Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study

Abstract

SummaryBackgroundBacterial 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.MethodsIn 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.FindingsBetween 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.InterpretationThe 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.FundingWellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE).

Drivers of antimicrobial resistance amongst intestinalEscherichia coliisolated from children in South Asia and sub-Saharan Africa

“…The high AMR frequencies for first-line drugs, in particular penicillins, detected in this study are similar to reports of other intestinal, extra-intestinal and environmental isolates of E. coli 22,37 . Of note, the high levels of ciprofloxacin-resistance found in this study at the Asian sites corresponded to high levels reported in clinical cases in India, Bangladesh and Pakistan 17,18,21,23,24,38 . Further, while ESBL-producing aEPEC were detected in this study in Asia, the frequency of these was lower than those reported from hospitals in both Asia and Africa 18,21,31,38 .…”

“…Of note, the high levels of ciprofloxacin-resistance found in this study at the Asian sites corresponded to high levels reported in clinical cases in India, Bangladesh and Pakistan 17,18,21,23,24,38 . Further, while ESBL-producing aEPEC were detected in this study in Asia, the frequency of these was lower than those reported from hospitals in both Asia and Africa 18,21,31,38 . These findings suggest the prevalence of ESBLs, and indeed resistance to carbapenems and last-line aminoglycosides (which were not detected in these community aEPEC) are in higher circulation in hospital settings and have not yet become established in the community settings we investigated.…”

“…Of greatest concern are multi-drug resistant (MDR) E. coli (non-susceptible to one or more agents in at least three antimicrobial categories) 16 , particularly those that are fluoroquinolone resistant and/or produce extended-spectrum beta-lactamases (ESBL). While several recent studies have reported increases in ESBLs 17,18 , gentamicin 19,20 , ciprofloxacin [20][21][22][23][24] and revealed diverse AMR profiles, these data have largely come from E. coli responsible for disease in hospital settings. Thus, there remain significant gaps in knowledge of the prevalence of AMR in human intestinal E. coli populations globally, particularly in the developing nations of sub-Saharan Africa and South Asia 25 .…”

The scourge of avoidable neonatal mortality in Malawi

“…Resistance has soared, according to a surveillance study in adults and paediatric patients by the Malawi Liverpool Wellcome Centre, the research institute next to Queen Elizabeth hospital 1. Over 18 years to 2016, although the number of bloodstream infections fell, the proportion involving resistant bacteria increased, says Nicholas Feasey, an infectious diseases researcher who led the study.…”

Emerging Challenges and Opportunities in Infectious Disease Epidemiology

“…Outbreaks of severe acute respiratory syndrome, pandemic influenza A H1N1, Ebola virus (EBOV), and Zika virus have prompted international responses, whereas influenza A H7N9 and H5N1, Lassa fever virus, Nipah virus, and Middle East respiratory syndrome coronavirus, among other agents, have been a source of regional concern. The incidence and endemic range of "neglected" infections, including dengue and cholera (16,17), have expanded, and antimicrobial resistance has threatened to derail the control of tuberculosis, typhoid, malaria, gonorrhea, yaws, and invasive bacterial infections (18)(19)(20)(21)(22)(23). Although highly effective vaccines are available, measles and yellow fever have resurged on multiple continents, due to gaps in vaccine coverage (24,25), while short-lived vaccine-induced protection has facilitated unexpected resurgences in diseases once on the path to elimination, such as pertussis and mumps (26,27).…”