Haemophilus influenzae type-b and non-b-type invasive diseases in urban children (<5years) of Bangladesh: implications for therapy and vaccination.
OBJECTIVE
To prospectively study the epidemiology and antibiotic resistance of Haemophilus infuenzae isolates from invasive infections in children.


METHODS
Children (<5years) with pneumonia, meningitis and septicemia from three hospitals in Dhaka, Bangladesh were enrolled (1999-2003); clinical and laboratory data, and blood for cultures were collected. Cerebrospinal fluid (CSF) of meningitis cases was analyzed (Gram stain, culture and biochemical tests). Hib antigen was detected by latex agglutination (LA) in culture-negative pyogenic CSF and PCR was done for bexA gene in culture- and LA-negative pyogenic CSF. Antibiotic susceptibility was determined by E-Tests and beta-lactamase by nitrocefin stick.


RESULTS
Seventy-three cases of H. influenzae infections (46 of 293 meningitis cases, 25 of 1493 pneumonia cases, 2 of 48 septicemia cases) were detected; 63%, 34% and 3% of them had meningitis, pneumonia and septicemia respectively. H. influenzae type b (Hib) caused infections in 80.8% of cases (60.3% meningitis, 20.5% pneumonia). Most (86%) infections clustered in 4-12month infants. The case-fatality in pneumonia was 8% compared to 19% in meningitis. H. influenzae isolates from pneumonia and meningitis children were equally resistant to antibiotics (46% vs 43%). Of 10 drugs tested, isolates were resistant to ampicillin (31%), chloramphenicol (42%), trimethoprim-sulfamethoxazole (44%) and azithromycin (1.4%). Multidrug-resistant (MDR) strains were equally prevalent in Hib (31%) and non-b-type (29%) isolates, and in pneumonia (31%) and meningitis (34%) cases. None was resistant to amoxicillin-clavulanate, ceftriaxone, ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin. Of all H. influenzae infections, 40%, 4.4% and 100% of pneumonia, meningitis and septicemia cases were caused by other serotypes or non-typeable strains. All ampicillin-resistant-strains produced beta-lactamase without detection of beta-lactamase-negative-ampicillin-resistant (BLNAR) strains.


CONCLUSIONS
Hib is a leading cause of invasive bacterial infections in infants. Multidrug-resistant H. influenzae is common and requires amoxicillin-clavulanate, ceftriaxone or azithromycin as empirical therapy with specific recommendation for use of ceftriaxone for treatment of meningitis particularly MDR cases. New fluoroquinolines has potential utility. An effective national Hib vaccination programme is essential in Bangladesh although non-Hib infections will remain an issue.
Rahman
Mahbubur
M
International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh. mahbubur@icddrb.org
Hossain
Shahadat
S
Baqui
Abdullah Hel
AH
Shoma
Shereen
S
Rashid
Harunur
H
Nahar
Nazmun
N
Zaman
Mohammed Khalequ
MK
Khatun
Farida
F
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000097:blood / Q000134:cerebrospinal fluid; D001426:Bacterial Proteins / Q000235:genetics; D001459:Bangladesh / Q000453:epidemiology; D001769:Blood / Q000382:microbiology; D001774:Blood Chemical Analysis; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000382:microbiology; D002675:Child, Preschool; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D006192:Haemophilus Infections / Q000453:epidemiology* / Q000382:microbiology* / Q000401:mortality; D006193:Haemophilus influenzae / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification*; D019741:Haemophilus influenzae type b / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D007841:Latex Fixation Tests; D008581:Meningitis / Q000453:epidemiology / Q000382:microbiology / Q000401:mortality; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000453:epidemiology / Q000382:microbiology / Q000401:mortality; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D018805:Sepsis / Q000453:epidemiology / Q000382:microbiology / Q000401:mortality
D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C068101:bexA protein, Haemophilus influenzae