Amikacin

證據等級: L5

預測適應症: 10 個

Amikacin: From Gram-Negative Bacterial Infections to Paratyphoid Fever

One-Sentence Summary

Amikacin is a broad-spectrum aminoglycoside antibiotic, internationally established for the treatment of serious infections caused by gram-negative organisms (including resistant Pseudomonas aeruginosa and Enterobacteriaceae), though it is not currently licensed in the UK. The TxGNN model predicts it may be effective for Paratyphoid Fever, with 0 clinical trials and 12 publications currently supporting this direction. The overall evidence base is preclinical and observational in nature, with published data largely drawn from salvage-therapy case reports and antibiogram studies in multi-drug resistant enteric fever.

Quick Overview

Item	Content
Original Indication	Not currently licensed in the UK; internationally used for serious gram-negative bacterial infections
Predicted New Indication	Paratyphoid Fever
TxGNN Prediction Score	99.82%
Evidence Level	L4
UK Market Status	Not marketed
Number of Marketing Authorisations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available within this Evidence Pack. Based on known information, Amikacin is a semi-synthetic aminoglycoside derived from kanamycin; its bactericidal efficacy against serious gram-negative bacterial infections has been established internationally, and mechanistically it may be applicable to Paratyphoid Fever.

Paratyphoid fever is caused by Salmonella enterica serovars Paratyphi A, B, and C — all gram-negative organisms. Aminoglycosides such as amikacin achieve bactericidal activity by binding irreversibly to the 30S ribosomal subunit, inducing mRNA misreading and inhibiting protein synthesis — a mechanism directly applicable to these pathogens. The biological plausibility is therefore sound: PMID 2516600 (1989) directly reports amikacin use in paratyphi B infections resistant to classical first-line agents (ampicillin, chloramphenicol, co-trimoxazole), while PMID 9459410 (1997) describes successful rescue therapy with amikacin in a newborn with quinolone-resistant S. Paratyphi B meningitis.

However, significant pharmacological constraints limit first-line applicability. Aminoglycosides have negligible oral bioavailability and require parenteral (intramuscular or intravenous) administration, which limits their utility in community settings. Furthermore, S. Paratyphi has a partially intracellular lifecycle, and aminoglycosides penetrate intracellular compartments poorly, reducing their efficacy compared to fluoroquinolones or third-generation cephalosporins. Amikacin therefore represents a salvage option for extensively drug-resistant (XDR) or quinolone-resistant paratyphoid rather than a first-line repurposing candidate.

Clinical Trial Evidence

Currently no related clinical trials registered (ClinicalTrials.gov, ICTRP, EU CTR searched; 0 results).

Literature Evidence

PMID	Year	Type	Journal	Key Findings
2516600	1989	Retrospective Clinical Study	Mikrobiyoloji Bulteni	Treatment and antibiogram results in 48 paediatric patients with S. Paratyphi B infection resistant to classical agents; amikacin evaluated as an alternative antibiotic
18383953	2007	Prospective Cohort	J Indian Medical Association	Antibiotic sensitivity patterns of S. typhi and S. paratyphi in 145 blood culture-positive enteric fever cases in children under 18 years; aminoglycoside susceptibility documented
9459410	1997	Case Report	Journal of Infection	Quinolone-resistant S. Paratyphi B meningitis in a neonate; amikacin employed as rescue therapy following fluoroquinolone treatment failure
10505326	1999	Case Report	Pediatric Hematology and Oncology	Acalculous cholecystitis due to S. Paratyphi B in a 9-year-old with acute leukaemia; successfully treated with cefepime and amikacin combination
17337835	2007	Case Series	Indian Journal of Pediatrics	Paratyphoid sepsis (multidrug-susceptible S. Paratyphi A) in a neonate; microbiological and clinical management including antibiotic therapy described
26905550	2014	Antibiogram Study	JNMA (Nepal Medical Association)	Antimicrobial susceptibility profiles of blood culture isolates including Salmonella spp. at a teaching hospital; amikacin susceptibility data presented to guide empiric therapy
27407999	2007	Retrospective Study	Medical Journal, Armed Forces India	In vitro susceptibility of S. typhi and S. Paratyphi A isolates to multiple antibiotics including amikacin; reemergence of chloramphenicol sensitivity noted
8354556	1993	Microbiological Study	Indian J Pathology & Microbiology	63/280 (21.9%) MDR S. typhi strains resistant to chloramphenicol/ampicillin/co-trimoxazole but fully sensitive to aminoglycosides (including amikacin) and ciprofloxacin
14596347	2003	Epidemiological Study	New Microbiologica	Epidemiological surveillance of S. typhi and S. paratyphi in Jordan, 1988–2000; contextual data on regional burden and antibiotic resistance patterns
16410091	2006	Case Series	Journal of Pediatric Surgery	Successful management of Salmonella-associated splenic abscess in 4 paediatric patients using percutaneous drainage combined with antibiotics; aminoglycoside use described

UK Market Information

Amikacin is not currently licensed in the United Kingdom. There are no MHRA marketing authorisations on record, and the drug is not listed as a licensed product in the BNF for UK use.

Note for clinicians: Amikacin sulfate (e.g., Amikin®) is licensed in other jurisdictions and is available internationally for serious gram-negative infections. Use in the UK would require sourcing as an unlicensed medicinal product (specials) or via named-patient import, subject to current MHRA guidance on unlicensed medicines. Any clinical use should be supported by a documented clinical need and appropriate governance oversight.

Safety Considerations

Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.

Conclusion and Next Steps

Decision: Hold

Rationale: The available evidence is confined to older retrospective clinical studies, case reports, and antibiogram surveys (L4), with no registered clinical trials at any phase. Whilst biological plausibility is supported by amikacin’s documented in vitro activity against Salmonella Paratyphi and its historical use as a salvage antibiotic in drug-resistant enteric fever, the absence of prospective clinical evidence, lack of UK market authorisation, and significant pharmacological constraints (parenteral-only administration, limited intracellular penetration) do not currently justify a formal repurposing programme.

To proceed, the following is needed:

Mechanism of action data (DrugBank MOA query) to formally characterise the aminoglycoside–Salmonella interaction within the TxGNN knowledge graph
Contemporary in vitro susceptibility data for UK/European clinical isolates of S. Paratyphi to confirm maintained amikacin sensitivity in circulating strains
MHRA marketing authorisation pathway assessment or unlicensed use framework prior to any clinical investigation
A systematic literature review specifically focused on aminoglycosides in multi-drug resistant and extensively drug-resistant (XDR) enteric fever, to establish whether a Phase 2 proof-of-concept trial is warranted
Pharmacokinetic/pharmacodynamic modelling to evaluate dosing adequacy for systemic Salmonella infection given the intracellular reservoir challenge
Full SmPC-level safety review (nephrotoxicity, ototoxicity, neuromuscular blockade) before any clinical protocol is drafted

Disclaimer: This report is for research purposes only and does not constitute medical advice. Drug repurposing candidates require clinical validation before application. All findings should be interpreted in the context of available evidence and relevant clinical guidelines.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.