antibiotics

The World Health Organization has been urged to update its guidelines on the use of antibiotics in developing countries after a study found that thousands of infants were dying from infections that could be prevented.

The study, which stretched over 11 countries and involved over 3,200 babies, is one of the largest of its kind ever conducted and suggests that western policy guidelines around the use of antibiotics may be causing more harm than good in Africa and other developing areas.

“WHO guidelines are absolutely outdated,” said Professor Angela Dramowski, a paediatric infectious diseases specialist at Stellenbosch University in Cape Town and one of the paper’s lead authors.

“Until now guidelines were generated from high income country settings, and try to apply it to the African context. And there’s clearly a mismatch.”

The study, conducted by the Global Antibiotic Research and Development Partnership, focused on rates of sepsis – the body’s extreme response to an infection – in neonatal babies.

It found “extensive variation in mortality” between the 19 hospitals in the study, ranging from 1.6 per cent to 27.3 per cent, “with markedly higher rates” in low and middle income countries (LMICs).

Preterm babies ‘extremely vulnerable’ to infection

Experts said there were three reasons for the poor performance of poorer countries: clinicians were holding back antibiotics for fear of feeding antibiotic resistance; infections in infants that can cause sepsis are more common in poor countries and require different  antibiotics earlier; and antibiotic resistance itself is becoming more widespread

In terms of the WHO’s recommendations for sepsis treatment, the second point was most important, said Prof Dramowski. “The profile of pathogens and AMR rates in LMIC make the recommended antibiotics less likely to be effective in LMIC neonatal units,” she said.

Seamus O’Brien, Research & Development Director at the Global Antibiotic Research & Development Partnership, said the study’s findings came as a surprise.

Globally there are 600,000 deaths from sepsis per year, with 200,000 resulting from AMR, according to Prof Dramowski.

A total of 95 per cent of these deaths are in lower and middle income countries.

But Prof Dramowski said that experts believe that the global number of babies dying from infections is grossly underestimated.

Preterm babies are extremely vulnerable to infection because they have underdeveloped immunity.

“They have very fragile barriers, all the things that protect us from infection like intact skin, intact gastrointestinal tract, in them are also underdeveloped. And they remain hospitalised for extended periods,” said Prof Dramowski.

The research showed that many physicians were forced to use antibiotics such as carbapenems, which are typically reserved for treating severe bacterial infections, due to the high degree of antibiotic resistance to the recommended treatments in their units.

These drugs are classified by the WHO as “Watch” antibiotics, meaning they are recommended only for specific, limited purposes as they need to be preserved.

These antibiotics function as “back up” treatments as antibiotic resistance against other treatments increases.

They were often the only antibiotics available to treat the infection, forcing clinicians to move beyond WHO recommendations.

The research also found wide variation in treatment. More than 200 different antibiotic combinations were used by hospitals reviewed in the study, with frequent switching of antibiotics due to high resistance to treatments.

Prof Dramowski explained that WHO recommendations are “several decades old now” and are based on data from before 2000 and high-income countries, which have a different AMR profile.

Last-line antibiotics, used to treat infections with bacteria that are resistant against common antibiotics, or, in cases of severe infections, were prescribed to 15 per cent of babies with sepsis enrolled in the study.

Experts worry that using these antibiotics could worsen the risk posed by AMR.

“There’s a fine line that we walk as clinicians to try to give our best antibiotics first and, at the same time, also not to overuse those antibiotics of last resort,” said Prof Dramowski.

She fears that without rapid action to increase infection control and treatment options, there could be a reversal in survival rates in newborn babies in the next ten and twenty years, dirven by neonatal sepsis and antibiotic resistance.

“We need more resources that are focused on the area of newborn survival, and particularly infection in low middle income countries, because really, that’s the elephant in the room.”