Series

Sustainable Access to Antibiotics 1

The scope of the antimicrobial resistance challenge
Iruka N Okeke, Marlieke E A de Kraker, Thomas P Van Boeckel, Chirag K Kumar, Heike Schmitt, Ana C Gales, Silvia Bertagnolio, Mike Sharland,
Ramanan Laxminarayan

Each year, an estimated 7·7 million deaths are attributed to bacterial infections, of which 4.95 million are associated Published Online
with drug-resistant pathogens, and 1·27 million are caused by bacterial pathogens resistant to the antibiotics available. May 23, 2024
https://doi.org/10.1016/
Access to effective antibiotics when indicated prolongs life, reduces disability, reduces health-care expenses, and
S0140-6736(24)00876-6
enables access to other life-saving medical innovations. Antimicrobial resistance undoes these benefits and is a major
See Online/Comment
barrier to attainment of the Sustainable Development Goals, including targets for newborn survival, progress on https://doi.org/10.1016/
healthy ageing, and alleviation of poverty. Adverse consequences from antimicrobial resistance are seen across the S0140-6736(24)01030-4
human life course in both health-care-associated and community-associated infections, as well as in animals and the See Online/Perspectives
food chain. The small set of effective antibiotics has narrowed, especially in resource-poor settings, and people who https://doi.org/10.1016/S
are very young, very old, and severely ill are particularly susceptible to resistant infections. This paper, the first in a 0140-6736(24)01034-1

Series on the challenge of antimicrobial resistance, considers the global scope of the problem and how it should be This is the first in a Series of four
papers on sustainable access to
measured. Robust and actionable data are needed to drive changes and inform effective interventions to contain antibiotics. All papers in the
resistance. Surveillance must cover all geographical regions, minimise biases towards hospital-derived data, and Series can be found at thelancet.
include non-human niches. com/series/antibiotic-resistance
Department of Pharmaceutical
Introduction decreasing likelihood of being able to access effective Microbiology, Faculty of
Pharmacy, University of
As many as 1·27 million of the 7·7 million estimated treatments. Infections from resistant bacteria are a
Ibadan, Ibadan, Nigeria
deaths attributable to bacterial infections could be caused health concern comparable to, if not potentially greater (Prof I N Okeke PhD); Infection
by bacterial pathogens resistant to the antibiotics than, HIV and malaria and affect all regions of the world Control Program, Geneva
available to treat them.1,2 This untenably high burden University Hospitals and
Faculty of Medicine, Geneva,
from antimicrobial resistance (AMR) keeps growing.3–5 Key messages Switzerland
Yet AMR is typically presented as a discreet problem and (M E A de Kraker PhD); WHO
thus is invisible to many stakeholders. AMR currently • Antimicrobial resistance, specifically antibiotic resistance, is Collaborating Centre on AMR,
affects the health, wellbeing, and potential of most compromising health and development targets, including Geneva, Switzerland

humans and other species that inhabit the world. Today, the UN’s Sustainable Development Goals; this puts not just (M E A de Kraker); Health
Geography and Policy Group,
humans begin and end life with a substantial probability vulnerable individuals, such as neonates, older people and
Department of Environmental
of contracting an antimicrobial-resistant infection and a the chronically ill, but entire health systems at risk. Systems Science, ETH Zürich,
• Increases in resistance among bacterial pathogens in Zürich, Switzerland
humans, animals, the food chain, and the environment (T P Van Boeckel PhD); One
Health Trust, Bengaluru, India
Search strategy and selection criteria have been documented in the past two decades.
(T P Van Boeckel, C K Kumar BA,
• Progress in treating non-communicable diseases, Prof R Laxminarayan PhD);
38 experts in antimicrobial resistance and global health
including diabetes and cancer, in people of all ages is Centre for Zoonoses and
reviewed Sustainable Development Goal targets, the current Environmental Microbiology,
threatened by antimicrobial resistance.
state of data availability, and then elected the following focal Dutch National Institute for
• Antibiotic use in medicine and agriculture, the selective
areas for in-depth review: neonatal sepsis, health-care- Public Health and the
force for resistance, is insufficiently documented, as are Environment (RIVM),
associated infection, typhoid, gonorrhoea, and
resistance rates, trends, and burden. Bilthoven, Netherlands
pneumococcal infection (tuberculosis was excluded). (Prof H Schmitt PhD);
• Diagnostics that determine when and which antibiotics
MEDLINE was searched via PubMed for relevant review Environmental Biotechnology,
are needed will enhance patient care and inform the
articles from January, 2003 to June, 2023 about antimicrobial Faculty of Applied Sciences,
public health response. Delft University of Technology,
or antibiotic resistance or antimicrobial or antibiotic
• Resistant bacteria are disseminated by humans and non- Delft, Netherlands
consumption. Papers cited in the reviews were selected from (Prof H Schmitt); Division of
human and inanimate intermediaries, including health-
the reference lists. Supporting data for the focal areas were Infectious Diseases, Paulista
care apparatus. The resistant microbial lineages can
retrieved from the following publicly available curated School of Medicine, Federal
become entrenched in health-care facilities, in the University of São Paulo
resistance databases or sources: the 2019 GBD study and
community, and across food chains. Unless detected (EPM-UNIFESP), São Paulo,
2019 GRAM project, NeoOBS, CHAMPS, BARNARDS, the Brazil (Prof A C Gales MD PhD);
quickly and stopped through infection prevention and
DeNIS study, ResistanceMap, ResistanceBank, Department of Surveillance,
control, these lineages can spread in facilities across the
PathogenWatch, Typhinet, and the Medicine Quality Control, and Prevention of
world, endangering millions. Antimicrobial Resistance,
Scientific Literature Surveyor. The expert group additionally
• Every country needs a surveillance system to track antibiotic WHO, Geneva, Switzerland
listed relevant policy documents associated with the WHO (S Bertagnolio MD); Centre for
use and resistance and to evaluate interventions.
Global Action Plan for Antimicrobial Resistance. Neonatal and Paediatric

www.thelancet.com Published online May 23, 2024 https://doi.org/10.1016/S0140-6736(24)00876-6 1

