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Nitrofurantoin complication goes to trial

05 June 2020

By Marshal Ahluwalia, claims manager, Medical Protection

Mrs S was 64 years old and had a significant medical history that included rheumatoid arthritis, frequent urinary tract infections and giant cell arteritis. For a period of time she took methotrexate for her rheumatoid arthritis; the disease limited her mobility and she was morbidly obese, requiring the use of a wheelchair and care from her daughter and adult granddaughter, both of whom lived locally to her. Methotrexate was discontinued.

Mrs S was a frequent attender at her GP surgery for treatment of her medical conditions and was under the care of urologists for her frequent urinary tract infections. Urologists prescribed prophylactic nitrofurantoin 50mg, which Mrs S took each evening and had done so for a number of years.

Mrs S attended Dr B with a complaint of being a bit breathless when walking and swelling to her ankles. Dr B performed auscultation of the chest and bilateral crackles were noted but no rhonchi. Superficial phlebitis in the right lower leg was diagnosed. Dr B prescribed a short course of furosemide for 14 days and codeine for pain, and requested that Mrs S return for further examination at the end of the course.

A few days later Mrs S telephoned the surgery and spoke with Dr X, who was the GP on call that day. She informed Dr X that she was experiencing breathing problems and thought she could be suffering from cystic fibrosis. He noted she informed him that she had a cough, was breathless, felt cold and shivery and was tired. Dr X asked Mrs S to come to the surgery for a face to face consultation, and she came in later that day.

On auscultation of the chest, Dr X found adequate air entry in all areas with unilateral crackles in the left lower zone. Mrs S had had a productive cough since the previous consultation with Dr B. She was breathless and felt shivery but was apyrexial.

Dr X diagnosed a chest infection and prescribed cefalaxin 500mg. Mrs S returned to see her GP on other occasions over the next couple of months but the notes did not suggest any symptoms of chest infection, until one consultation with Dr X where the presenting symptoms were the same as two months prior. Dr X considered this to be a new presentation of a chest infection and a further course of cefalaxin was prescribed.

A few days later, Mrs S contacted an out of hours service with a complaint of shivering with a raised temperature and shortness of breath. A diagnosis of chest infection was made. Her steroid prescription was increased to 30mg daily and she was prescribed clarithromycin.

Five days later, Mrs S reattended the surgery and was advised by Dr P to continue to take the prescribed antibiotics and continue with steroid inhalers, but to add an inhaler. She was to be reviewed again the next day. Later that day, Mrs S underwent a chest x-ray.

The next day, Mrs S reattended with Dr P. The chest x-ray report was not available. The claimant was noted to “feel slightly better than last week, had cxr yesterday but no report available”. Her chest was examined and no wheeze or creps were found. Dr P requested that the claimant have her full blood count checked, a d-dimer and her U&Es checked.

Later that day Mrs S attended an out of hours clinic and was examined by another GP. She gave a history of having had a d-dimer test that afternoon, and she was tired, had a bad chest and her ankles were “always swollen”. She was noted to have had a “bad chest over last couple of weeks nil pleurisy – retrosternal pain nil haemoptysis”. Mrs S was subsequently examined by another doctor and upon examination gave a history of having three recent courses of antibiotics for a chest infection, but that she was noted to be “well perfused and hydrated SOB no cyanosis no recession good bilateral air entry – no dullness no chest pain”. A diagnosis of dyspnoea was made and the plan, in view of Mrs S’s worsening symptoms of shortness of breath and tachycardia, was of investigation for a pulmonary embolism and possible chest infection. She was subsequently admitted to hospital.

Upon referral from her local hospital, Mrs S attended the Emergency Department at a different hospital later that day. The working diagnosis was a lower respiratory tract infection with abnormal liver function test results and Mrs S was to have an ultrasound scan of her abdomen, her LFTs were to be repeated and the nitrofurantoin was continued.

Three days later, there was the impression of pulmonary fibrosis secondary to rheumatoid arthritis and methotrexate therapy was considered; Mrs S was sent for respiratory referral. Nitrofurantoin was continued.

A CT scan was undertaken two days later. The scan was reported as showing widespread fibrosis in the chest. The appearance was consistent with acute nitrofurantoin lung. Nitrofurantoin was stopped by the respiratory team as it was felt to be the causative agent for the fibrosis.

Mrs S was discharged from hospital a week later but remained under the care of the respiratory team.

Three months later, concern was raised about the aetiology of the fibrosis. Radiology was considered at an MDT meeting and it was agreed that the clinical and radiological picture would fit with sub-acute nitrofurantoin pulmonary toxicity.

After the nitrofurantoin was stopped, the claimant’s condition improved and she was discharged home on trimethoprim with care from family members.

