By 1945, with penicillin heralding the dawn of antibiotic therapy, Sir Alexander Fleming had warned ‘that the high public demand of antibiotics would determine an “era of abuse”; this eventually became a reality’ (Lobanovska and Pilla, 2017). Further confirmation came this year when the European Centre for Disease Prevention and Control (ECDC) reported that data for 2021 from the World Health Organization's European Region showed that ‘33% of the countries reported resistance percentages of 25% or higher in K. pneumoniae. Carbapenem resistance was also common in Pseudomonas aeruginosa and Acinetobacter species, and at a higher percentage than in K. pneumoniae’ (ECDC, 2023).
To mitigate such challenges while promoting antibiotic stewardship, alternative antibiotic-free approaches to bacterial infections are being explored. For example, Costa-Pinta et al (2021), in addressing prosthetic joint infection involving implanted prostheses – often necessitating prosthetic removal and antibiotic administration – consider the introduction of natural antimicrobial compounds like chitosan into prostheses: ‘Chitosan is a potential valuable biomaterial presenting properties such as biocompatibility, biodegradability, low immunogenicity, wound healing ability, antimicrobial activity, and anti-inflammatory potential.’
Garaiova et al (2023) note that probiotics are ‘live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.’ A Cochrane Review of probiotics for preventing urinary tract infections (UTIs) in adults and children found ‘limited information on harm and mortality with probiotics and no evidence on the impact of probiotics on serious adverse events’, although available evidence could not rule out fewer or more recurrent UTIs in women with recurrent UTI who took prophylactic probiotics (Schwenger et al, 2015).
However, Sihra et al (2018) cite another meta-analysis suggesting that probiotics were safe and effective in preventing recurrent UTIs, ‘but a definitive recommendation could not be made owing to the small numbers of patients and studies involved.’ And while acknowledging that ‘[t]he use of well-characterized strains of Lactobacillus seems promising, … larger trials are required in order to enable firm conclusions to be made regarding their use’ (Sihra et al, 2018).
More encouragingly, a recent report from Cannizzaro et al (2023) describes the application of probiotics in the treatment of periodontal disease. A 54-year-old woman with McArdle's disease – sufferers from which can experience inter alia pain or fatigue while making repetitive movements like chewing or toothbrushing – was diagnosed with generalised periodontitis. The patient was advised on oral hygiene and given probiotic-enriched toothpaste and mouthwash to promote a rebalancing of the oral microbiota. After 60 days, improvements included her full mouth bleeding score changing from 48–15% and the ‘full mouth plaque score from 73% to 15%’ (Cannizzaro et al, 2023).
A further possible benefit of probiotic use has recently been demonstrated in addressing the incidence and duration of episodes of upper respiratory tract infections (URTIs) in children. In a double-blind, randomised, parallel-group, placebo-controlled study of 171 healthy school children aged 3–10 years, Garaiova et al (2021) describe how 86 children received a probiotic-based supplement together with low-dose vitamin C daily for 6 months (85 received a placebo). The intervention contained a multi-strain probiotic comprising Lactobacillus acidophilus, Bifidobacterium bifidum and Bifidobacterium animalis. The incidence of coughing was significantly lower by 16% among children receiving the intervention compared to placebo; there was a significantly lower risk of experiencing five different URTI-related symptoms in one day in the intervention group; and school absenteeism and antibiotic use were significantly reduced among children in the intervention group.
Expanding on this study and acknowledging that antibiotic prescription rates for children with acute illnesses in primary healthcare are high, Garaiova et al (2023) assessed the effect of daily supplementation with their multi-strain probiotic plus low-dose vitamin C on the number of antibiotic prescriptions issued by paediatricians. They found that whereas 40.6% children in the placebo group received oral antibiotic prescriptions for any infections, this fell to 29.1 % children in the intervention group, asserting that ‘[t]he combination of a multi-strain probiotic plus low-dose vitamin C may offer a safe and an inexpensive means of reducing the antibiotic prescription and contribute to the management strategies to combat antibiotic resistance’ (Garaiova et al, 2023). However, the authors also acknowledge the need for further studies to confirm their findings and to assess the impact of probiotic interventions on gut microbiota and antibiotic resistance.
Might one speculate that Fleming's antibiotic ‘era of abuse’ could be – slowly – coming to an end?