 Series

Infection, St George’s,
University London, London, UK Panel 1: Trends in the burden of AMR
(Prof M Sharland MD); High
Meadows Environmental AMR in humans ischaemic heart disease, stroke, and chronic obstructive
Institute, Princeton University, AMR trend analyses point to a rise in resistant infections, pulmonary disease. In addition to absolute AMR rates, the
Princeton, NJ, USA notably in Gram-negative organisms, in the past decade.6 burden from resistance is driven by the overall infectious
(Prof R Laxminarayan)
In Europe in 2019–21, increasing rates of resistance were disease burden and access to second-line and reserve
Correspondence to:
reported, particularly carbapenem-resistant Acinetobacter spp antimicrobials that can be used to treat resistant infections.
Dr Iruka N Okeke, Department of
Pharmaceutical Microbiology, causing bloodstream infections in 2017–21.7 The substantial Thus, the estimated all-age death rate attributable to resistance
Faculty of Pharmacy, University estimated burden of resistant infections in Europe increased was highest in west Africa (27·3 deaths per 100 000 people) and
of Ibadan, between 2007 and 2015.8 In 2015, the 426 277 antimicrobial- lowest in Australasia (6·5 deaths per 100 000 people). Such
Ibadan 200284, Nigeria
resistant HCAIs accounted for an estimated 33 110 attributable estimates have several limitations: the data come from a small
[email protected]
deaths and 874 541 DALYs.8 Projections from high-income number of countries; DALYs did not account for prolonged
or
countries predict a 2·1-times rise in resistance to third-line treatment effects, disability, or other sequelae; and burden
Prof Ramanan Laxminarayan,
One Health Trust,
antimicrobials—the last-resort drugs—by 2035 compared estimates included non-hospitalised patients, but pathogen
Bengaluru 560042, India with 2005. distributions and case fatality ratios were derived from hospital
[email protected]
The Global Research on Antimicrobial Resistance study data. Furthermore, due to sparse data, resistance proportions
For the GRAM project see
estimated that 4·95 million (95% CI 3·62–6·57 million) deaths and relative risks were assumed equal across subpopulations,
https://www.tropicalmedicine. infection sites, and locations, affecting the reliability of the
ox.ac.uk/gram were associated with bacterial AMR in 2019 (ie, the patient died
with a bacterial AMR infection that might or might not have rankings.
For NeoOBS see https://penta-
id.org/severe-infections-and- been the cause of death), including 1·27 million The appendix (pp 7-8) has information on the burden of AMR
antimicrobial-resistance/neoobs/ (0·91–1·71 million) deaths attributable to bacterial AMR (ie, the in domesticated animals.
For CHAMPS see https:// patient likely died of a bacterial AMR infection).1 The upper limit
champshealth.org/ AMR=antimicrobial resistance. DALY=disability-adjusted life-year. HCAI=health-care-
would place AMR in the top three causes of death, after acquired infection. LMIC=low-income and middle-income country.

A B C (panel 1).1 AMR threatens infectious disease management

Category at all ages and constrains medical progress.
Neonatal sepsis In children younger than 5 years, a drastic decline in
Neonatal all-cause mortality
<5 years all-cause mortality deaths (as much as 50% between 2000 and 2013) was
Neonatal mortality if no AMR achieved through improvements in water and sanitation,
<5 years mortality if no AMR
vaccination, and other public health interventions.9
100 100 Age group 100 Age
Neonates ≥65 years However, Sustainable Development Goal 3 (ie, to ensure
20
Bacteria-attributable mortality rate

<5 years <65 years healthy lives and promote wellbeing at all ages and to
Mortality rate relative to 2000, %

80 reduce newborn mortality to less than 12 deaths

Estimated change from

relative to 2000, %

80
2010 to 2020, %

10 per 1000 livebirths by 2030) is jeopardised when antibiotics

60
do not work, resistant organisms are disseminated, or
0 patients cannot access the medicines they require
60 (figure 1). A third of newborn deaths are attributable to
40 SDG neonatal mortality target infection and half of those to sepsis14 and, increasingly, the
–10
SDG under five mortality target pathogens no longer respond to the most readily available
20 40 antibiotics.
MDR Overall At the other end of life, the comorbidities and
10

10
20

20
00

00
05

05
15

15
20

20
20

20
20

20
20

20

20

20

Year
Sepsis isolates
Year
immunosenescence that can accompany ageing
aggravate the propensity for infection—increasingly,
Figure 1: AMR delays progress towards global childhood survival targets antimicrobial-resistant infection (figure 2). Roughly a
(A) Progress in reducing mortality in children younger than 5 years, neonatal mortality, and neonatal sepsis tenth of the world’s population is older than 65 years, a
since 2000 in comparison with the SDG targets for mortality in neonates and children younger than 5 years.
Dashed lines present a counterfactual scenario were there to be no AMR-attributable deaths (see appendix p 3 for proportion likely to double by 2050.16 Additionally,
details); the shift from the reported values is based on the Global Burden of Disease Antimicrobial Resistance study1 progress in treating non-communicable diseases (NCDs),
and the rate of change is calculated from cohort studies on AMR.10–12 (B) Reported percent changes in the past including diabetes and cancer, in people of all ages is
decade of neonatal sepsis isolates by drug resistance. Source data is the same as that for the counterfactual
constrained by AMR. For example, 26·8% of the
scenario of no AMR in the first panel. MDR is defined akin to Sievert and colleagues13 to mean drug resistance to a
majority of the currently prescribed antibiotic treatments at the time of data analysis. (C) Progress in reducing pathogens causing infections in patients with blood
bacterial mortality since 2000 for people aged 65 years and older compared with people younger than 65 years. To cancer and undergoing chemotherapy are resistant to
obtain estimates of bacteria-attributable mortality, all Global Burden of Disease syndromic causes that have antimicrobials used for infection prophylaxis.17 Drug-
bacterial underpinnings are summed for the two age groups. AMR=antimicrobial resistance. MDR=multidrug
resistant health-care-acquired infections (HCAIs) in
resistance. SDG=sustainable development goal.
such patients complicate treatment and survival,
lengthen hospital stays, and increase cost of care.

2 www.thelancet.com Published online May 23, 2024 https://doi.org/10.1016/S0140-6736(24)00876-6

 Series

For BARNARDS see https://

A B www.cardiff.ac.uk/research/
140000 Pathogen 100 explore/research-units/burden-
Other
of-antibiotic-resistance-in-
Acinetobacter baumanii
AMR-attributable deaths in people ≥65 years

120000 12 neonates-from-developing-

All-cause mortality in people ≥65 years, %

Escherichia coli
Klebsiella pneumoniae societies-barnards
100000 Staphylococcus aureus 10 For ResistanceMap see https://
Streptococcus pneumoniae
resistancemap.onehealthtrust.
Pseudomonas aeruginosa
80000 8 org
For ResistanceBank see https://
60000 6 resistancebank.org
For PathogenWatch see https://
40000 4 pathogen.watch
For Typhinet see https://www.
20000 2 typhi.net
For the Medicine Quality
0 0
Scientific Literature Surveyor

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Region Region item/9789241509763

Figure 2: Drug-resistant infections present a substantial burden on ageing populations See Online for appendix
(A) Estimated number of AMR-attributable deaths (ie, infection from a drug-resistant pathogen that is in the causal chain of death) stratified by the top five
pathogens among individuals older than 65 years. The height of the bars represents the total number of all-cause deaths that are attributable to an AMR pathogen
and the coloured section of each bar represents the contribution of each pathogen. Data are shown by geographical GBD super region. (B) Percentage of all-cause
mortality in people older than 65 years that are attributable to AMR by pathogen. Source data on the burden of AMR pathogens are from the GRAM study,1 and
estimates for the total number of all-cause deaths in people older than 65 years for scaling in (B) are from the GBD study.15 Estimates reflect the situation as of 2019.

