This article discusses the growing threat of antibiotic resistance. It also highlights lolamicin's potential in treating multidrug-resistant infections without the typical side effects of broad-spectrum antibiotics.

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Current antibiotics often lack specificity, affecting both harmful and beneficial bacteria in the gut, which increases the risk of secondary infections and contributes to the development of antibiotic resistance. This non-selective disruption has also been linked to longer-term health issues, including colon cancer and irritable bowel syndrome.[1][2][3]

At the same time, the indiscriminate use of antibiotics has also given rise to life-threatening multidrug-resistant gram-negative bacteria—it has been estimated that by the year 2050, there will be over 10 million annual fatalities due to antimicrobial resistance (AMR).[4]

 Antibiotic resistance poses a significant threat to global health, particularly with the rising prevalence of multidrug-resistant (MDR) gram-negative bacteria.

Given these challenges, developing selective antibiotics that spare the gut microbiota has become a critical focus in the fight against antibiotic resistance. But lolamicin, a new and novel antibiotic, presents a promising solution to this growing threat.[5]

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Challenges with traditional antibiotics

Antibiotic-associated diarrhoea (AAD) remains a prevalent issue stemming from antibiotic use, with disruptions to gut microbiota leading to overgrowth of pathogens like Clostridioides difficile, Klebsiella, Staphylococcus, and Candida.[6]

AMR is a growing threat to global health, as is the rising prevalence of MDR—the latter being a major cause of nosocomial infections. 

The CDC has identified several high-risk AMR pathogens, including:

• MDR Pseudomonas aeruginosa
• Carbapenem-resistant Enterobacterales (CRE) and Acinetobacter
• Methicillin-resistant Staphylococcus aureus (MRSA)
• Vancomycin-resistant Enterococcus (VRE)
• Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales
• Emerging drug-resistant fungal infection Candida auris (C. auris).[7] 

Four out of these seven infections are gram-negative, requiring heavy antibiotics with the potential to disrupt the normal flora of the gastrointestinal tract.

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Lolamicin: A novel, selective antibiotic

A recent study published in Nature introduces lolamicin, a novel antibiotic specifically targeting gram-negative bacteria without disrupting beneficial gut flora, which is a welcome option given the current limitations of antibiotic therapies.[5]

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Mechanism of action and selectivity

1. Lolamicin uniquely targets the lipoprotein transport system (Lol pathway), essential for the survival of gram-negative bacteria, as it facilitates the movement of lipoproteins between their inner and outer membranes.
2. This pathway is absent in gram-positive bacteria, which lack the dual-membrane structure and only possess a single cellular membrane.
3. As a result, lolamicin offers double selectivity—attacking pathogenic gram-negative bacteria while preserving gut commensals, thus minimising collateral damage—overcoming a key limitation of traditional antibiotics.[1][5]

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Preclinical efficacy and safety

1. Lolamicin has demonstrated robust efficacy in preclinical trials, including multiple experimental models of acute pneumonia and septicemia. It selectively targeted multidrug-resistant strains of E. coli, Klebsiella pneumoniae, and Enterobacter cloacae, achieving up to 90% bactericidal activity in cell cultures.
2. In vivo, orally administered lolamicin improved survival rates in septicemia models, with a 70% survival rate in the treated experimental model. Notably, lolamicin-treated experimental model exhibited significantly lower C. difficile colonisation than those receiving broad-spectrum antibiotics like amoxicillin or clindamycin.[1]
3. While these preclinical findings are promising, lolamicin is still in early-stage development. Human clinical trials are necessary to confirm its efficacy and safety profile and evaluate the potential for resistance development against this novel mechanism.

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Interim strategies for gut health during antibiotic use

While waiting for microbiome-sparing antibiotics like lolamicin to reach clinical use, there are immediate steps that can be taken to mitigate the impact of conventional antibiotics on gut health. Consider the following:

1. Antimicrobial stewardship (AMS)

Stewardship entails using the right antibiotic at the right dose, drug route, and duration, and de-escalating therapy promptly when appropriate. According to a review from Cureus, this approach both preserves antibiotic efficacy and minimises gut microbiota disruption.[8]

2. Dietary interventions

High-fibre diets support the rapid recovery of healthy gut flora post-antibiotic treatment. As noted in a 2022 study on American adults, consuming a high-fibre diet was associated with a lower risk of AMR and a lower abundance of Clostridium overgrowth.[9]

3. Probiotics and fermented foods

The role of probiotics during antibiotic use shows mixed results:

1. A 2024 trial found that probiotics containing Lactobacillus, Bifidobacterium, and Saccharomyces strains helped maintain gut microbiome diversity, increased Bacteroides, reduced enterobacteria, and decreased AMR genes in adult patients on antibiotics.[10]
2. Similar outcomes were observed in a 2024 study published in JAMA Network Open, involving pediatric patients on antibiotic therapy who were given a multispecies probiotic with eight bacterial strains; compared with controls, the probiotic temporarily boosted microbial diversity—but the improvement was minor and results short-lived.[11]

However, consuming probiotics from natural sources like yoghurt, kefir, and sauerkraut is a practical and beneficial way to support gut balance during and after antibiotic treatment.

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Disclaimer: This story is contributed by Alpana Mohta and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.