Comment
Commission, Department of Laboratory Medicine, The First 6 Hong H, Xu J, McGoogan J, Dong H, Xu G , Wu X. Relationship between the
Affiliated Hospital, China Medical University, Shenyang, China
(JX); Department of AIDS/STD Control and Prevention, Tianjin
Center for Disease Control and Prevention, Tianjin, China (MY);
Department of STD Control and Prevention, Nanshan District
Center for Chronic Disease Control, Shenzhen, China (ZL);
Guangzhou Eighth People’s Hospital, Guangzhou, China (WC)
zouhuachun@mail.sysu.edu.cn
We declare no competing interests.
1 Sohu News. Voice from the National People’s Congress and the Chinese
People’s Political Consultative Conference 2017. 2017. http://www.sohu.
com/a/128715460_464387 (accessed Nov 29, 2017; in Chinese).
2 Zhang P, Chi X, Wu M, Wang S, Wang J. Status and influencing factors of
attitude toward LGBT among college students.
Chinese Journal of Public Health 2012; 28: 921–23 (in Chinese).
3 Ministry of Education. Ministry of Education issues latest university list.
2017. http://www.moe.edu.cn/jyb_xwfb/s5147/201706/
t20170616_307075.html (accessed Aug 21, 2017; in Chinese).
4 Chang J, Lu W. HIV-related knowledge, attitude and behavior among
university MSM in Guiyang. Chinese Journal of School Health 2014;
35: 500–02 (in Chinese).
5 Huang Y, Ma Y, Hu Y, et al. Characteristics of the age at first intercourse and
associated risk factors among college students in 15 provinces of China.
Capital Journal of Public Health 2017; 11: 99–102 (in Chinese).
Classifying antibiotics in the WHO Essential Medicines List
for optimal use—be AWaRe
Optimising the use of antimicrobials is a key priority of
the global strategy to combat antimicrobial resistance.1
Antibiotic usage guidance should be developed to meet
the aims of Sustainable Development Goal 3: achieving
universal access to safe, effective, quality, and affordable
medicines.2 Improving global prescribing is a complex
issue that requires pragmatic short-term targets,
ambitious long-term goals, and realistic expectations.
In low-income and middle-income countries, it is
difficult to identify specific targets for intervention.3
Furthermore, sustained, reliable availability of antibiotics
at an affordable cost and adequate quality remains a
major concern for high-income, low-income, and middle-
income countries.4 Regular shortages and the high cost
of older, off-patent antibiotics are an increasing threat to
their optimal use.5 Defining which antibiotics should be
the focus at different levels of stewardship intervention is
a global priority.6
Revision of the Essential Medicines List (EML) entails
complex decisions that assess health outcomes while
accounting for feasibility, monitoring, registration, and
cost of listed medications.7 The last complete revision of
antibiotics was done in 2001.8 For the 2017 update on the
18
use of gay mobile phone applications and HIV infection among men who
have sex with men in Ningbo, China: a cross-sectional study. Int J STD AIDS
2017; published online Nov 3. DOI:10.1177/0956462417738468.
7 Duan C, Wei L, Cai Y, et al. Recreational drug use and risk of HIV infection
among men who have sex with men: A cross-sectional study in Shenzhen,
China. Drug Alcohol Depend 2017; 181: 30–36.
8 Burki T. Sex education in China leaves young vulnerable to infection.
Lancet Infect Dis 2016; 16: 26.
9 Ministry of Education. University HIV reporting mechanism will be
established in China. 2015. http://www.moe.gov.cn/jyb_xwfb/
s5147/201508/t20150811_199281.html (accessed Aug 24, 2017;
in Chinese).
10 Chinese National Center for AIDS/STD Control and Prevention.
HIV prevention programs in universities 2016. 2016. http://ncaids.
chinacdc.cn/fzdt/zxdt/201704/t20170424_142296.htm (accessed
Aug 21, 2017; in Chinese).
11 Zou H, Fan S. Characteristics of men who have sex with men who use
smartphone geosocial networking applications and implications for HIV
interventions: a systematic review and meta-analysis. Arch Sex Behav 2017;
46: 885–94.
12 Tang W, Han L, Best J, et al. Crowdsourcing HIV test promotion videos:
a noninferiority randomized controlled trial in China. Clin Infect Dis 2016;
62: 1436–42.
EML, comprehensive reviews on antibiotic use for specific
clinical infections were commissioned by WHO.9 After
assessing the evidence on the most frequent and severe
bacterial infections, the Expert Committee identified a
few options as first-choice and second-choice antibiotics
for each type of infection and categorised antibiotics
into three groups, with the goals of improved access and
clinical outcomes, reduced potential for development of
antimicrobial resistance, and preserved effectiveness of
the so-called last-resort antibiotics (figure).
To improve access to effective therapy, the Committee
first designated specific Access antibiotics. Antibiotics
selected for the Access group were those listed as first and
second choices for the empirical treatment of 21 common
or severe clinical syndromes. First choices were generally
narrow spectrum agents with a low toxicity risk. Second
choices for specific syndromes were broader spectrum
antibiotics than the first choices, which might have
an increased risk of toxicity or resistance selection.
This Access designation for 29 antibiotics emphasises
their role as the core set of antibiotics that should be
consistently available everywhere at an appropriate
quality, dose, duration, formulation, and price.
www.thelancet.com/infection Vol 18 January 2018
 Comment