AMR also threatens global health through food monitoring their NAPs; LMICs in particular face
insecurity as it restricts our ability to treat sick livestock. substantial barriers.
Overuse of antibiotics on farms and discharge of active This 2024 Lancet Series on sustainable access to
antimicrobials into the environment select for resistant effective antimicrobials presents initiatives and targets to
bacterial lineages in those settings and place humans tackle the global threat to health of AMR. This is the first
and animals at risk of a future pandemic from an paper in this Series and examines how AMR and
untreatable bacterial infection.18,19 AMR is thus a antibiotic use have intersected with disease burden over
One Health challenge that requires surveillance and the past decade and the need for improved surveillance.
interventions across human, animal, and environmental The second paper in the Series models the effectiveness
domains. of interventions to stop the rise of, or reduce, AMR in
Drivers of resistance in both humans and animals resource-limited settings.21 The third paper in the Series
include antibiotic use and insufficient application of examines how research and development can address
preventive measures (eg, poor access to water and AMR.22 The fourth paper in the Series proposes
sanitation, insufficient vaccination, and failure of achievable targets for a 10% reduction in disease burden
infection prevention in health-care facilities). from AMR by 2030.23
In the past decade, many countries have created Here, we present evidence on the growing effect of
national action plans (NAPs) on how they plan to address AMR on global health and examine options for
antimicrobial resistance. Most of these NAPs are pragmatic, rapid improvements in global AMR and
modelled on the WHO Global Action Plan20 and surveillance of antibiotic use. Our aim in this paper, and
emphasise the importance of increasing awareness of throughout the Series, is to present the problem of AMR
AMR among health workers and the general public, as a horizontal or cross-cutting one that is exacerbated by
carrying out surveillance to quantify the problem, inequitable access to antimicrobials. Our scope is
preventing infections and the dissemination of restricted to non-tuberculosis bacterial and fungal
antimicrobial-resistant bacteria, researching and pathogens, although drug resistance is a growing
developing new antimicrobials, and other strategies for impediment to the treatment of tuberculosis, malaria,
overcoming or avoiding resistance, as well as highlighting HIV infection, and other infections. We begin by
the economic benefits of strategies to address AMR. outlining the challenge posed by AMR to global goals for For the WHO factsheet on
antimicrobial resistance see
According to a WHO factsheet, 178 countries have child survival, healthy ageing, and food security. We https://www.who.int/news-
developed NAPs on AMR as of November, 2023, and of review the state of AMR in infections caused by room/fact-sheets/detail/
those, only 25% are effectively implementing and community-acquired pathogens that infect people across antimicrobial-resistance

www.thelancet.com Published online May 23, 2024 https://doi.org/10.1016/S0140-6736(24)00876-6 3

 Series

the courses of their lives, depending on exposure and in a South African neonatal unit has involved 91 cases
risk. We then summarise progress and gaps in measuring over 4 years.35
and reporting of AMR and antimicrobial use, and we Identification of causative bacteria and antimicrobial
propose suggestions for improving surveillance. susceptibility information are crucial to managing sepsis
and to identifying outbreaks. These data, generated in
AMR in health-care settings health-care facilities, can feed into local, national, and
Threats to newborn survival regional surveillance at little extra cost. For neonatal sepsis
AMR prevents the achievement of multiple health- and other infections caused by blood-borne bacteria,
related targets. For example, neonatal sepsis remains a pathogen information derives from blood cultures, which
global concern, as the eighth most common cause of have a low yield (typically <20%) and a high contamination
death in neonates and children younger than 5 years, rate (perhaps >10% in low-resource settings).36 Because
with high rates in low-resource settings.24,25 Babies with blood culture sampling is most challenging in neonates,
early onset sepsis might be infected before or during contamination rates can be higher than the institutional
birth because of premature rupture of maternal average. Deep molecular diagnostics, such as
membranes; late onset (age 3–28 days) sepsis commonly metagenomic approaches, can yield a causative agent in
represents a HCAI. Outbreaks of resistant bacteria almost 4 times as many cases, but cost currently precludes
attributable to poor infection prevention and control are their routine use.27,30 Genomic enrichment methods and
increasingly detected in neonatal sepsis, often only point-of-care aetiological tests are promising but are still
retrospectively. Babies born at a health facility can benefit under development. In high-income settings, a neonate
from emergency obstetric or newborn care,13 but HCAIs with suspected sepsis typically undergoes more than
could stall or reverse such child survival gains. one blood culture and supporting tests to confirm the
AMR constrains neonatal sepsis management: in a diagnosis and guide care. The current goal for low-
study across 11 countries, 18% of babies who had resource settings is that blood culture testing be available
pathogen-positive blood cultures did not survive despite at referral centres,37 but even there, the required
receiving empirical antimicrobial therapy.26 Similar infrastructure, consumables, skilled personnel, and
neonatal sepsis outcomes due to resistance to first-line quality management systems are often missing, and thus
empirical treatment regimens recommended by WHO very few infections are cultured.38,39 National and regional
have been reported elsewhere in the past two decades.27,28 surveillance networks built around existing blood culture
Overall, an estimated 214 000 neonatal deaths globally machines largely consist of tertiary sentinels, where
were attributed to antimicrobial-resistant neonatal sepsis resistance patterns of opportunistic pathogens differ
each year a decade ago.1,29 Klebsiella (particularly markedly from primary-care and secondary-care isolates,
pneumoniae), Staphylococcus, Acinetobacter, and limiting the actionability of the data.27
Escherichia spp are the most common causes of neonatal Surveillance is increasingly uncovering outbreaks in
sepsis (not necessarily in that order), particularly in low- neonatal intensive-care units.40,41 Applying whole-genome
resource settings.1,27,28,30,31 In addition, maternally acquired sequencing, which will ultimately support tools to
Streptococcus agalactiae is a common cause of early-onset prevent mortality (see the third paper in this Series22),
neonatal sepsis in high-income settings.11,26,30 Real and permits fine-level tracking of the opportunistic causes of
perceived risk of mortality due to resistant bacteria neonatal sepsis, revealing routes through which bacteria
causing sepsis has prompted overuse of carbapenem are transmitted, whether directly among patients or via
antibiotics and a consequent increase in rates of intermediaries, including medical devices and parenteral
carbapenem resistance. Clinicians increasingly need to medications.35,42,43 Whole-genome sequencing has
use last-resort drugs like colistin,26 which has more (and revealed that specific lineages of Escherichia coli
more serious) adverse effects than first-line, second-line, (eg, sequence types 69, 73, 95, and 131) and K pneumoniae
and third-line empirical drugs and whose long-term (eg, sequence types 11, 15, and 17)44,45 are over-represented
effects for neonates are largely uncertain. in neonatal sepsis and HCAIs.11,46 A maternal vaccination
Neonatal sepsis is most commonly secondary to a strategy targeting these lineages could significantly
systemic bacterial infection, but fungal infections can lower neonatal sepsis rates.47 Surveillance through
also initiate sepsis, particularly in infants with low whole-genome sequencing provides lineage and antigen
birthweights. Sepsis following fungal infection occurs information at no extra cost and offers more granularity
worldwide but is best documented in high-income than earlier genotypic methods; however, it does not yet
settings.27,32 Candida albicans and Candida parapsilosis are achieve predictiveness to consistently guide empirical
common causes, but since 2009, Candida auris is of even prescriptions or prevent HCAIs. Because turnaround
greater concern.33 C auris isolates are typically resistant to times are typically long, few outbreaks have been
most or all known antifungals, infections have high shortened, stopped, or shrunk by sequencing. A short
mortality rates, and the organism was labelled critical on turnaround has been achieved in some instances;42 the
the 2022 WHO Fungal Priority Pathogens List.34 A barriers to the full potential of genomic surveillance
possibly ongoing fluconazole-resistant C auris outbreak arise from its use in large flagship initiatives too far