The claim

Mrs S instructed solicitors to bring a negligence claim, alleging that her nitrofurantoin should have been stopped by the GPs when she originally presented and, had that occurred, she would not have experienced breathlessness necessitating hospital admission. She claimed that she developed dysfunctional breathing and/or hyperventilation syndrome as a result of the alleged negligence of the two GPs, Dr X and Dr B, which had adversely affected her mobility, weight, quality of life and ability to work.

Mrs S claimed that her GPs should have been aware of the link between nitrofurantoin and pulmonary fibrosis and their failure to consider this link when assessing her was a breach of their duty of care. She claimed that based upon her presenting symptoms she should have been referred for an urgent chest x-ray. Upon receipt of that chest x-ray, Mrs S claimed, it would have shown worrying signs and the reasonable GP would have stopped the nitrofurantoin prescription immediately. She claimed this would have avoided the impact on her weight, quality of life, mobility and income.

How Medical Protection helped

Dr X was a member of Medical Protection and we assembled a legal team to assist him. Proceedings were also brought against Dr B, who was separately represented.

Evidence from a GP expert was supportive of Dr X’s initial care of Mrs S but questionable of his care later on, when the hypothetical x-ray could have been received back at the practice and shown evidence of fibrosis.

Evidence was also obtained from a consultant respiratory physician to comment upon Mrs S’s likely treatment and impact of that treatment had it been provided earlier, and from a radiologist on what the hypothetical x-ray would have shown. Additional expert evidence was obtained from a rheumatologist.

The claim was strongly defended on behalf of Dr X. It was also strongly defended by Dr B.

The experts for the defendants and Mrs S met to discuss the case and the radiologists agreed it was impossible to say what an urgent x-ray after the first consultation would have shown. They agreed that any x-ray taken following the later consultation would have shown similar but less worrying signs than those revealed in the CT scan conducted in hospital.

The GP experts agreed that the reasonable GP may not be aware of the link between nitrofurantoin and pulmonary fibrosis. However, they disagreed on Mrs S’s likely presenting symptoms during her initial GP consultations, and on what signs and symptoms would be present if she had presented with a chest infection or a reaction to nitrofurantoin adversely affecting the lungs.

Despite it being diagnosed by her treating clinicians, the parties’ experts agreed that on the balance of probabilities, Mrs S did suffer from nitrofurantoin induced lung toxicity but did not have pulmonary fibrosis; she had suffered from pneumonitis, which had resolved after discontinuance of the nitrofurantoin. Any residual breathing problems after resolution of the pneumonitis was due to the pre-existing rheumatoid arthritis.

The claim proceeded to trial.

The outcome

The day before the trial commenced, Mrs S sought to amend her pleaded claim against Dr B, claiming that Dr B should have investigated Mrs S for heart failure based upon her initial presentation. She had chosen not to take the point until the day before the trial.

The proposed amendment was opposed as it was considered prejudicial to the defendants – as they had not been able to provide witness or expert evidence in response to the new allegations, and it was coming extremely late and could impact upon the trial.  The judge accepted this and the proposal to amend the claim was rejected.

The claimant discontinued her claim against both defendants on the afternoon of the second day of trial.

Indemnity costs were ordered in this case to penalise Mrs S for the poor way her claim had been handled and conducted.

New Zealand perspective

If this case had occurred in New Zealand and Mrs S had wished to seek financial compensation, she would have been advised to ask her doctor to submit an ACC treatment injury claim on her behalf, as there is a bar on suing for personal injury in this country. ACC treatment injury claims cover injuries caused to patients in the course of treatment from registered health professionals. If accepted, ACC may pay or contribute to the cost of treatment, rehabilitation and compensation. In order to have such a claim accepted, the injury must have resulted in physical harm or damage to the patient, it must have been caused by that treatment and the injury must not be a necessary part or an ordinary consequence of treatment. An adverse drug reaction would often be considered an appropriate basis for a treatment injury claim as a rare drug reaction would not be considered an ordinary consequence of treatment. In 2017/2018 there were 319 ACC treatment injury claims accepted due to medication adverse events, with a total cost of all those claims coming to $7,405,746.

In this case it appears the patient did suffer from a physical injury, in that she had evidence of a pneumonitis. As ACC is a no-fault scheme, the patient does not have to show any negligence or error on the part of the health professionals in order to obtain cover. As Mrs S was treated in a public hospital and the physical injury appeared to resolve, her compensation may only have been a contribution to lost earnings or treatment related expenses and is likely to have been only a small amount. It is also salient to note that if the condition was thought to be caused or exacerbated by her underlying health conditions, her compensation would have been reduced accordingly.

Learning points

While GPs should be aware of the potential link between nitrofurantoin and breathing problems, there is a reasonable body of GPs who would not have known of that link back when this case occurred. Any such diagnosis is unlikely to be made by a GP and is most likely to be made by respiratory physicians in a hospital setting.

The British National Formulary offers the following guidance that is applicable to patients on long-term nitrofurantoin: “In adults: on long-term therapy, monitor liver function and monitor for pulmonary symptoms, especially in the elderly (discontinue if deterioration in lung function).”