Control of Klebsiella pneumoniae Infection in Mice by Using Dissolving Microarray Patches Containing Gentamicin

Rodgers, Aoife M.; McCrudden, Maeliosa; Courtenay, Aaron J.; Kearney, Mary‐Carmel; Edwards, Katherine L; Ingram, Rebecca J.; Bengoechea, José A.; Donnelly, Ryan F.

doi:10.1128/aac.02612-18

Cited by 12 publications

(11 citation statements)

References 23 publications

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“…IV antibiotic administration is not as convenient as oral therapy however, necessitating specially trained personnel and giving rise to issues such as needle-phobia and introduction of infection. More user-friendly parenteral delivery systems may have a role to play in this area, such as microneedle arrays, which have already demonstrated potential for this purpose. , …”

Section: Resultsmentioning

confidence: 99%

Antibiotic Therapy and the Gut Microbiome: Investigating the Effect of Delivery Route on Gut Pathogens

et al. 2021

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The contribution of the gut microbiome to human health has long been established, with normal gut microbiota conferring protection against invasive pathogens. Antibiotics can disrupt the microbial balance of the gut, resulting in disease and the development of antimicrobial resistance. The effect of antibiotic administration route on gut dysbiosis remains under-studied to date, with conflicting evidence on the differential effects of oral and parenteral delivery. We have profiled the rat gut microbiome following treatment with commonly prescribed antibiotics (amoxicillin and levofloxacin), via either oral or intravenous administration. Fecal pellets were collected over a 13-day period and bacterial populations were analyzed by 16S rRNA gene sequencing. Significant dysbiosis was observed in all treatment groups, regardless of administration route. More profound dysbiotic effects were observed following amoxicillin treatment than those with levofloxacin, with population richness and diversity significantly reduced, regardless of delivery route. The effect on specific taxonomic groups was assessed, revealing significant disruption following treatment with both antibiotics. Enrichment of a number of groups containing known gut pathogens was observed, in particular, with amoxicillin, such as the family Enterobacteriaceae. Depletion of other commensal groups was also observed. The degree of dysbiosis was significantly reduced toward the end of the sampling period, as bacterial populations began to return to pretreatment composition. Richness and diversity levels appeared to return to pretreatment levels more quickly in intravenous groups, suggesting convenient parenteral delivery systems may have a role to play in reducing longer term gut dysbiosis in the treatment of infection.

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Section: Resultsmentioning

confidence: 99%

Antibiotic Therapy and the Gut Microbiome: Investigating the Effect of Delivery Route on Gut Pathogens

et al. 2021

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“…Bacterial resistance problems have occurred in different parts of the body. Accordingly, several drug delivery systems have been discovered with various routes to deliver antimicrobial agents to overcome this resistance issue [ 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 ].…”

Section: Drug Delivery Approaches Via Different Routes To Overcome Antimicrobial Resistancementioning

confidence: 99%

“…In vitro transdermal delivery showed that microneedles were able to deliver around 4.45 mg of gentamicin after 6 h. In an in vivo study using rats, it was found that dissolving microneedles could deliver gentamicin transdermally at therapeutic levels. Furthermore, Rodgers et al evaluated the in vivo efficacy of gentamicin loaded dissolving microneedles in a murine model of K. pneumoniae bacterial infection [ 172 ]. The microneedles were applied to murine ears.…”

Section: Drug Delivery Approaches Via Different Routes To Overcome Antimicrobial Resistancementioning

confidence: 99%

Pharmaceutical Approaches on Antimicrobial Resistance: Prospects and Challenges

et al. 2021

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The rapid increase in pathogenic microorganisms with antimicrobial resistant profiles has become a significant public health problem globally. The management of this issue using conventional antimicrobial preparations frequently results in an increase in pathogen resistance and a shortage of effective antimicrobials for future use against the same pathogens. In this review, we discuss the emergence of AMR and argue for the importance of addressing this issue by discovering novel synthetic or naturally occurring antibacterial compounds and providing insights into the application of various drug delivery approaches, delivered through numerous routes, in comparison with conventional delivery systems. In addition, we discuss the effectiveness of these delivery systems in different types of infectious diseases associated with antimicrobial resistance. Finally, future considerations in the development of highly effective antimicrobial delivery systems to combat antimicrobial resistance are presented.

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“…As DMN are fabricated from water-soluble, biocompatible materials that dissolve in the skin post-insertion, they overcome the generation of biohazardous sharps wastes and any material that remains on the skin may be discarded in non-sharps waste 47. Thus, this circumvents the risk of injury and disease transmission from used or contaminated needles 4…”

Section: Circumventing Vaccine Delivery Challenges: Is the Solution Imentioning

confidence: 99%

<p>Technology update: dissolvable microneedle patches for vaccine delivery</p>

Rodgers¹,

Cordeiro²,

Donnelly³

2019

MDER

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Despite vaccination representing one of the greatest advances of modern preventative medicine, there remain significant challenges in vaccine distribution, delivery and compliance. Dissolvable microarray patches or dissolving microneedles (DMN) have been proposed as an innovative vaccine delivery platform that could potentially revolutionize vaccine delivery and circumvent many of the challenges faced with current vaccine strategies. DMN, due to their ease of use, lack of elicitation of pain response, self-disabling nature and ease of transport and distribution, offer an attractive delivery option for vaccines. Additionally, as DMN inherently targets the uppermost skin layers, they facilitate improved vaccine efficacy, due to direct targeting of skin antigen-presenting cells. A plethora of publications have demonstrated the efficacy of DMN vaccination for a range of vaccines, with influenza receiving particular attention. However, before the viable adoption of DMN for vaccination purposes in a clinical setting, a number of fundamental questions must be addressed. Accordingly, this review begins by introducing some of the key barriers faced by current vaccination approaches and how DMN can overcome these challenges. We introduce some of the recent advances in the field of DMN technology, highlighting the potential impact DMN could have, particularly in countries of the developing world. We conclude by reflecting on some of the key questions that remain unanswered and which warrant further investigation before DMNs can be utilized in clinical settings.

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Control of Klebsiella pneumoniae Infection in Mice by Using Dissolving Microarray Patches Containing Gentamicin

Cited by 12 publications

References 23 publications

Antibiotic Therapy and the Gut Microbiome: Investigating the Effect of Delivery Route on Gut Pathogens

Antibiotic Therapy and the Gut Microbiome: Investigating the Effect of Delivery Route on Gut Pathogens

Pharmaceutical Approaches on Antimicrobial Resistance: Prospects and Challenges

<p>Technology update: dissolvable microneedle patches for vaccine delivery</p>

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