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removed from patients at risk of antimicrobial-resistant baumannii, Pseudomonas aeruginosa, and Enterobacter spp)
infections. Facility-based genomic surveillance of are frequent HCAIs in patients with cancer.56,59 Among
neonatal intensive-care wards can help prevent patients with cancer in Spain, Bodro and collaborators
infections by identifying and segregating infants reported increased persistence of bacteraemia
colonised with potentially resistant pathogens, (25% vs 10%), metastatic infection (8% vs 4%), and early
monitoring them for sepsis, and administering case-fatality rates (23% vs 11%) for infections caused by
treatment on the basis of actual susceptibility profiles. antimicrobial-resistant ESKAPE pathogens, compared
with other, antimicrobial-susceptible pathogens.60 Patients
Threats to older people and people with chronic with infections caused by multidrug-resistant Gram-
illnesses negative bacteria, especially non-fermentative bacteria
People of any age can contract HCAIs, but people older such as Acinetobacter spp, have particularly early mortality
than 65 years face substantial risk due to rates.61,62
immunosonesence, comorbidities, and frequent or To estimate the potential effect of AMR on the efficacy
protracted interactions with health care or assisted living, of antibiotic prophylaxis across a range of surgeries and
as ageing populations benefit from advancements in cancer treatments,17 researchers modelled a
medical care. The UK National Health Service alone 30% reduction in the effectiveness of antibiotic
spends approximately £2 billion annually on HCAIs,48 prophylaxis and projected that an additional
mostly bacterial but increasingly fungal.34 HCAIs can be 6367 infection-related deaths could occur annually in
acquired at any age but are most frequent among older the USA, primarily among patients undergoing colorectal
people. Despite some improvements in infection surgery (4586 additional deaths), blood cancer
prevention and control, treatment costs continue to rise. chemotherapy (683 additional deaths), and total hip
Drug resistance prolongs the need for infection replacement (376 additional deaths).17 In the USA,
management, requires more expensive medicines, and declines in the efficacy of antibiotic prophylaxis in
threatens patients lives.49 Resistance is also a barrier to preventing surgical site infections following colorectal
surgical care, directly affecting surgical outcomes. surgery have been reported.63
Evidence suggests that some surgeries, particularly at
older ages, are deemed too risky given the likelihood of AMR in community settings
contracting an untreatable infection. The vast majority of AMR infections are acquired in the
AMR also undermines the treatment of chronic community across most of the life course.1 Community-
illnesses across the life course, putting at risk the acquired urinary tract infections (UTIs) affected more
effectiveness and value of organ transplantations, joint than 404·6 million people globally and led to nearly
replacements, cancer chemotherapy, and treatment of 236 800 deaths in 2019.64 UTIs are the most common
NCDs, which account for 80% of deaths and 70% of indication for antibiotic prescription in pregnancy,65
disability-adjusted life-years globally.50 Sub-optimally when the range of antibiotics that can be safely
managed NCDs are poorly quantified but could be a administered narrows, and are associated with maternal
substantial burden of AMR.51 AMR complicates treatment pre-eclampsia, low birthweight, and preterm birth if
for chronic kidney disease,52 diabetes and associated improperly treated.25 Although E coli is the most frequent
urinary tract and foot infections,53 chronic obstructive urinary tract pathogen in both community and hospital
pulmonary disease,54 and liver cirrhosis.55 Sepsis settings, ESKAPE pathogens are important UTI causes
following HCAI in patients being treated for NCDs as well.66,67 Community-acquired UTIs are commonly
urgently requires improved surveillance to detect caused by resistant E coli, K pneumoniae, Proteus mirabilis,
bacterial resistance outbreaks and to inform vaccine and Staphylococcus saprophyticus.66,67 Extended-spectrum
development and other prevention strategies. β-lactamase producers, such as CTX-M-15-producing
Cancer patients have a particularly high risk of infection. E coli ST131 strains, are globally disseminated and
Cancer itself can lead to malnutrition and psychological resistant to multiple antimicrobials.68,69 In some regions,
stress. Cancer treatments (including invasive medical community-acquired UTIs caused by carbapenemase-
devices, surgery, chemotherapy, radiation, immunotherapy) producing E coli increasingly necessitate intravenous
can also increase the risk of infection.56,57 In a retrospective antibiotics.70,71
study, the mortality rate due to fatal infection in US cancer
patients was 260·1 per 100 000 person-years, nearly 3 times Sexually transmitted infections
that of the general population.58 In that cohort, patients Sexually transmitted bacteria cause considerable
aged 20–39 years or those older than 80 years, as well as morbidity. The stigma associated with these infections,
those receiving chemotherapy, showed a higher risk of along with few diagnostic resources, limits access to care
fatal infections.58 Antibiotic use to prevent infection in and contributes to disease spread. In 2020, an estimated
cancer patients can then select for resistant infections.17 The 82 million people contracted gonorrhoea worldwide.72
most resistant ESKAPE pathogens (Enterococcus faecium, The incidence in middle-income settings is estimated to
Staphylococcus aureus, K pneumoniae, Acinetobacter be 2 times as high and in sub-Saharan Africa, 5 times as

