Summary: Fluoroquinolone antibiotics, such as Levofloxacin and Ciprofloxacin, appear to increase the risk of peripheral neuropathy by 47%. However, there is no significant increased risk of developing neuropathy associated with amoxicillin use.

Source: University of Dundee

Research from the University of Dundee has shown that a commonly used class of antibiotics may increase a patient’s risk of suffering a serious and potentially permanent form of nerve damage by almost 50%.

Peripheral neuropathy has long been recognised as a potential side effect of fluoroquinolone antibiotics but it was not known how strong this association was and how it could be affected by the length of treatment, or by age and gender.

Researchers led by Dr Daniel Morales, of the University’s School of Medicine, looked at a database of 1.3 million adults issued one or more prescriptions of fluoroquinolone or amoxicillin-clavulanate antibiotics with no diagnosis of peripheral neuropathy at the outset of treatment.

They found that current use of systemic fluoroquinolone antibiotics appeared to increase the risk of peripheral neuropathy by 47%, causing an additional 2.4 cases per 10 000 patients per year of treatment. A person prescribed with amoxicillin-clavulanate were not significantly more likely to experience peripheral neuropathy.

The risk was higher for men and rose with age and with the length of fluoroquinolone treatment. A peripheral neuropathy diagnosis remained more likely to be diagnosed for up to six months after the fluoroquinolone prescription.

Older men, the group most likely to experience the condition after taking a 28-day course of fluoroquinolones, were said to have a 1 in 34,000 chance of doing so. While the absolute risk of a peripheral neuropathy diagnosis remained low, Dr Morales said the findings should still be considered as one of the different potential side effects before prescribing antibiotics.

“The safety of fluoroquinolone antibiotics has received a lot of attention regarding their potential to cause long-term side effects in some people,” he said. “One of these is peripheral neuropathy where nerves, most commonly affecting the lower limbs, can be affected, leading to numbness, pain, or problems with balance.

“Fluoroquinolones are effective antibiotics but health care professionals should recognise that peripheral neuropathy may rarely occur following fluoroquinolone therapy. Antibiotic stewardship is critically important to ensure these valuable medicines are used appropriately.

“We observed that treatment with fluoroquinolones could increase the risk of peripheral neuropathy by around 50% and that this risk may last for up to 6 months following treatment. It was interesting to observe that the results varied according to the length of antibiotic treatment and our findings suggest that risk may not be the same for everyone.”

When health professionals suspect that a medicine causes an adverse reaction they are encouraged to report these cases to medicine regulatory agencies. Case reports previously identified peripheral neuropathy as a potential side effect of treatment with fluoroquinolone antibiotics. However, further studies confirming or refuting this risk were limited, in particular, those aimed at quantifying risk and examining how it may vary among different people.

Dr Morales’ research has been published in the latest edition of the journal JAMA Neurology.

About this neuroscience research article

Source:

University of Dundee

Media Contacts:

Grant Hill – University of Dundee

Image Source:

The image is in the public domain.

Original Research: Closed access

“Association Between Peripheral Neuropathy and Exposure to Oral Fluoroquinolone or Amoxicillin-Clavulanate Therapy”. Daniel Morales, PhD; Alexandra Pacurariu, PhD; Jim Slattery, MSc; Luis Pinheiro, MSc; Patricia McGettigan, MD; Xavier Kurz, MD, PhD.

JAMA Neurology.. doi:10.1001/jamaneurol.2019.0887

Abstract

Association Between Peripheral Neuropathy and Exposure to Oral Fluoroquinolone or Amoxicillin-Clavulanate Therapy

Importance Peripheral neuropathy has been associated with systemic fluoroquinolone exposure, but risk has been poorly quantified.

Objective To calculate relative and absolute risk estimates for the association of fluoroquinolone exposure with peripheral neuropathy and to examine how risk may be affected by timing of fluoroquinolone exposure and by other risk factors.

Design, Setting, and Participants This nested case-control study used anonymized data from all patients routinely registered with general practices in The Health Improvement Network database, a large primary care population database in the United Kingdom, from January 1, 1999, to December 31, 2015. Data analyses were conducted January 8, 2018. The cohort consisted of 1 338 900 adults issued 1 or more prescriptions of fluoroquinolone (34.3%) or amoxicillin-clavulanate (65.7%) antibiotics. Adults with incident peripheral neuropathy were matched (on age, sex, general practice, and calendar time) with up to 4 controls by using incidence density sampling selected from a cohort prescribed oral fluoroquinolone or amoxicillin-clavulanate antibiotics. Incidence rate ratios of peripheral neuropathy were calculated for fluoroquinolone and for amoxicillin-clavulanate exposure and compared with nonexposure among patients without diabetes, with sensitivity analyses testing the consistency of the results. Population mean–adjusted rate differences were then estimated, including the number needed to harm for various durations of fluoroquinolone therapy.

Exposures Current and cumulative exposure to oral fluoroquinolone or amoxicillin-clavulanate antibiotics.

Main Outcomes and Measures Incident peripheral neuropathy cases recorded in electronic medical records.

Results In total, 5357 patients with incident peripheral neuropathy (mean [SD] age, 65.6 [14.7] years; 2809 women [52.4%]) were matched to 17 285 controls (mean [SD] age, 64.4 [15.2] years; 9485 women [54.9%]) without diabetes. Current oral fluoroquinolone exposure was associated with an increased relative incidence of peripheral neuropathy compared with nonexposure (adjusted incident rate ratio, 1.47; 95% CI, 1.13-1.92). Risk increased by approximately 3% for each additional day of current fluoroquinolone exposure and persisted for up to 180 days following exposure. No significant increased risk was observed with oral amoxicillin-clavulanate exposure. The absolute risk with current oral fluoroquinolone exposure was 2.4 (95% CI, 1.8-3.1) per 10 000 patients per year of current use. The number needed to harm for a 10-day course was 152 083 patients (95% CI, 117 742-202 778) and was greatest among men and among patients older than 60 years.

Conclusions and Relevance The results of the present study suggested that oral fluoroquinolone therapy was associated with an increased risk of incident peripheral neuropathy that may depend on the timing of the exposure and the cumulative dose. Health care professionals should consider these potential risks when prescribing fluoroquinolone antibiotics.

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