by Tamar Kahn


Multidrug-resistant bacteria on the increase

No new antibiotics in the pipeline
Bacteria becomes drug resistant

YOLANDA contracted her first urinary tract infection when she was 17. When she was 20 the painful attacks were an almost fortnightly occurrence, and she was on a first-name basis with staff at a pathology laboratory.

The infections strained her relationship, made her anxious about travelling and took a toll on her mental health. She was uneasy about taking repeated courses of antibiotics and tried alternative remedies ranging from acupuncture to cranberries, but none worked.

The antibiotics she was prescribed would take effect within hours and she’d do her best to put the miserable experience behind her.

That changed in November 2012 when she was admitted to hospital with a kidney infection caused by a strain of bacteria resistant to almost all antibiotics. The cause was identified as an Extended Spectrum Beta Lactamase-producing strain of E. coli which makes enzymes that destroy a range of antibiotics such as penicillins and cephalosporins.

The multiple courses of antibiotics she had taken had probably allowed drug-resistant strains of the bacterium to flourish in her body.

"It was a very scary infection. I remember a nurse saying I only had a few drugs left," says Yolanda, who asks not to be identified to protect her privacy, as her cystitis attacks are triggered by sexual intercourse.

She winces at the memory of the ice-cold intravenous ertapenem that cured her infection.

Cases such as Yolanda’s have grown over recent years, raising fears that the "golden era" of antibiotic discovery is rapidly drawing to a close.

A suite of drugs was developed after Alexander Fleming’s discovery of penicillin in 1928, turning once terrifying infectious diseases into relatively benign ailments, and it appeared that science was winning the war against infectious diseases. But since the 1980s the development of new antibiotics has dwindled as pharmaceutical companies set their sights on more lucrative targets such as cancer.

Drug development is an expensive, high-risk pursuit. Sanofi, Eli Lilly and Bristol-Myers Squibb halted research on new antibiotics in the 1990s and in 2011 Pfizer shut its US antibiotic research facility. The rate at which the US Food and Drug Administration approves new antibiotics plummeted from 17 between 1980 and 1984 to just two between 2010 and 2012.

Only two new classes of antibiotics have been discovered since the 1970s and experts such as Ampath Laboratories microbiologist Adrian Brink worry that there won’t be more for at least a decade.

Doctors warn that unless the antibiotics available are used wisely, for the next generation something as trivial as an infected scratch could be lethal and many routine surgical procedures will become extremely risky — if not impossible.

The science behind antibiotic resistance is fairly well understood: as the targeted bacteria replicate, some evolve with genes that protect them from the antibiotic. With each successive generation, the proportion of bacteria with drug-resistant genes increases until the drug is no longer effective. Inappropriate use of antibiotics in animals and humans speeds this process up dramatically.

Multidrug-resistant bacteria are now frequently found in hospitals and increasingly among communities.

"These bugs are literally ticking time bombs," says Fathima Paruk, director of the cardiothoracic intensive care unit at the University of the Witwatersrand. "They are easily transferred to anyone from an infected patient by simple body contact. They can be transferred to surfaces like stethoscopes and bed linen and spread easily if simple infection control rules, such as hand washing, are not heeded."

At least 25,000 patients in Europe and 23,000 in the US die from antibiotic-resistant infections each year, according to the World Alliance Against Antibiotic Resistance.

"We must change how antibiotics are used and adopt proactive strategies, similar to those used to save endangered species," alliance president Jean Carlet said in a June declaration that described antibiotic resistance as one of the biggest public health threats of our time.

A report released earlier this year by the World Health Organisation highlighted the problems of drug-resistant tuberculosis and HIV. It also drew attention to the rise of treatment-resistant bacteria such as Klebsiella pneumonia, which causes common infections such as urinary tract or blood infections, and the detection of treatment-resistant gonorrhoea in 10 countries, including SA.

Antibiotic-resistant infections are not notifiable diseases, so doctors don’t have to report them to authorities. As a result, the Department of Health doesn’t have a national surveillance system or locally representative data for antibiotic resistance. 

What few data there are tell an alarming story, says the department’s head of sector-wide procurement, Gavin Steel. In the first six months of 2011, the Medicines Control Council received 214 applications to import a last-resort antibiotic called colistin, which is not registered in SA. The number of applications soared to 657 in the first half of this year.

"Its usage gives us a window into how many infections could not be managed with antibiotics available in SA. It is not suitable for all infections, and many patients may not present to a site where it is available, so it is merely an indicator," says Mr Steel.

A study on antibiotic resistance at the Red Cross Children’s Hospital between 2007 and 2011 found 72% of patients had acquired Staphylococcus aureus infections — which can cause pneumonia, bone or skin infections — and had bugs that were methicillin-resistant.

Judicious use of antibiotics requires doctors to make an appropriate drug selection by testing the bacteria in question for antibiotic susceptibility, and then prescribing the correct dose for the appropriate duration. But all too often, doctors fail to order these tests and prescribe broad-spectrum drugs in the hoping of killing the target bacteria.

"People need to understand that antibiotics are incredibly useful drugs when you need them. But when you don’t, you are potentially selecting out resistant bugs that will colonise your body which you can spread around to other people," says Prof Mendelson.

"There is massive overprescription for nonbacterial infections, like colds and flu. You’d be amazed at what people get antibiotics for. A study in KwaZulu-Natal in 2003 found two-thirds of patients expected an antibiotic: doctors thought antibiotics were indicated in 70% of their cases but provided them in 80%.

"There is also sloppy prescribing in hospitals, with poor knowledge of which drugs to use, at what dosage and for how long. We have a lot of work to do."

A study published in the South African Medical Journal in 2012 found antibiotic use in public sector intensive-care units in 2005 was better than in the private sector, partly because government facilities exerted tighter control over antibiotic use.

The situation in the private sector has improved somewhat since then, says Discovery Health consultant Gary Kantor, citing a Discovery initiative that monitors antibiotic use in private hospitals and relays information to the facilities to encourage better use of this dwindling resource.


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