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high as the global average.73 In high-income settings, support treatment and sanitation priorities but also
gonorrhoea infection rates have increased drastically in identify transmission chains and guide deployment of
the past two decades, largely among men who have sex typhoid conjugate vaccine (see the second paper in this
with men—the demographic for which concerns about Series21). Genomic surveillance has identified major
AMR are greatest.74–76 Resistant Neisseria gonorrheae S Typhi clones and their routes of local and global
clones rapidly spread rapidly because of high dissemination,92,93 including locations where drug-sensitive
transmission rates and strong selection arising from lineages continue to circulate. S Typhi genomic
empirical antibiotic use.77–79 Patients with suspected surveillance is based on large numbers of genomes (with
gonorrhoea typically receive empirical treatment, often disproportionately fewer from Africa) and allows non-
from unlicenced providers in settings with weak experts to contribute and interpret genomic information.93–95
regulation.80 Surveillance is inhibited by its dependence on blood
Rational gonorrhoea treatment consists of single doses cultures, which are expensive, uncommon in many
or short courses of antibiotics known to be active against endemic areas, and insufficiently sensitive to detect most
95% or more of sentinel surveillance isolates.81 Culture and typhoid cases.96 Nevertheless, surveillance preceded
susceptibility tests take several days, and access to testing adoption of the typhoid conjugative vaccines in all but one
is very scarce because N gonorrheae requires specialised (ie, Liberia) of the countries that started immunisation
methods. The diagnosis and susceptibility profile would by 2023 (ie, Liberia, Malawi, Nepal, Pakistan, Samoa, and
ideally be confirmed in a single health-care visit so that Zimbabwe).97 Neighbouring countries commonly have
appropriate treatment could begin immediately. Today, little or no typhoid surveillance.
nucleic-acid-based tests can guide therapy, but only where In contrast to S Typhi, good genomic surveillance
technical and human capacity is available.82 Currently, resources exist for S pneumoniae, a community-acquired
patients with gonorrhoea receive ceftriaxone alone or with cause of childhood illness and mortality that is also
azithromycin, which is effective for most patients.74,76 If vaccine preventable. In 2009, an estimated
approved, zoliflodacin, which has been trialled over the 0·6 million deaths were associated with antimicrobial-
past few years, could offer a reserve option for resistant resistant S pneumoniae.1 Isolates can be retrieved from
infections.83 Mathematical modelling shows that the use of nasal-swab surveys in healthy populations and added to
rapid tests to screen for susceptibility to largely information from blood and cerebrospinal fluid
discontinued tetracycline and ciprofloxacin (seen in almost cultures,98 compensating for the poor access to
70% of isolates in some settings) could, in addition to microbiology resources. Surveying for S pneumoniae
reducing the cost of treatment, prolong the usable lifespan carriage in healthy individuals in turn makes it possible
of new drugs.84 Prevention of gonorrhoea infection reduces to obtain lineage-specific information that can inform
treatment demand. Sexually transmitted infections are vaccine deployment and empirical treatment.
best prevented with behavioural interventions, and For typhoid and other infections without easily
gonorrhoeal vaccines in development offer additional accessible pathogenic or potentially pathogenic isolates,
promise.85,86 emerging surveillance approaches (including direct
specimen testing and environmental surveillance) offer
Typhoid and Streptococcus pneumoniae infection promise. Monitoring of drug resistance and identifying
Typhoid fever is a life-threatening bloodstream infection resistance mechanisms need to be built into the new
caused by the Typhi serovariety of Salmonella enterica approaches, even at additional cost.
subspecies enterica, a faeco-orally transmitted bacterium
that only infects humans. Untreated or improperly treated Antimicrobial use: a key driver of resistance
infections are commonly fatal: 10–20% of people infected Antimicrobials cure infections but also drive resistance
with S Typhi before the antibiotic era died.87 With little shift by providing resistant microbes with a selective advantage
in incidence, antimicrobials dropped the mortality from over sensitive ones. Global antimicrobial use (AMU)—
typhoid fever to less than 1% in endemic regions.87 That the key driver of resistance—surged by 46% over the past
success in typhoid control has been reversed by rapidly two decades.99 Nevertheless, the 2016 Lancet AMR Series
evolving resistance to every broad-spectrum antimicrobial observed that more deaths were due to poor access to
treatment option that has been used (appendix p 10). antibiotics than to resistance.29 Although more patients
Typhoid is largely imported to Europe and North America now have access to antimicrobial drugs, resistance has
by returning travellers but remains a major cause of febrile made previously useful antimicrobials less effective and
illness in parts of Africa and Asia with poor sanitation.88 access to previously second-line drugs has thus become
Prevention is crucial because antibiotics treat infections more important. For example, affordable and safe
but do not control transmission.88–90 After accounting for antimicrobials (ie, antibiotics on WHO’s Access list in the
location, outbreaks attributable to multidrug-resistant AWARE classification;100 panel 2) were the mainstay of
strains are increasingly common and typically larger than neonatal infection management in the mid-to-late
outbreaks caused by antimicrobial-sensitive S Typhi.91 20th century. The close-to and actual last-resort options
Surveillance in typhoid-endemic areas would not only (ie, antiobiotics on WHO’s Watch list and Reserve list) are

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increasingly used today. Most pathogens isolated from

19 facilities in a multicountry study26 were resistant to Panel 2: AWARE—a traffic light approach to antibiotic use
antibiotics on the Access list. More than a third (37%) of In 2017, WHO developed the AWARE system for categorising
neonates started on regimens from the Watch list and the more than 250 antibiotics used in humans according to
25% of infants started on regimens from the Access or their clinical efficacy, safety, selection on resistance or effect
Watch lists had to be escalated from Access to Watch or on microbiome, and cost. Antibiotics on the Access list
from Watch to Reserve antimicrobials within 24 hours (eg, amoxicillin) are generally older, often narrow-spectrum
because their condition deteriorated or laboratory results drugs that are still effective in treating common infections,
indicated resistance. Thus, currently recommended particularly in primary care. These antibiotics have a good
neonatal sepsis regimens are commonly ineffective or safety profile and are inexpensive (where widely available).
undereffective empirical treatments because of resistance Watch antibiotics (eg, third-generation cephalosporins) have
(appendix pp 5–6). a broad spectrum of activity against resistant organisms, are
Since 2016, the World Organisation for Animal Health still widely effective against more severe infections in
has collected data on antibiotic sales for livestock from hospitals, generally are more likely to select for resistance,
more than 150 countries. Because the reporting countries and typically have higher toxicity and higher cost. Reserve
are not specified and the national reports are aggregated antibiotics (eg, colistin) are used as a last resort to treat
by region (ie, Europe, Africa, Americas, Middle East, and multidrug-resistant infections in severely ill patients. The
Asia–Far East–Oceania), the effect of national policies on WHO Essential Medicines List includes about 30 antibiotics
AMU cannot be determined. Moreover, one country’s on the Access and Watch lists and 10 in the Reserve list.
success in reducing AMU is diluted at the regional level In 2019, WHO added a Not Recommended category of
if usage rises in neighbouring countries. Between 2016 antibiotics, mainly inappropriate fixed-dose combinations.
and 2018, the World Organisation for Animal Health
The WHO 2022 AWARE book guides on the optimal choice of
reported a decline in global AMU from
drug, dose, and duration for about 35 common infections in
92 269 to 69 455 tonnes, which was largely attributable to
adults and children in primary care and hospital settings, with
China (where consumption fell from
a strong focus on universal health care.100 The
44 186 to 29 774 tonnes). Modelling estimates of national-
recommendations now underpin the development of future
level AMU attempt to overcome such limitations.
policy goals. For example, antibiotics on the Access list (most
For 2020, one estimate named China, Brazil, India, and
commonly amoxicillin) are the first-choice recommendation
the USA as the top four countries for absolute AMU,
for 90% of the most common infections seen in primary care.
measured in tonnes.101 From 2017 to 2020, AMU in pigs
The AWARE book also takes a risk-based approach, giving
fell slightly (from 193 to 173 mg per Population Correction
guidance on when an antibiotic is not recommended, usually
Unit), but in poultry this measure fell sharply (from
for minor respiratory infections. AWARE-based quality
68 to 35 mg per Population Correction Unit) despite
indicators, quality metrics, and educational and stewardship
continued growth of the poultry sector.
interventions have been developed. The AWARE system’s
AMU estimates assume that claims on medication
traffic light approach has simplified surveillance and
labels of active ingredients are accurate, but an estimated
monitoring of antibiotic use and will dictate in the future
10% of antimicrobials marketed in LMICs are
which Access antibiotics should be universally available to
substandard or falsified.102 Medicines can contain less (or
meet Sustainable Development Goal 3.8 (ie, achieving
sometimes more) than the labelled amount. Antibiotics
universal health coverage). Many older antibiotics on the
can be incorrectly transported and stored, leading
Watch list with little usefulness are still widely produced, and
(particularly in the tropics) to physical and chemical
further guidance on unnecessary antibiotics is needed.
degradation that affects shelf life and therefore
Developing policy goals on the basis of absolute amounts of
effectiveness. Falsified antimicrobials are particularly
Access, Watch, and Reserve antibiotics at a country level will
common when regulation and supply chains are weak
require risk adjustment for burden of disease, demography,
and infection burdens (and therefore demand) are high.
mortality, and rates of AMR.
The Medicine Quality Scientific Literature Surveyor For the Medicine Quality
finds that substandard antibiotics are commonly reported AMR=antimicrobial resistance. AWARE=Access, Watch, Reserve. Scientific Literature Surveyor
see https://www.iddo.org/
from west and east Africa, south and east Asia, and mqsurveyor/
central America. Besides confounding consumption
estimates, substandard medicines could exacerbate difficulties of documentation (appendix p 9), AMU in
selection for AMR even when used according to human clinical medicine, veterinary medicine, and
prescription through various mechanisms.102,103 agriculture is grossly under-reported.
Substandard or falsified antimicrobials also undermine
the resistance-thwarting goals of combination regimens, The need for antimicrobial resistance
and formulations containing no active ingredient or the surveillance
wrong active ingredient can generate false impressions The fourth paper in this Series proposes ambitious but
of resistance.Overall, because of inertia and the achievable targets for containing AMR.23 These targets

