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1.
BMC Infect Dis ; 11: 323, 2011 Nov 21.
Article in English | MEDLINE | ID: mdl-22103652

ABSTRACT

BACKGROUND: Prior to the availability of generic third-generation cephalosporins, penicillins were widely used for treatment of pneumococcal meningitis in developing countries despite concerns about rising levels of penicillin resistance among pneumococcal isolates. We examined the impact of penicillin resistance on outcomes of pneumococcal meningitis over a ten year period in an infectious diseases hospital in Brazil. METHODS: Clinical presentation, antimicrobial therapy and outcomes were reviewed for 548 patients with culture-confirmed pneumococcal meningitis from December, 1995, to November, 2005. Pneumococcal isolates from meningitis patients were defined as penicillin-resistant if Minimum Inhibitory Concentrations for penicillin were greater than 0.06 µg/ml. Proportional hazards regression was used to identify risk factors for fatal outcomes. RESULTS: During the ten-year period, ceftriaxone replaced ampicillin as first-line therapy for suspected bacterial meningitis. In hospital case-fatality for pneumococcal meningitis was 37%. Of 548 pneumococcal isolates from meningitis cases, 92 (17%) were resistant to penicillin. After controlling for age and severity of disease at admission, penicillin resistance was associated with higher case-fatality (Hazard Ratio [HR], 1.62; 95% Confidence Interval [CI], 1.08-2.43). Penicillin-resistance remained associated with higher case-fatality when initial therapy included ceftriaxone (HR, 1.68; 95% CI 1.02-2.76). CONCLUSIONS: Findings support the use of third generation cephalosporin antibiotics for treatment of suspected pneumococcal meningitis even at low prevalence of pneumococcal resistance to penicillins.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Meningitis, Pneumococcal/drug therapy , Meningitis, Pneumococcal/microbiology , Penicillin Resistance , Streptococcus pneumoniae/drug effects , beta-Lactams/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , Child , Child, Preschool , Female , Hospitals , Humans , Infant , Infant, Newborn , Male , Meningitis, Pneumococcal/mortality , Microbial Sensitivity Tests , Middle Aged , Treatment Outcome , Young Adult
2.
J Infect Dis ; 202(10): 1577-84, 2010 Nov 15.
Article in English | MEDLINE | ID: mdl-20932170

ABSTRACT

Since the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, meningitis caused by serotypes other than Hib has gained in importance. We conducted active hospital-based surveillance for meningitis over an 11-year period in Salvador, Brazil. H. influenzae isolates were serotyped and analyzed by polymerase chain reaction, pulsed-field gel electrophoresis, and DNA sequencing to identify strains with a specific deletion (IS1016) in the bexA gene (IS1016-bexA). We identified 43 meningitis cases caused by non-type b H. influenzae: 28 (65%) were caused by type a (Hia), 9 (21%) were caused by noncapsulated strains, and 3 (7%) each were caused by types e and f. Hia isolates clustered in 2 clonal groups; clonal group A strains (n = 9) had the IS1016-bexA deletion. Among children <5 years of age, meningitis caused by Hia from clonal group A had higher case-fatality than meningitis caused by clonal group B. Despite small numbers, these results indicate that the presence of the IS1016-bexA deletion is associated with enhanced virulence in non-type b H. influenzae.


Subject(s)
ATP-Binding Cassette Transporters/genetics , Bacterial Proteins/genetics , Haemophilus/genetics , Meningitis, Haemophilus/microbiology , Base Sequence , Brazil/epidemiology , Child, Preschool , Female , Gene Deletion , Haemophilus/classification , Haemophilus/pathogenicity , Hospitals, Municipal , Humans , Incidence , Infant , Male , Meningitis, Haemophilus/epidemiology , Molecular Sequence Data , Phylogeny , Sentinel Surveillance , Sequence Alignment , Virulence/genetics
3.
Vaccine ; 25(22): 4420-8, 2007 May 30.
Article in English | MEDLINE | ID: mdl-17449150

ABSTRACT

The long-term impact of Haemophilus influenzae type b (Hib) conjugate vaccine, introduced throughout Latin America in the late 1990s, has not been evaluated. Active surveillance for H. influenzae meningitis was performed from August 9, 1996 to August 8, 2004 in Metropolitan Salvador, Brazil. Five years after the introduction of Hib conjugate vaccine, Hib meningitis incidence decreased from 2.39 to 0.06 cases per 100,000 population (98%) overall, and from 60.9 to 3.1 cases per 100,000 population (95%) in children <1 year of age. A transient serotype replacement phenomenon was observed associated with a small increase of meningitis due to two H. influenzae type a clonal groups. These findings indicate that Hib immunization campaign has led to the virtual elimination of Hib disease in this region.


Subject(s)
Haemophilus Vaccines , Haemophilus influenzae type b/immunology , Immunization Programs , Meningitis, Haemophilus/epidemiology , Population Surveillance , Tetanus Toxoid , Vaccines, Conjugate , Brazil/epidemiology , Child , Child, Preschool , Haemophilus Vaccines/administration & dosage , Haemophilus Vaccines/immunology , Haemophilus influenzae type b/classification , Haemophilus influenzae type b/isolation & purification , Humans , Incidence , Infant , Infant, Newborn , Meningitis, Haemophilus/microbiology , Meningitis, Haemophilus/mortality , Meningitis, Haemophilus/prevention & control , Program Evaluation , Serotyping , Tetanus Toxoid/administration & dosage , Tetanus Toxoid/immunology , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/immunology
4.
J Infect Dis ; 187(1): 109-16, 2003 Jan 01.
Article in English | MEDLINE | ID: mdl-12508153

ABSTRACT

Surveillance for Haemophilus influenzae meningitis cases was performed in Salvador, Brazil, before and after introduction of H. influenzae type b (Hib) immunization. The incidence of Hib meningitis decreased 69% during the 1-year period after initiation of Hib immunization (from 2.62 to 0.81 cases/100,000 person-years; P<.001). In contrast, the incidence for H. influenzae type a meningitis increased 8-fold (from 0.02 to 0.16 cases/100,000 person-years; P=.008). Pulsed-field gel electrophoretic analysis demonstrated that H. influenzae type a isolates belonged to 2 clonally related groups, both of which were found before Hib immunization commenced. Therefore, Hib immunization contributed to an increased risk for H. influenzae type a meningitis through selection of circulating H. influenzae type a clones. The risk attributable to serotype replacement is small in comparison to the large reduction in Hib meningitis due to immunization. However, these findings highlight the need to maintain surveillance as the use of conjugate vaccines expands worldwide.


Subject(s)
Haemophilus Vaccines/immunology , Haemophilus influenzae type b/classification , Haemophilus influenzae/classification , Meningitis, Haemophilus/prevention & control , Polysaccharides, Bacterial/immunology , Bacterial Capsules , Brazil , Child , Child, Preschool , Female , Haemophilus influenzae/pathogenicity , Humans , Immunization , Infant , Male , Meningitis, Haemophilus/microbiology , Serotyping , Virulence
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