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 widely used for serious infections caused by susceptible Gram-negative bacteria (including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli). The TxGNN model predicts it may be effective for Paratyphoid Fever, with 0 clinical trials and 12 publications currently supporting this direction. Evidence is largely observational and retrospective, placing this prediction at evidence level L4.

Quick Overview

Item	Content
Original Indication	Serious Gram-negative bacterial infections (septicaemia, respiratory tract infections, urinary tract infections, etc.)
Predicted New Indication	Paratyphoid Fever
TxGNN Prediction Score	99.82%
Evidence Level	L4
Singapore Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available from the data sources queried. Based on known pharmacological knowledge, Amikacin is a semi-synthetic aminoglycoside antibiotic that works by binding irreversibly to the 30S ribosomal subunit, thereby disrupting bacterial protein synthesis. Critically, Amikacin possesses a unique structural modification (an amide substituent at the 1-amino position) that confers superior stability against aminoglycoside-modifying enzymes (AMEs) — the primary resistance mechanism against other aminoglycosides such as gentamicin. This makes Amikacin effective against many strains that have developed resistance to earlier aminoglycosides.

Paratyphoid fever is caused by Salmonella paratyphi A, B, or C — Gram-negative facultative anaerobes belonging to the family Enterobacteriaceae, the very bacterial class Amikacin is designed to target. In standard clinical practice, first-line treatment of paratyphoid fever uses fluoroquinolones or third-generation cephalosporins. However, the growing global emergence of multidrug-resistant (MDR) strains — already resistant to classical agents (chloramphenicol, ampicillin, TMP-SMX) and increasingly to fluoroquinolones — creates an urgent clinical need for alternative antibiotic options. In this MDR context, Amikacin may serve as a salvage antibiotic.

The mechanistic link is therefore straightforward and biologically sound: the same 30S-ribosome inhibition that makes Amikacin effective against hospital-acquired Gram-negative infections also confers in vitro activity against Salmonella paratyphi. The available literature, though predominantly retrospective antibiogram studies rather than interventional trials, consistently confirms susceptibility of S. paratyphi to Amikacin. The key clinical caveat is that aminoglycosides have limited intracellular penetration — a relative disadvantage against a facultative intracellular pathogen — which may explain why fluoroquinolones remain preferred when they retain activity.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
10505326	1999	Case Report	Pediatric Hematology and Oncology	Acalculous cholecystitis caused by S. paratyphi B in a child with acute lymphoblastic leukemia; successfully treated with cefepime + amikacin + G-CSF — direct clinical use of Amikacin in S. paratyphi infection
2516600	1989	Case Series	Mikrobiyoloji Bulteni	48 patients with paratyphi B infection; reports antibiogram results for resistant strains and evaluates alternative antibiotic treatment outcomes
18383953	2007	Prospective Observational	Journal of the Indian Medical Association	145 blood culture-positive enteric fever cases in children <18 years; current antibiotic sensitivity pattern of S. typhi and S. paratyphi reported
17337835	2007	Case Series	Indian Journal of Pediatrics	Paratyphoid sepsis in a neonate; blood culture positive for multidrug-susceptible S. paratyphi A — highlights neonatal vulnerability and antibiotic management
9459410	1997	Case Report	The Journal of Infection	Quinolone-resistant S. paratyphi B meningitis in a newborn; underscores the clinical need for non-quinolone alternatives including aminoglycosides
30724049	2018	Cross-sectional	Pakistan Journal of Biological Sciences	Isolation and microbiological characterisation of S. paratyphi from enteric fever patients in Quetta, Pakistan; antimicrobial resistance profiles documented
27407999	2007	Retrospective	Medical Journal, Armed Forces India	In vitro susceptibility of S. typhi and S. paratyphi A in northern India; reemergence of chloramphenicol sensitivity noted, aminoglycosides retained activity
26905550	2014	Retrospective	JNMA (Nepal Medical Association)	Blood culture isolates and antibiogram from a teaching hospital; empiric antimicrobial guidance for bacteraemia including enteric fever organisms
16410091	2006	Case Series	Journal of Pediatric Surgery	4 pediatric splenic abscess cases successfully managed with percutaneous drainage plus antibiotic therapy; Salmonella-related aetiology included
14596347	2003	Cross-sectional	The New Microbiologica	Surveillance of S. typhi and S. paratyphi in Jordan (1988–2000); epidemiological baseline for enteric fever in the region

Singapore Market Information

Amikacin (DrugBank ID: DB00479) currently has no active marketing authorisations in Singapore. The drug is not registered with the Health Sciences Authority (HSA) and has no approved product listings on the Singapore market.

Note: Amikacin is widely registered in other jurisdictions (e.g., the United States, European Union, Japan, India) as an injectable antibiotic for serious Gram-negative infections. Importation or compassionate use in Singapore would require HSA approval.

Safety Considerations

Formal package insert data and HSA-approved warnings could not be retrieved for this evaluation (no Singapore registration). Based on the drug class (aminoglycoside antibiotic), the following well-established class-level safety concerns apply:

Nephrotoxicity: Aminoglycosides are concentration-dependent nephrotoxins; renal function monitoring (serum creatinine, BUN) is mandatory during therapy
Ototoxicity: Both cochlear (hearing loss) and vestibular toxicity are recognised adverse effects; audiological monitoring is recommended for prolonged courses
Neuromuscular blockade: Rare but potentially serious; caution in patients with myasthenia gravis or concurrent neuromuscular-blocking agents
Drug interactions: Additive nephrotoxicity with other nephrotoxic agents (e.g., cisplatin, vancomycin, amphotericin B, NSAIDs); additive ototoxicity with loop diuretics (e.g., furosemide)
Pregnancy / Neonatal use: Aminoglycosides cross the placenta; foetal ototoxicity has been reported with streptomycin and is a class concern

Please refer to the full package insert and international prescribing information (e.g., FDA label) for comprehensive safety information until Singapore-specific HSA data is obtained.

Conclusion and Next Steps

Decision: Hold

Rationale: Although the mechanistic basis is biologically plausible — Amikacin's 30S-ribosome inhibition is directly applicable to Salmonella paratyphi as a Gram-negative Enterobacteriaceae — the available evidence consists solely of retrospective antibiogram studies and isolated case reports (evidence level L4), with no registered clinical trials. Amikacin is not currently marketed in Singapore, and critical safety data (HSA package insert, formal contraindications) has not been retrieved.

To proceed, the following is needed:

MOA verification: Confirm Amikacin's 30S ribosome binding mechanism and AME-resistance profile via DrugBank API (DG002 remediation)
Package insert review: Download and parse the HSA or FDA/EMA package insert for formal warnings, contraindications, dosing, and monitoring requirements (DG001 remediation)
Resistance landscape assessment: Review current Salmonella paratyphi AMR data in Singapore/Southeast Asia to determine whether Amikacin retains activity against locally circulating strains
Clinical PK/PD data: Obtain data on Amikacin's intracellular penetration against facultative intracellular pathogens to address the fundamental pharmacological limitation
Registration pathway: Assess HSA requirements for Amikacin importation or registration if clinical utility is confirmed
Prospective evidence: Identify or initiate a case series or observational study capturing Amikacin use in MDR enteric fever, particularly in paediatric or immunocompromised populations where the need is greatest

⚠️ Disclaimer: This report is for research reference purposes only and does not constitute medical advice. Drug repurposing candidates require clinical validation before any therapeutic application.

Disclaimer

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