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from routine testing of patients in health-care facilities,

Panel 3: Pathways to more actionable AMR surveillance has obvious drawbacks: the data typically reflect the
The first step in designing an actionable AMR surveillance is to define the objectives and conditions of a selected sample of patients accessing
target population. Complementary data sources that do not rely on the availability of health services and diagnostics (often from tertiary-care
microbiology capacity could allow rapid and affordable geographical characterisation and facilities where resistance rates can be high) and
tracking of AMR, help strengthen surveillance of AMR, and expedite the scientific basis to resistance patterns are often reported out of
identifying regions or subpopulations requiring more access to (vs justification of) epidemiological and clinical context, thus limiting their
antibiotics. ability to inform empirical treatment guidelines
(panel 3).116
This approach could include active sampling of healthy populations across a diversity of The 2014 WHO Antimicrobial Resistance: Global Report on
hosts (ie, human and animal) and environmental sampling. One exemplary and low- Surveillance117 observed that data on antimicrobial resistance
resource approach for community sampling is included in the WHO TriCycle protocol on were scarce for pathogens of major public health
integrated AMR surveillance through analysis of the prevalence of ESBL-producing importance and absent for more than half of the world’s
Escherichia coli in healthy pregnant women.106 Wastewater analysis, currently in countries. The WHO Global Action Plan on Antimicrobial
international validation, can complement human surveillance: resistance rates in isolates Resistance, adopted in 2015,20 emphasised improving the
retrieved from wastewater have been shown to be highly correlated with those of the evidence base of AMR and prompted the 68th World
associated human community.107,108 Health Assembly to recommend NAPs to tackle
Available surveillance information needs to be collated and conveyed to policy makers in resistance.118 The WHO Global Antimicrobial Resistance
easily interpretable forms for decision making. Several COVID-19 platforms that distilled and Use Surveillance System (GLASS) now enables
information about the epidemiological distribution and trajectory of genetic variants harmonised reporting of AMR data by country and sharing
were used by pandemic policy makers.109 Similar tools are emerging for AMR. These tools of aggregated data on AMR prevalence. GLASS has
include pathogen-specific platforms, such as Typhinet and Klebnet, as well as the incorporated data from existing AMR surveillance
ResistanceMap database and amr.watch and amr.net dashboards in development.94 networks, such as the European Antimicrobial Resistance
Data on human exposure to AMR from different domains are one output of the Surveillance Network,119 the Central Asian and European
Integrated One Health surveillance. Other purposes are evaluating trends in AMR or AMU Surveillance of AMR,120 the Latin American Network for
in several domains, monitoring new forms of AMR, and analysing the effectiveness of Antimicrobial Resistance Surveillance (Rede
interventions. These goals require different sample sources, analysis endpoints, and Latinoamericana de Vigilancia de la Resistencia a los
guidance support. Among the efforts to develop guidance on integrated surveillance are Antimicrobianos),121 and the Western Pacific Regional
Joint Actions within the EU and the Quadripartite Technical Group on Integrated Antimicrobial Consumption Surveillance System. After
Surveillance.110 A blueprint for a harmonised sampling effort with ESBL-producing E coli as the 2015–19 early implementation phase, GLASS intro­
one common indicator has been suggested by WHO.111 This integrated TriCycle protocol duced indicators to assess countries’ AMR surveillance,
includes resistance in bloodstream infections and in the community, poultry and poultry including the number of reporting sites, participation in
wet market or slaughterhouse wastewater, human wastewater, and river water.111 First quality-assurance programmes, repre­senta­tiveness of the
TriCycle iterations have been completed in Indonesia,112 Madagascar,113 Ghana,114 and population and health system levels, and laboratory
Pakistan,115 and the protocol is being applied in other countries.115 diagnostics standards. In 2020, GLASS began monitoring
of antimicrobial use and consumption (appendix p 9). In
Modelling to fill data gaps can help synthesise evidence to estimate a burden for addition, WHO has developed survey methods to generate
comparison across regions or diseases and can thus help set priorities. Filling data gaps reliable, representative data on the prevalence and
can also motivate surveillance by presenting people who doubt the model to try to attributable mortality of drug-resistant bloodstream
challenge it with data. Extrapolation has greater uncertainty than gap filling because it infections, particularly where surveillance systems are
assumes that a relationship between AMR and risk factors will remain valid beyond the suboptimum.122,123 These surveys will be initially rolled out
temporal or geographical domains used for training the model. Extrapolations can in Kyrgyzstan, Indonesia, Malawi, and Rwanda, with plans
nevertheless serve a purpose for what-if scenarios. For example, what happens if the for further scaling up in LMICs.
animal sector continues to grow and antibiotics are used with the same intensity as Surveillance has multiple purposes: supporting
currently? It is crucial to differentiate scenarios (ie, what could happen) from projections treatment guidelines, tracking the prevalence of AMR,
(ie, what will happen). identifying practices that exacerbate resistance, evaluating
AMR=antimicrobial resistance. AMU=antimicrobial use. ESBL=extended-spectrum β-lactamase. temporal trends, detecting outbreaks, enabling emergency
preparedness, and informing risk assessment. Surveillance
enables benchmarking of AMR across regions.124–128
For amr.watch see https://amr. cannot be met, nor can progress towards them be Surveillance can follow the evolution of novel resistance
watch/ measured, without robust surveillance of both resistance mechanisms and dangerous resistant clones. For example,
For amr.net see https://amr.net/ and its burden. However, in many parts of the world in 2016 a new family of mobile colistin resistance genes,
surveillance is insufficient for this purpose. Surveillance mcr, were observed following an increase in colistin
strategies might be non-representative of the target resistance identified through routine surveillance.129
population or might bias the responses, including Surveillance data can inform policies for infection
prompting antibiotic overuse.104,105 Traditional laboratory- prevention and control and for antibiotic stewardship.
based resistance surveillance, which aggregates data Once interventions are implemented, surveillance can

