitalization Length of hospitalization (d) Length of stay in ICU (d) Required ICU admission Required supplemental oxygen Required mechanical ventilation Discharged to long-term-care facility Discharged with neurological deficit(s) Cefotaximenonsusceptible (n = 22) 2/22 (9) 19.3 ± ± /20 (50) 9/19 (47) 5/22 (23) 3/20 (15) 4/20 (20) Cefotaximesusceptible (n = 87) 13/87 (15) 14.1 ± ± /74 (55) 52/85 (61) 28/87 (32) 16/73 (22) 9/74 (12 Ref: Clinical Infectious Diseases 2000;30:71-77

17 Ceftazidime vs. standard therapy for pediatric meningitis: therapeutic, pharmacologic and epidemiologic observations. Mortality by pathogen Microorganism H. influenzae S. pneumoniae N. meningitidis Salmonella spp. n 3 / 42 8 / 17 1 / 17 1 / 3 % Ref: Rodriguez WJ, Puig J, Khan WN, Feris J, et al. Pediatr Infect Dis Jul-Aug;5(4):

18 Sulbactam/ampicillin vs. chloramphenicol/ampicillin for the treatment of meningitis in infants and children Mortality by pathogen among 81 patients with meningitis Microorganismo H. influenzae S. pneumoniae N. meningitidis Other No growth n % Ref: Rodríguez WJ, Khan WN, Puig J, Feris, J, et al. Rev Infect Dis Suppl 5:S620 S629.Nov Dec

19 Phagocytosis Resistency

20 Pneumococcal Virulence Factors Ref: Microbiol Mol Biology Rev 2001;65:

21 Infections due to Spn Penicillin Resistant in USA DEI

22 Streptococcus pneumoniae Penicillin Sensible from CSF Hospital Infantil Dr. Robert Reid Cabral, Santo Domingo, Rep. Dominicana n=197 Sensible Intermediate Resistant

23 Streptococcus pneumoniae Cefotaxime Sensible from CSF Hospital Infantil Dr. Robert Reid Cabral, Santo Domingo, Rep. Dominicana n=186 Sensible Intermediate Resistant

24 Susceptibility of Streptococcus. pneumoniae to penicillin < 6 years old % S I R Argentina Brazil Chile Dominican R Paraguay Venezuela SIREVA II - LATIN AMERICAN GROUP

25 Geographic region with: 5% Spn PR Use Cefotaxime or Ceftriaxone 5% Spn CR Use Vancomycin + Cefotaxime or Ceftriaxone ¹-². 1. Friedland Ian R.: Antimicrobial Agents and Chemotherapy, Sept 1997, p Odio Pérez, Carla M.:Acta pediátr. Costarric v. 15 n.3 San José 2001

26 Cost-effectiveness using different antibiotics in Bacterial Meningitis Antibiotics Penicillin G Ampicillin Chloramphenicol Cefotaxime Ceftriaxone Vancomycin Meropenem Cost * US$12.00/day US$29.00/day US$27.00/day US$130.00/day US$160.00/day US$62.00/day US$325.00/day * Estimates in adults at the higher doses/day Ref.: Current Treatment options in Infectious Diseases 2000, 2:

27 Costs* of pneumococcal disease in a cohort of 340,000 Canadian children from six months to nine years of age Costs to health system Costs to families Costs to society Meningitis $649,000 $97,000 $746,000 Hospitalized bacteremia $1,070,000 $655,000 $1,725,000 Nonhospitalized bacteremia $34,000 $71,000 $105,000 Hospitalized pneumonia $5,022,000 $4,108,000 $9,130,000 Nonhospitalized pneumonia $1,261,000 $7,748,000 $9,009,000 Acute otitis media $15,148,000 $69,008,000 $84,156,000 Myringotomy with ventilation tube insertion $16,872,000 $3,958,000 $20,830,000 Total $40,224,000 $85,477,000 $125,701,000 * 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 Jul Aug; 14(4):

28 Mortalility associated to Bacterial Meningitis in the last 90 years N ENGL J MED ; DEI

29 Comparison of oral cefuroxime axetil and oral amoxycillin/clavulanate in the treatment of communityacquired pneumonia Organism Isolated* Streptococcus pneumoniae Haemophilus influenzae n=97/ % Pretreatment. Respiratory tract fluid specimen: deep expectorated sputum, endotracheal suction, bronchial washing, transtracheal aspirate. Gram stain of sputum: <10 epithelial cells/pf and >25 polymorphonuclear leucocytes/pf. Ref: Higuera F, Hidalgo H, Feris J, et al: Journal of Antimicrolbial Chemotherapy (1996) 37,

30 Empiema Pleural en el Departamento de Infectología Hospital Infantil Dr. Robert Reid Cabral Santo Domingo, X=151/year Hospitalizaciones Empiemas pleurales DEI

31 Parapneumonic effusions and empyema in hospitalized children: retrospective review of 227 cases 227 Clinical records in 19 years review: Parkland Memorial Hospital and Children s Medical Center, Dallas. Etiology No. Cases Jan 64-Jun 73 Jul 73-Dec 82 Total S. aureus 43 (34) 23 (23) 66 (29) S. pneumoniae 27 (22) 22 (22) 49 (22) Haemophilus 15 (12) 25 (25) 40 (18) Otras bacterias 8 (6) 10 (10) 18 (8) Sterile 32 (26) 22 (22) 54 (24) All cases 125 (100) 102 (100) 227 (100) Ref: Freij,, BJ, MD, Lkusmiesz,H RN, Nelson, JC, MD, and Mccracken,, GH, jr., MD: Pediatr Inf Dis 1984;3:

32 Empyema associated with community-acquired pneumonia: A Pediatric Investigator's Collaborative Study on Infections in Canada (PICNIC) study n=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: /

33 More Frequent Distribution Bacterial Isolated by year from Pleural Fluid Departamento de Infectología del Hospital Infantil Dr. Robert Reid Cabral, República Dominicana, S. pneumoniae S. aureus H. influenzae DEI

34 Cases of Pleural Empyema by age admitted to Infectious Diseases Department Hospital Infantil Dr. Robert Reid Cabral, Age n % % accumulate 0-6 months months months years > 5 years Unknown Total 1, Ref: Infectious Diseases Department, Hospital Infantil Robert Reid Cabral

35 S.pneumoniae Serotypes-serogroups Identify in Patients with Pneumonia, Dominican Republic, n= PCV7 coverage: 78% A/6B /19A 23/23F 7/7F 9/9V 5 18/18A Otros 4 * PCV7: 4, 6B, 9V, 14, 18C, 19F y 23F

36 Conclusions Streptococcus pneumoniae is the leading cause of bacterial meningitis and pneumonia. Spn meningitis causes high rate long term sequelae, principally neurological and hearing loss. 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.