The Watch group includes antibiotic classes that

were considered to have higher toxicity concerns Access
Amoxicillin Azithromycin
or resistance potential compared with the Access Amoxicillin and clavulanic acid Cefixime
Ampicillin Cefotaxime
group. This group also substantially overlaps with Benzathine benzylpenicillin Ceftriaxone
Benzylpenicillin Ciprofloxacin
the highest priority agents on the list of critically Cefalexin or cefazolin Clarithromycin
important antimicrobial drugs for human medicine,10 Chloramphenicol Piperacillin and tazobactam
Clindamycin Meropenem
which indicates the antibiotics that should not be used Cloxacillin Vancomycin
Doxycyline
for prophylactic uses in food producing animals and Gentamicin or amikacin * Antibiotics that are
agriculture. A small number of antibiotics from the Metronidazole also in the Watch group
Nitrofurantoin
Watch group were also recommended as first or second Phenoxymethylpenicillin
Procaine benzylpenicillin
choice treatments for a few, specific indications. Spectinomycin
Antibiotics were designated to the Watch group to Sulfamethoxazole and trimethoprim

assist the development of tools for stewardship at Core access antibiotics

local, national, and global levels. Active monitoring of
the Watch antibiotics is encouraged through point-
prevalence surveys to ensure that use aligns with
guidance.
The Reserve group includes antibiotics that should
be treated as last-resort options. These should be
accessible when needed, but use should be tailored
to very specific patients and clinical settings when
other alternatives have failed or cannot be used (eg,
serious or life-threatening infections due to multidrug-
resistant bacteria). To preserve their effectiveness, these
medicines should be protected and prioritised as key
targets of high-intensity national and international
stewardship programmes that involve central
Watch
Anti-pseudomonal penicillins with beta-lactamase inhibitor
(eg, piperacillin and tazobactam)
Carbapenems or penems (eg, faropenem, imipenem and cilastatin,
meropenem)
Cephalosporins, third generation (with or without beta-lactamase inhibitor;
eg, cefixime, cefotaxime, ceftazidime, ceftriaxone)
Glycopeptides (eg, teicoplanin, vancomycin)
Macrolides (eg, azithromycin, clarithromycin, erythromycin)
Quinolones and fluoroquinolones (eg, ciprofloxacin, levofloxacin,
moxifloxacin, norfloxacin)
Reserve
Aztreonam
Cephalosporins, fourth generation (eg, cefepime)
Cephalosporins, fifth generation (eg, ceftaroline)
Daptomycin
Fosfomycin (intravenous)
Oxazolidinones (eg, linezolid)
Polymyxins (eg, colistin, polymyxin B)
Tigecycline

monitoring and reporting. The Reserve group also

includes newer antibiotics.
Several major limitations to this new broad
categorisation remain. Not all classes of antibiotics
are included in the list. There is a weak evidence base
to indicate that specific antibiotics or classes should
go into the different categories; however, to facilitate
stewardship, the association between use of specific
classes and propensity for resistance selection seemed
sufficient to recommend this categorisation. It is
recognised that the EML will need local adaptation and
further revision over time.
A standing EML Working Group has been established
to review additional syndromes, adapt new synopses
that arise into short, structured documents, coordinate
the development of a guidance document on optimal
dose and duration of antibiotic treatments, and to
improve methods for communicating the stewardship
messages associated with these new Access, Watch, and
Reserve (AWaRe) groups.
Figure: List of antibiotics, classified into Access, Watch, and Reserve groups,
to improve prescribing decisions
An AWaRe index, a novel metric for stewardship,
could be introduced to help estimate the relative use
of narrow-spectrum and broad-spectrum antibiotics.
This index could enable relevant stakeholders to track
progress in optimising use of medicines, evaluate the
effects of interventions, and define goals for quality
improvement. WHO member states would need to be
supported as the clinical guidance is contextualised and
implemented in their health-care settings.
Mike Sharland, Celine Pulcini, Stephan Harbarth, Mei Zeng,
Sumanth Gandra, Shrey Mathur, *Nicola Magrini, on behalf
of the 21st WHO Expert Committee on Selection and Use of
Essential Medicines
Paediatric Infectious Diseases Research Group, Institute for
Infection and Immunity, St George’s, University of London,
London, UK (MS, SM); Department of Infectious Diseases, Centre