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help evaluate their effectiveness prospectively (see the

second paper in this Series21). Surveillance aids in assessing Panel 4: Updating AMR surveillance for the 21st century—
the risk and burden of disease and helps evaluate recommendations
transmission between One Health reservoirs of antibiotic • Every country should have a national surveillance system
resistance, and it can be used to heighten awareness that tracks AMR and antibiotic use, with in-country
among health professionals, policy makers, and the granularity, and that can be used to evaluate programmes
general public. Modalities for surveillance can and should against goals for addressing resistance.
use existing systems and programmes where possible to • Diagnostic testing for patients suspected of having a
provide information at low cost (panel 4). bacterial or fungal infection should be supported at all
Some parts of the world do not undertake enough levels of care, to promote rational antimicrobial use and
susceptibility testing. The Mapping Antimicrobial enhance surveillance.
Resistance and Antimicrobial Use Partnership reports that • Data from routine clinical bacteriology laboratories can
only 1·3% of diagnostic laboratories in sub-Saharan Africa and should contribute to antimicrobial resistance
are capable of bacteriological testing, and only a subset of surveillance system. However, alternative data sources are
those can do susceptibility tests.39 Mycology expertise is also needed to remedy the scarcity of data globally.
truly scarce: fungal surveillance lags bacterial infection Countries should complement routine clinical surveillance
surveillance and is insufficient to support interventions to with other surveillance modules, such as those
tackle the growing prevalence of resistant fungi responsible recommended by WHO. The TriCycle protocol generates
for both community-associated infections and HCAIs. For information on resistance in the clinic, the community,
example, Cryptococcus neoformans, a difficult-to-treat, the food chain, and the environment at low cost.
community-acquired opportunistic infection in people Nationally representative surveys should complement
living with HIV (with a high incidence in Africa) and other laboratory surveillance in settings where coverage of
immunocompromised people, is typically diagnosed late laboratory-based surveillance is poor or quality is
and susceptibility patterns are uncertain. C neoformans unreliable. Surveys will generate reliable, direct
isolates are reported as showing resistance to one or more measurements of AMR prevalence, health, and economic
of the accessible antifungals; backup options are few.131,132 burden to inform national policies and model estimates.
Electronic data capture systems are absent from the • WHO’s methods to estimate attributable mortality of
majority of African hospitals.39 WHONET offers laboratory AMR have been piloted by ACORN104,130 in some LMICs and
data management that is the mainstay of strong can provide data linking AMR with mortality and
surveillance systems in the Philippines and much of morbidity outcomes.
South America; it is compatible with the ACORN • Regulations on antimicrobial distribution must be
platform.133,134 Development of other open-access platforms strengthened to reduce selection for resistance.
tailored to microbiology data, such as SEDRI-LIMS, is Surveillance should be used to inform regulation of
expected to further mobilise laboratory data on antimicrobial distribution, to justify their use of or
antimicrobial susceptibility for surveillance applications. increase access to medicines when most needed.
Data intended to inform empirical prescribing guidelines • Electronic data capture is essential for collating and
must include details of the clinical presentation, sharing surveillance information, as is making this
underlying disease, empirical and subsequent switching information available, in a timely manner and in easily
of therapy, all relevant microbiology results, and in- used formats, to clinical, antimicrobial stewardship, and
hospital and 28-day mortality.102 ACORN enables clinical public health decision makers.
caregivers to collect such information electronically so • The value of existing surveillance systems should be
that it can be merged with laboratory data and shared via evaluated, and the methods honed to increase cost-
easily interpretable dashboard displays.130 effectiveness and the quality and actionability of the
The ultimate value of a surveillance system depends on information obtained.
how the information is used. The use of surveillance data AMR=antimicrobial resistance.
depends on the epidemiological context from which the
data are derived, on the reliability of the data, and the
operational considerations; for example, if surveillance
suggests a change in treatment but the recommended considerable attributable mortality. The burden of
drugs are unavailable, then it has little value. Finally, the resistance is enormous, growing, and unevenly
value of surveillance data depends on estimates of the distributed; it is preventing infectious disease control.
benefit of interventions informed by it—these estimates Everyone is at risk from AMR, including those that have
can then help justify the costs of surveillance. never taken an antibiotic, such as neonates, as they face
the consequences of antimicrobial selective pressure
Conclusion created by previous generations. In parts of Asia and
Antibiotics have saved millions of lives but have also sub-Saharan Africa, the burden is aggravated by the
driven the accompanying resistance pandemic and its scarcity of access to effective antibiotics and infrastructural

