Prof Keertan Dheda

The recently established Centre for the Study of
Antimicrobial Resistance (CAMRA) at UCT is an extraordinary development in the
internationally urgent study of antimicrobial resistance among
multidrug-resistant pathogens. The unit is funded by the South African Medical
Research Council (SAMRC) and directed by UCT Professor of Respiratory Medicine,
Prof Keertan Dheda

Not only will the work of the SAMRC Extra Mural Unit fortify
the World Health Organisation’s (WHO) critical call for attention to the crisis
of drug resistance – which has been prioritised alongside global warming – but
it is also the first South African unit dedicated to
studying the origin, development and fundamental drivers of antimicrobial
resistance and multidrug-resistant pathogens.

“If the issues of antimicrobial resistance and
multidrug-resistant pathogens are not addressed, we will head into a
post-antibiotic era analogous to the 18th and 19th centuries. Common infections
and minor injuries will once again kill people on a large scale,” says Dheda,
who was last year awarded an A-rating by the National Research Foundation for
his contributions to the field of pulmonology, with a specific focus on
tuberculosis (TB). “This is already starting to happen.”

“Substantial morbidity and mortality due to
multidrug-resistant infections, major health cost implications, and wider
impact on society and the economy will not only retard economic growth, but
there are also serious risks that it will undo the gains made under the United
Nations’ Millennium Development Goals.”

The new centre will combine the efforts of several
multi-disciplinary national and international authorities in the fields of TB
and antimicrobial resistance to study the movement and distribution of drugs in
the body, molecular sequencing and the development of inhaled drugs. The unit
includes members and collaborators from the University of KwaZulu-Natal,
University of Pretoria, Stellenbosch University, Walter Sisulu University,
Sefako Makgatho Health Sciences University, SA National Institute of
Communicable Diseases, London School of Hygiene and Tropical Medicine,
University of Parma (Italy), and the Baylor Scott & White Research
Institute in Dallas, Texas, in addition to those from UCT.

Given the high rate of drug-resistant TB in South Africa and
because TB is a poverty- and HIV-related disease, Dheda says the unit will
place special emphasis on this area of antimicrobial resistance. TB is now the
foremost infectious disease killer worldwide and the commonest cause of death
in South Africa. Almost 25% of TB strains globally are resistant to at least
one major TB drug and drug resistant-TB contributes heavily to TB mortality.

“TB drug resistance and resistance to antibiotics threatens
the gains we have made in health in South Africa,” says SAMRC President, Prof
Glenda Gray. “Bold efforts are required to tackle drug resistance at a global
level and the SAMRC is committed to funding research that will endeavour to
find solutions that make global impact.”

Preventative strategies, antibiotics, vaccination, economic
and psychosocial issues, and promotion of the appropriate use of antibiotics –
also known as antibiotic stewardship – are among the many aspects of
antimicrobial resistance that demand attention.

“A further worrying phenomenon is that there are hardly any
new antibiotics entering the commercial pipeline,” says Dheda. “It is thus
critical that newer and novel antibiotic classes be protected at all costs.

“However, this will not happen unless we understand the key
drivers and pathogenesis of antibiotic resistance.”

We know that exposing bacteria to levels of antibiotic below
what’s required to be effective is a key driver of antibiotic resistance. What
is not known, however, is to what extent this occurs in specific clinical
contexts, how resistance evolves and how it will be possible to prevent or at
least minimise the development and evolution of resistance using better
strategies for dosage and administration.

“CAMRA will address these key gaps in our knowledge,” says
Dheda. “Moreover, we take a strategic view that inhaled antibiotics that
supplement the primary treatment regimen will play an important role in
antibiotic stewardship and effective treatment for multidrug-resistant
pathogens. Thus, one of the long-term aims of the proposal is to establish a
multi-disciplinary platform for the future study of inhaled antibiotics.

“This will address a further gap in current capacity and
infrastructure as no such facility exists within South Africa.”

The unit’s initial objectives, says Dheda, can be categorised
under three broad descriptions. CAMRA will:

  • Interrogate the relationship between drug concentrations and
    efficacy at the site of disease, including the lung;
  • Develop new methods to improve diagnostic sensitivity for
    the detection of rare populations of more resistant microbes undetectable by
    conventional methods in sputum and blood, and compare these to the site of
    disease; and
  • Conduct preliminary studies to determine the levels and
    efficacy of additional inhaled antibiotics at the site of disease both for TB
    and multidrug-resistant bacterial pneumonia. Thus, CAMRA will study both TB and
    non-TB bacterial pathogens.

“There are also important capacity development aspects of
the project, including uplifting nascent academic centres, and championing
transformation and gender equality,” explains Dheda.  

The project is expected to span 10 to 15 years with the
SAMRC funding addressing aspects of the team’s initial aims and helping to
generate preliminary data to leverage further funding.