www.thelancet.com/infection Vol 18 January 2018 19

 Comment
For examples of Kouzou Sakai’s
work see http://www.folioart.
co.uk/illustration/folio/artists/
illustrator/kouzou-sakai
20
Hospitalier Régional Universitaire (CHRU) de Nancy, Nancy, France
(CP); and EA 4360 APEMAC, University of Lorraine, Nancy, France
(CP); Infection Control Programme, University of Geneva
Hospitals, Geneva, Switzerland (SH); Department of Internal
Medicine, Faculty of Medicine, University of Geneva, Geneva,
Switzerland (SH); Department of Infectious Diseases, Children’s
Hospital of Fudan University, Shanghai, China (MZ); Centre for
Disease Dynamics, Economics & Policy, New Delhi, India (SG); and
Department of Essential Medicines and Health Products, World
Health Organization, 1211 Geneva 27, Switzerland (NM)
magrinin@who.int
MS reports grants from GlaxoSmithKline, Pfizer, Cubist Pharmaceuticals, and the
Drugs for Neglected Diseases Initiative outside the submitted work. CP reports a
grant from the Innovative Medicines Initiative and personal fees from Pfizer
outside the submitted work. SH reports grants from the Innovative Medicines
Initiative, Pfizer, and BioMérieux outside the submitted work; and reports
personal fees from Novartis, GlaxoSmithKline, Debiopharm, and Janssen outside
the submitted work. All other authors declare no competing interests.
1 WHO. Global action plan on antimicrobial resistance. 2015. http://apps.
who.int/iris/bitstream/10665/193736/1/9789241509763_eng.pdf
(accessed Dec 5, 2017).
2 United Nations. Transforming our world: the 2030 Agenda for Sustainable
Development. 2015. https://sustainabledevelopment.un.org/content/
documents/21252030%20Agenda%20for%20Sustainable%20
Development%20web.pdf (accessed Dec 5, 2017).
The cover artist for this year
The 2018 cover artist for The Lancet Infectious Diseases
is Kouzou Sakai, who replaces Andrew Lyons. We
thank Andrew for his colourful and striking covers that
have helped The Lancet Infectious Diseases to be easily
recognisable among the medical journals throughout
2017. Personally, it has been a great pleasure working with
Andrew, and the arrival of the sketches for the new cover
was always an eagerly awaited moment each month.
Kouzou is a Japanese artist based in Tokyo and is
affiliated to the Folio Illustration Agency. Having
graduated from the Department of Animal Science and
Biotechnology, Kouzou has a special affinity towards
3 Wirtz VJ, Hogerzeil HV, Gray AL, et al. Essential medicines for universal
health coverage. Lancet 2017; 389: 403–76.
4 Pulcini C, Beovic B, Béraud G, et al. Ensuring universal access to old
antibiotics: a critical but neglected priority. Clin Microbiol Infect 2017;
23: 590–92.
5 Pulcini C, Mohrs S, Beovic B, et al. Forgotten antibiotics: a follow-up
inventory study in Europe, the USA, Canada and Australia.
Int J Antimicrob Agents 2017; 49: 98–101.
6 Davey P, Marwick CA, Scott CL, et al. Interventions to improve antibiotic
prescribing practices for hospital inpatients. Cochrane Database Syst Rev
2017; 2: CD003543.
7 Magrini N, Robertson J, Forte G, et al. Tough decisions on essential
medicines in 2015. Bull World Health Organ 2015; 93: 283–84.
8 WHO. WHO global strategy for containment of antimicrobial resistance.
2001. http://www.who.int/drugresistance/WHO_Global_Strategy_English.
pdf (accessed Dec 5, 2017).
9 WHO. Executive summary: the selection and use of essential medicines.
Report of the 21st WHO Expert Committee on the Selection and Use of
Essential Medicines. 2017. http://www.who.int/medicines/publications/
essentialmedicines/EML_2017_ExecutiveSummary.pdf (accessed
Dec 5, 2017).
10 WHO Advisory Group on Integrated Surveillance of Antimicrobial
Resistance (AGISAR). Critically important antimicrobials for human
medicine. 5th revision 2016. June 2017. http://www.who.int/foodsafety/
publications/antimicrobials-fifth/en/ (accessed Dec 5, 2017).
all kinds of animals, especially cats, so we hope that
he will include some in our future covers. Kouzou did
illustrations for Haruki Murakami’s novel “Colorless
Tsukuru Tazaki and His Years of Pilgrimage” and cites
René Magritte as an inspiration. His style combines
nature and surreal and mysterious worlds with bright
informative graphics. It is very exciting to have Kouzou
as our cover artist this year, and we look forward to
working with him for the coming 12 months.
Marco De Ambrogi
The Lancet Infectious Diseases
www.thelancet.com/infection Vol 18 January 2018