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孟加拉国城市地区5岁以下儿童中b型和非b型流感嗜血杆菌侵袭性疾病:对治疗和疫苗接种的启示

Haemophilus influenzae type-b and non-b-type invasive diseases in urban children (<5years) of Bangladesh: implications for therapy and vaccination.

作者信息

Rahman Mahbubur, Hossain Shahadat, Baqui Abdullah Hel, Shoma Shereen, Rashid Harunur, Nahar Nazmun, Zaman Mohammed Khalequ, Khatun Farida

机构信息

International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.

出版信息

J Infect. 2008 Mar;56(3):191-6. doi: 10.1016/j.jinf.2007.12.008.

DOI:10.1016/j.jinf.2007.12.008
PMID:18280571
Abstract

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.

CONCLUSION

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.

摘要

目的

前瞻性研究儿童侵袭性感染中流感嗜血杆菌分离株的流行病学及抗生素耐药性。

方法

纳入孟加拉国达卡三家医院的<5岁肺炎、脑膜炎和败血症患儿(1999 - 2003年);收集临床和实验室数据以及血培养样本。对脑膜炎病例的脑脊液(CSF)进行分析(革兰氏染色、培养及生化检测)。对培养阴性的化脓性脑脊液采用乳胶凝集试验(LA)检测b型流感嗜血杆菌(Hib)抗原,对培养及LA均阴性的化脓性脑脊液进行bexA基因的聚合酶链反应(PCR)检测。采用E试验测定抗生素敏感性,用硝基头孢菌素试纸条检测β - 内酰胺酶。

结果

共检测到73例流感嗜血杆菌感染(293例脑膜炎病例中的46例,1493例肺炎病例中的25例,48例败血症病例中的2例);其中分别有63%、34%和3%的病例患有脑膜炎、肺炎和败血症。b型流感嗜血杆菌(Hib)导致80.8%的病例感染(脑膜炎占60.3%,肺炎占20.5%)。大多数(86%)感染集中在4 - 12个月的婴儿。肺炎的病死率为8%,而脑膜炎为19%。肺炎和脑膜炎患儿分离出的流感嗜血杆菌对抗生素的耐药性相当(分别为46%和43%)。在检测的10种药物中,分离株对氨苄西林耐药率为31%,对氯霉素耐药率为42%,对甲氧苄啶 - 磺胺甲恶唑耐药率为44%,对阿奇霉素耐药率为1.4%。多重耐药(MDR)菌株在Hib(31%)和非b型(29%)分离株中同样普遍,在肺炎(31%)和脑膜炎(34%)病例中也同样普遍。无一例对阿莫西林 - 克拉维酸、头孢曲松、环丙沙星、左氧氟沙星、莫西沙星和加替沙星耐药。在所有流感嗜血杆菌感染中,肺炎、脑膜炎和败血症病例分别有40%、4.4%和100%由其他血清型或不可分型菌株引起。所有耐氨苄西林菌株均产生β - 内酰胺酶,未检测到β - 内酰胺酶阴性的耐氨苄西林(BLNAR)菌株。

结论

Hib是婴儿侵袭性细菌感染的主要原因。多重耐药的流感嗜血杆菌很常见,经验性治疗需要使用阿莫西林 - 克拉维酸、头孢曲松或阿奇霉素,特别推荐使用头孢曲松治疗脑膜炎,尤其是多重耐药病例。新型氟喹诺酮类药物具有潜在应用价值。在孟加拉国,有效的全国性Hib疫苗接种计划至关重要,尽管非Hib感染仍将是一个问题。

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