Amoxicillin use linked to diarrhea and thrush

Researchers have found that taking the common antibiotics amoxicillin and amoxicillin-clavulanic acid can result in symptoms of diarrhea and candidiasis, also known as thrush. Not only that, but these adverse effects could also be under-reported, leading to a high prevalence of prescriptions.

In a recent survey study of family physicians in the UK, 55% reported feeling under pressure from patients to prescribe antibiotics.

Amoxicillin is a widely used antibiotic that belongs to the penicillin group of drugs. It is the most commonly prescribed antibiotic for respiratory infections such as bronchitis and is often prescribed alongside clavulanic acid.

However, the benefits provided by antibiotics in the treatment of respiratory infections can be marginal. 

Amid growing concern about the spread of antibiotic resistance, it is important that physicians only prescribe these drugs after carefully weighing the benefits and harms.

In fact, the root cause of antibiotic resistance is the overuse of antibiotics, and therefore these drugs should not be prescribed when the benefits do not outweigh the harms.

For their study, published in the Canadian Medical Association Journal (CMAJ), researchers conducted a review of controlled trials to assess the potential harms of amoxicillin use, in order to further inform doctors of the risks and benefits of these antibiotics.

"One way to reduce antibiotic prescribing in primary care is to explain to patients how little these drugs help for many common infections and to apply a process of shared decision-making during the consultation," write the authors.

Adverse effects found but potentially under-reported

A total of 45 trials were included in the review. Of these, 27 involved amoxicillin, 17 involved amoxicillin-clavulanic acid and one involved both drugs. These trials featured a total of 10,519 participants. Of these, 4,280 people received amoxicillin, 1,005 received amoxicillin-clavulanic acid and 5,234 received a placebo.

Antibiotics were prescribed for a range of situations (with some overlap) within the trials:

• Primary care - 33% (15 studies)
• Dental care - 20% (9 studies)
• Treatment - 56% (25 studies)
• Prevention - 20% (20 studies).

In their systematic review, the researchers found that almost twice as many people receiving amoxicillin had diarrhea compared with participants receiving placebo. Diarrhea was more than three times as likely among participants receiving amoxicillin-clavulanate. An association was also observed between candidiasis and amoxicillin-clavulanic acid use.

However, the number of reported harms were fewer than the authors expected, following clinical anecdotal experience and observationally derived data. These sources had previously reported rashes and gastrointestinal disturbances as common harms.

Harms were deemed to be poorly reported, leading the authors to conclude that their true incidence could be higher. Only 25 of the studies assessed included information on harms, "which led us to suspect that their authors simply did not collect such information or, if they did, failed to publish it," write the authors.

Under-reporting 'tilts the balance' of benefits and harms

"Under-reporting of harms in trials remains widespread," they continue, "and until that problem is addressed, under-reporting will flow to systematic reviews and other evidence syntheses such as guidelines."

The important consequence of under-reporting harms is the tilting of the balance of benefits and harms towards amoxicillin.

A limitation of the study acknowledged by the authors is that all the trials that were assessed measured efficacy rather than harm as their primary outcome. The authors say they hope as further studies are conducted, better estimates regarding harms and amoxicillin become available.

Despite this limitation, the authors believe that their findings could be of assistance to clinicians discussing the potential harms caused by common antibiotics, along with their general lack of efficacy in treating respiratory infections. The study's results may be of particular use to clinicians who feel under pressure from their patients to prescribe antibiotics.

In a related commentary, another team of researchers at the Norwich Medical School, University of East Anglia, UK, states that both physicians and patients need to be wary about the lack of information regarding potential adverse effects from amoxicillin:

"Amoxicillin has been widely used for decades, and it seems shameful that data on harms are missing from so many trials. For this drug, clinicians and patients must not construe 'absence of evidence of harm' to be the same as 'evidence of absence of harm.'"

References:

1. Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication, M. Gillies, et al., CMAJ, doi:10.1503/cmaj.140848, published online 17 November 2014, abstract.
2. If nothing happens, is everything all right? Distinguishing genuine reassurance from a false sense of security, Yoon Kong Loke, et al., CMAJ, doi:10.1503/cmaj.141344, published online 17 November 2014, extract.
3. CMAJ news release, accessed 17 November 2014.