Musicha Patrick, Cornick Jennifer E, Bar-Zeev Naor, French Neil, Masesa Clemens, Denis Brigitte, Kennedy Neil, Mallewa Jane, Gordon Melita A, Msefula Chisomo L, Heyderman Robert S, Everett Dean B, Feasey Nicholas A
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; College of Medicine, University of Malawi, Blantyre, Malawi; Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
Lancet Infect Dis. 2017 Oct;17(10):1042-1052. doi: 10.1016/S1473-3099(17)30394-8. Epub 2017 Aug 14.
Bacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance.
In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016. The hospital served an urban population of 920 000 in 2016, with 1000 beds, although occupancy often exceeds capacity. The hospital admits about 10 000 adults and 30 000 children each year. Antimicrobial susceptibility tests were done by the disc diffusion method according to British Society of Antimicrobial Chemotherapy guidelines. We used the Cochran-Armitage test for trend to examine trends in rates of antimicrobial resistance, and negative binomial regression to examine trends in icidence of bloodstream infection over time.
Between Jan 1, 1998, and Dec 31, 2016, we isolated 29 183 pathogens from 194 539 blood cultures. Pathogen detection decreased significantly from 327·1/100 000 in 1998 to 120·2/100 000 in 2016 (p<0·0001). 13 366 (51·1%) of 26 174 bacterial isolates were resistant to the Malawian first-line antibiotics amoxicillin or penicillin, chloramphenicol, and co-trimoxazole; 68·3% of Gram-negative and 6·6% of Gram-positive pathogens. The proportions of non-Salmonella Enterobacteriaceae with extended spectrum beta-lactamase (ESBL) or fluoroquinolone resistance rose significantly after 2003 to 61·9% in 2016 (p<0·0001). Between 2003 and 2016, ESBL resistance rose from 0·7% to 30·3% in Escherichia coli, from 11·8% to 90·5% in Klebsiella spp and from 30·4% to 71·9% in other Enterobacteriaceae. Similarly, resistance to ciprofloxacin rose from 2·5% to 31·1% in E coli, from 1·7% to 70·2% in Klebsiella spp and from 5·9% to 68·8% in other Enterobacteriaceae. By contrast, more than 92·0% of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Meticillin-resistant Staphylococcus aureus (MRSA) was first reported in 1998 at 7·7% and represented 18·4% of S aureus isolates in 2016.
The rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting.
Wellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE).
在撒哈拉以南非洲地区，细菌血症是发病和死亡的常见原因，但很少有机构能够进行长期监测。自1998年以来，马拉维-利物浦-惠康信托临床研究项目一直在对菌血症进行哨点监测。我们报告了该监测中血流感染和抗菌药物耐药性的长期趋势。
在这项监测研究中，我们分析了1998年至2016年期间从马拉维布兰太尔伊丽莎白女王中央医院收治的发热或疑似脓毒症的成年和儿科患者中常规采集的血培养样本。该医院在2016年服务于92万城市人口，有1000张床位，尽管床位使用率经常超过容量。该医院每年收治约10000名成人和30000名儿童。根据英国抗菌化疗协会指南，采用纸片扩散法进行抗菌药物敏感性试验。我们使用 Cochr an-Armitage趋势检验来检查抗菌药物耐药率的趋势，并使用负二项回归来检查随时间变化的血流感染发病率趋势。
在1998年1月1日至2016年12月31日期间，我们从194539份血培养样本中分离出29183种病原体。病原体检测率从1998年的327.1/10万显著下降至2016年的120.2/10万（p<0.0001）。在26174株细菌分离株中，13366株（51.1%）对马拉维一线抗生素阿莫西林或青霉素、氯霉素和复方新诺明耐药；革兰阴性病原体中68.3%耐药，革兰阳性病原体中6.6%耐药。2003年后，产超广谱β-内酰胺酶（ESBL）或耐氟喹诺酮的非沙门氏菌属肠杆菌科细菌比例显著上升，2016年达到61.9%（p<0.0001）。2003年至2016年期间，大肠杆菌中ESBL耐药率从0.7%升至30.3%，克雷伯菌属从11.8%升至90.5%，其他肠杆菌科细菌从30.4%升至71.9%。同样，大肠杆菌对环丙沙星的耐药率从2.5%升至31.1%，克雷伯菌属从1/7%升至70.2%，其他肠杆菌科细菌从5.9%升至68.8%。相比之下，超过92.0%的常见革兰阳性病原体对青霉素或氯霉素仍敏感。耐甲氧西林金黄色葡萄球菌（MRSA）于1998年首次报告，占比7.7%，2016年占金黄色葡萄球菌分离株的18.4%。
常见革兰阴性病原体中ESBL和氟喹诺酮耐药性的迅速增加以及MRSA的出现，凸显了在这种资源有限的环境中有效治疗血流感染日益严峻的挑战。
惠康信托基金、H3ABionet、南部非洲卓越研究联盟（SACORE）。