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shortfalls that promote the spread of resistant pathogens. 2 Ikuta KS, Swetschinski LR, Aguilar GR, et al. Global mortality
In these cases, AMR is inadequately documented because associated with 33 bacterial pathogens in 2019: a systematic analysis
for the Global Burden of Disease Study 2019. Lancet 2022;
laboratory testing is insufficient and its burden of disease 400: 2221–48.
is poorly measured. Strengthening surveillance is a 3 Gladstone RA, McNally A, Pöntinen AK, et al. Emergence and
prerequisite for halting antimicrobial resistance and dissemination of antimicrobial resistance in Escherichia coli causing
bloodstream infections in Norway in 2002–17: a nationwide,
measuring successes in its containment. longitudinal, microbial population genomic study. Lancet Microbe
Contributors 2021; 2: e331–41.
INO: conceptualisation, project administration, formal analysis, 4 Iroh Tam PY, Musicha P, Kawaza K, et al. Emerging resistance to
methodology, visualisation, original draft writing, and reviewing and empiric antimicrobial regimens for pediatric bloodstream
editing. MEAdK: conceptualisation, original draft writing, and reviewing infections in Malawi (1998–2017). Clin Infect Dis 2019; 69: 61–68.
and editing. TPVB: conceptualisation, data curation, methodology, 5 Carey ME, Dyson ZA, Ingle DJ, et al. Global diversity and
visualisation, original draft writing, and reviewing and editing. CKK: data antimicrobial resistance of typhoid fever pathogens: insights from
curation and visualisation. HS: conceptualisation, original draft writing, a meta-analysis of 13 000 Salmonella Typhi genomes. Elife 2023;
12: e85867.
and reviewing and editing. ACG: conceptualisation, original draft writing,
and reviewing and editing. SB: original draft writing, reviewing, and 6 Langford BJ, So M, Simeonova M, et al. Antimicrobial resistance in
patients with COVID-19: a systematic review and meta-analysis.
editing. MS: original draft writing and reviewing and editing. RL:
Lancet Microbe 2023; 4: e179–91.
conceptualisation, data curation, formal analysis, funding acquisition,
7 Kinross P, Gagliotti C, Merk H, Plachouras D, Monnet DL,
methodology, project administration, resource acquisition, supervision,
Högberg LD. Large increase in bloodstream infections with
visualisation, and reviewing and editing. carbapenem-resistant Acinetobacter species during the first 2 years
Declaration of interests of the COVID-19 pandemic, EU/EEA, 2020 and 2021. Euro Surveill
A meeting held to coordinate this paper was supported by the 2022; 27: 2200845.
Bill & Melinda Gates Foundation (BMGF; INV-055356 to RL) and 8 Cassini A, Högberg LD, Plachouras D, et al. Attributable deaths and
the Africa Centres for Disease Control and Prevention (to all authors). disability-adjusted life-years caused by infections with antibiotic-
resistant bacteria in the EU and the European Economic Area in
Neither funder had any role in the design, writing, or decision to submit
2015: a population-level modelling analysis. Lancet Infect Dis 2019;
this paper for publication. RL has received grant funding from the US
19: 56–66.
National Science Foundation (CCF1918628). INO is a Calestous Juma
9 Liu L, Oza S, Hogan D, et al. Global, regional, and national causes
Science Leadership fellow supported by BMGF (INV-036234, as well as
of child mortality in 2000–13, with projections to inform post-2015
INV-067684, INV-048135, and OPP1210746); receives grant funding from priorities: an updated systematic analysis. Lancet 2015; 385: 430–40.
the UK National Institute for Health and Care Research (project number 14 Mahtab S, Madhi SA, Baillie VL, et al. Causes of death identified in
NIHR133307), Wellcome Trust, Public Health Alliance for Genomic neonates enrolled through Child Health and Mortality Prevention
Epidemiology, SEQAFRICA, Grand Challenges Africa Award Surveillance (CHAMPS), December 2016–December 2021.
(GCA/DD/rnd3/021), and International Vaccine Institute Award; receives PLOS Glob Public Health 2023; 3: e0001612.
royalties from Oxford University Press, Cornell University Press, and 10 Chaurasia S, Jeeva Sankar M, Agarwal R, et al. Characterisation and
Springer; receives consulting fees from the Wellcome Trust; has received antimicrobial resistance of sepsis pathogens in neonates born in
payment for lectures from the UK Microbiology Society; received travel tertiary care centres in Delhi, India: a cohort study. Lancet Glob Health
support from BMGF, the European Society for Clinical Microbiology and 2016; 4: e752–60.
Infectious Disease, and the American Society for Microbiology; has or had 11 Sands K, Carvalho MJ, Portal E, et al. Characterization of
paid leadership roles in BMGF’s surveillance advisory group (2019–21), antimicrobial-resistant Gram-negative bacteria that cause neonatal
the Thomas Bassir Biomedical Foundation Nigeria (2019 to present), and sepsis in seven low- and middle-income countries. Nat Microbiol
The International Centre for Antimicrobial Resistance Solutions Technical 2021; 6: 512–23.
Advisory Forum (2021 to present); and has other unpaid positions in the 12 Ingle DJ, Levine MM, Kotloff KL, Holt KE, Robins-Browne RM.
African Journal of Laboratory Medicine, Microbial Genomics, Dynamics of antimicrobial resistance in intestinal Escherichia coli
The Lancet Infectious Diseases, Nigeria Center for Disease Control, and from children in community settings in south Asia and sub-
Saharan Africa. Nat Microbiol 2018; 3: 1063–73.
the Lancet Commission for Nigeria. SB is a member of staff at WHO; the
views presented in this Series paper are those of the authors and do not 13 Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant
pathogens associated with healthcare-associated infections:
reflect those of WHO. ACG receives consulting fees from Aché,
summary of data reported to the National Healthcare Safety
Eurofarma, and União Química; receives payment for lectures from
Network at the Centers for Disease Control and Prevention,
bioMérieux, Eurofarma, MSD, Pfizer, and Sandoz; received travel support 2009–2010. Infect Control Hosp Epidemiol 2013; 34: 1–14.
from MSD and Pfizer; participates on the data monitoring board of Aché,
15 Murray CJ, Aravkin AY, Zheng P, et al. Global burden of 87 risk factors
Eurofarma, Hypera Pharma, MSD, Pfizer, Roche, Sandoz, United Medical, in 204 countries and territories, 1990-2019: a systematic analysis for
União, and Química; is a member of the Scientific Advisory Committee of the Global Burden of Disease Study 2019. Lancet 2020; 396: 1223–49.
the Global Antibiotic Research and Development Partnership (GARDP), 16 Statista Research Department. Proportion of selected age groups of
the Health 1 Area Coordination board, and Fundação de Amparo à world population and in regions in 2022. 2023. https://www.
Pesquisa do Estado de São Paulo; and is a researcher for the Brazilian statista.com/statistics/265759/world-population-by-age-and-
National Council for Scientific and Technological Development. MS region/#:~:text=Globally%2C%20about%2025%20percent%20
receives funding from the Wellcome Trust (222051/Z/20/Z), GARDP, and of,over%2065%20years%20of %20age (accessed March 19, 2024).
EDCTP (NeoSep1); has unpaid leadership positions on the WHO Essential 17 Teillant A, Gandra S, Barter D, Morgan DJ, Laxminarayan R.
Medicine List Antibiotics Working Group and GARDP; and has been the Potential burden of antibiotic resistance on surgery and cancer
Chief Investigator of clinical trials in children, where generic antibiotics chemotherapy antibiotic prophylaxis in the USA: a literature review
have been donated by Sandoz, InfectoPharm, and Shionogi. All other and modelling study. Lancet Infect Dis 2015; 15: 1429–37.
authors report no competing interests. 18 Ikhimiukor OO, Odih EE, Donado-Godoy P, Okeke IN. A bottom-
up view of antimicrobial resistance transmission in developing
Acknowledgments countries. Nat Microbiol 2022; 7: 757–65.
We thank John Stelling and Christiane Dolecek for helpful comments 19 Bouiller K, Bertrand X, Hocquet D, Chirouze C. Human infection
and are grateful to Ambika Lall, Isabella Impalli, and Sally Atwater for of methicillin-susceptible Staphylococcus aureus CC398: a review.
figure and editorial assistance. Microorganisms 2020; 8: 1737.
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