Antibiotic shortage puts patients at risk, doctors fear

Exclusive: supply problems with one of most widely used drugs mean doctors are being forced to ration its use and switch to less desirable alternatives

 Hospitals warn over stocks of drug used to treat cystic fibrosis, pneumonia, urinary tract infections. Photograph: David Goldman/AP

Nicola Davis-Saturday 1 July 2017 

A major shortage of one of the most widely used hospital antibiotics is putting patients at risk, doctors have warned.

There is an international shortage of of piperacillin-tazobactam, an antibiotic and antibacterial combination drug known by the trade name Tazocin, which is usually used intravenously in intensive care. It is also used to treat a wide variety of conditions including cystic fibrosis, pneumonia, urinary tract infections, diabetic foot infections and neutropenic sepsis – a life-threatening condition that can arise in those receiving anti-cancer treatment.

The Department of Health and Public Health England have issued guidance on the problem and hospitals in Scotland have been given advice by the Scottish Antimicrobial Prescribing Group (SAPG). A document from NHS Fife dating from early May says “there is a high likelihood that in the near future piperacillin-tazobactam will not be available at all… this is a major challenge to our prescribing practice.”

The document also points out that the use of other drug combinations could increase the workload for doctors and nurses, as some of them require more frequent doses and increased monitoring. “Regrettably there is no other feasible solution at present,” it notes.

Philip Howard, Royal Pharmaceutical Society spokesman on antimicrobial resistance, said that an explosion at a Chinese factory that produced raw materials for the medication had caused the problems. Howard said the UK had experienced supply constraints since March this year.

Hospitals in the UK have been urged to restrict their use of the drug in order to conserve stocks. “This is one of the more serious shortages that the NHS has had to face,” Howard said, although he added there were enough supplies of other drugs for patients to get the antibiotics they needed.

Documents approved by the Department of Health and Public Health England dated 24 April, seen by the Observer, advise that the use of piperacillin-tazobactam be restricted to severe cases of sepsis and ventilator-acquired pneumonia, although some doctors fear that if the shortage lasts then these patients could also be affected. Doctors wanting to use the medication for other cases must get approval.

A doctor who works at a hospital in East Anglia, who asked to remain anonymous, said he was advised of the piperacillin-tazobactam shortage by the pharmacy team at his NHS trust on 18 May in an email stating “we will not be able to obtain any further stock in the foreseeable future once we have used up all our current stock”.

The doctor said he believed patients were being put at risk by the shortage. “Every hospital in this country would use it,” he said. “[If you look] at the grades of antibiotics we have, [piperacillin-tazobactam] is probably the second rung from the top. It is not quite the last resort, but it is almost.”

He said many of the options doctors were having to use were less powerful or could cause side effects such as kidney damage. “Patients are either having prolonged stays on these courses of antibiotics, or even worse, they are not actually even responding,” he added.

In such cases, he said, doctors were increasingly left having to deploy the last line of defence – an antibiotic known as meropenem, part of a group of antibiotics known as carbapenems. But resistance to such drugs is a growing problem, and doctors are already advised to limit their use. A microbiologist at a hospital in England, speaking on condition of anonymity, said meropenem was being used more often than he would like, while critical shortages had also been encountered for other drugs.

In the case of one antibiotic called ceftriaxone, which is used as the first line of treatment for meningitis, the Observer has seen a memo from his NHS trust to staff which said it expected to exhaust all its supplies of the drug within the next few days.

The microbiologist added that the use of antibiotics known as cephalosporins, which includes ceftriaxone, had previously been reduced in the UK to help reduce the threat of the dangerous superbug C difficile. Any rise in use of the drugs, he said, could increase the risk of such infections.

The cost of piperacillin-tazobactam and other drugs had shot up, the microbiologist added, while the workload for microbiologists had also increased, due to the number of calls from doctors and emergency meetings to discuss shortages.

In another document seen by the Observer, the Department of Health acknowledged that the shortage of piperacillin-tazobactam could cause problems with supplies of other drugs – a situation Howard also admitted was possible. He added that recent data did not show a significant rise in the use of meropenem.

The Department of Health said the piperacillin-tazobactam shortage was a global issue and that more supplies should be available this summer. “In the interim period we are working with the pharmaceutical industry and NHS to make sure supplies of alternative antibiotics are available and have issued guidance about appropriate alternative treatment options,” it said.

Andrew Seaton, chair of the SAPG, said they did not advise health boards to increase the use of cephalosporins, except in certain cases, due to concerns over a possible increase in C difficile infection. He also pointed out that use of piperacillin-tazobactam and meropenem had been low before the shortage, and described gentamicin as a cornerstone of the SAPG approach, saying that there was strong guidance for its safe use..

But he raised concerns about unreliable supply chains for important medicines. “Drug shortages in general have become a thorn in our side,” he said. “I am thinking particularly of drugs that we would like to use as alternatives to, say, piperacillin-tazobactam and meropenem or the carbapenem antibiotics.”

But Seaton said he would describe the situation as an inconvenience rather than a crisis. “There are always alternatives to this antibiotic,” he said.

While a document from Luton and Dunstable University Hospital seen by the Observer said the piperacillin-tazobactam shortage was expected to last until at least July, the document from the SAPG said they had been advised stock constraints were likely until September.

The latter also suggested the shortage might offer a silver lining, presenting a chance to improve control on how the medication is used to reduce the likelihood of resistance.
                         
According to Howard, the factory in China was now back in full production, but it might take months before the global supply chain recovered completely.
 
Ultimately, said Howard, action needed to be taken to avoid a repeat situation in the future. “We need to ensure that we use a broader range of antibiotics in our hospitals, so that if there is a global supply problem, it doesn’t have such a large impact,” he said.