Amikacin

Evidence Level: L4

Predicted Indications: 10

Amikacin
Amikacin: From Bacterial Infections (Pneumonia, Meningitis, Cholangitis) to Paratyphoid Fever

## Pharmacist Assessment Report

Amikacin: From Bacterial Infections (Pneumonia, Meningitis, Cholangitis) to Paratyphoid Fever

One-Sentence Summary

Amikacin is an aminoglycoside antibiotic, originally used for serious Gram-negative bacterial infections such as pneumonia, meningitis and cholangitis. The TxGNN model predicts it may be effective for paratyphoid fever, but there are currently no registered clinical trials and only 8 publications (mostly epidemiology and antibiogram surveys, with no direct amikacin efficacy data), so the evidence is weak.

Quick Overview

Item	Content
Original Indication	Bacterial pneumonia, Pseudomonas aeruginosa infection, cholangitis, bacterial meningitis and other bacterial infections (from the knowledge graph; the Singapore licence records do not include approved indication text)
Predicted New Indication	Paratyphoid fever
TxGNN Prediction Score	99.82%
Evidence Level	L4
Singapore Market Status	✓ Marketed
Number of Registrations	2
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, amikacin is an aminoglycoside that inhibits the bacterial 30S ribosomal subunit and has broad Gram-negative activity. Its efficacy in Gram-negative infections is established, so activity against Salmonella Paratyphi is plausible.

There are important limitations. Salmonella is a facultative intracellular pathogen, and aminoglycosides penetrate cells poorly. Standard enteric fever therapy relies on fluoroquinolones, azithromycin or third-generation cephalosporins, so amikacin has no clear role. The high TxGNN score therefore reflects knowledge-graph similarity rather than demonstrated clinical benefit.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
10505326	1999	Case report	Pediatr Hematol Oncol	Child with leukaemia and acalculous cholecystitis due to S. Paratyphi B, successfully treated with cefepime, amikacin and granulocyte support (combination therapy)
2516600	1989	Case series	Mikrobiyol Bul	48 paratyphi B patients with strains resistant to classical therapy; antibiotic choices and outcomes reported
18383953	2007	Cohort	J Indian Med Assoc	145 paediatric enteric fever cases; clinical profile and antibiotic sensitivity of S. Typhi and Paratyphi
27407999	2007	Surveillance	Med J Armed Forces India	Drug susceptibility of 45 enteric fever isolates, including re-emerging chloramphenicol sensitivity
8354556	1993	Epidemiological survey	Indian J Pathol Microbiol	280 S. Typhi strains; multidrug-resistant strains remained sensitive to aminoglycosides, including amikacin
16410091	2006	Case series	J Pediatr Surg	Four children with splenic abscess managed by percutaneous drainage and antibiotics
30724049	2018	Microbiological survey	Pak J Biol Sci	Isolation and identification of S. Paratyphi from enteric fever patients in Quetta
14596347	2003	Epidemiological survey	New Microbiol	Occurrence of S. Typhi and Paratyphi in Jordan, 1988–2000

None of these studies provides controlled evidence of amikacin efficacy in paratyphoid fever.

Singapore Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
SIN11944P	ILDONG AMIKACIN INJECTION 500 mg/2 ml	Injection	Not stated in the available records
SIN15908P	AKACIN INJECTION 500MG/2ML	Injection, solution	Not stated in the available records

Safety Considerations

Disease-related cautions (knowledge-graph based, not label text): Kidney disease, pyoureter, hypercalcaemia, nephrocalcinosis, phosphorus metabolism disorders, central nervous system vertigo, myasthenia gravis (including adult-onset), neuromuscular junction disease, parkinsonian disorders and Parkinson disease.
Drug Interactions (100 interactions recorded; examples):
- Major: Magnesium sulfate, Mannitol
- Moderate: Amphotericin B (including lipid and liposomal forms), Kanamycin, Neomycin, Acetylsalicylic acid, Exenatide, mesalazine-type agents (Balsalazide, Mesalazine, Olsalazine), and proton pump inhibitors (Omeprazole, Esomeprazole, Lansoprazole, Dexlansoprazole, Pantoprazole, Rabeprazole)

Please refer to the package insert for label warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction rests only on model scoring and in vitro or epidemiological data. There are no clinical trials, and no study shows clinical efficacy of amikacin in paratyphoid fever. Aminoglycosides penetrate cells poorly, effective first-line alternatives exist, and amikacin carries notable nephrotoxicity, ototoxicity and neuromuscular risks, so the unmet need and benefit–risk case are weak.

To proceed, the following is needed:

Package insert warnings and contraindications from the HSA (currently missing and blocking safety screening)
Mechanism of action data
Clinical or at least robust in vivo evidence of amikacin efficacy against Salmonella Paratyphi, including intracellular activity
Comparison with standard therapy (fluoroquinolones, azithromycin, third-generation cephalosporins), particularly in multidrug-resistant cases
Approved indication text for the two Singapore licences, to confirm the on-label scope

Other predictions in this evaluation (all Hold): typhoid fever and salmonellosis (L4; in vitro and case-level evidence only, with one small comparison showing a 36.4% clinical effective rate for amikacin versus 100% for ofloxacin in typhoid fever), meningococcemia (L4; no direct amikacin evidence), and diffuse scleroderma, punctate epithelial keratoconjunctivitis, epiglottitis, congenital analbuminemia, polyclonal hyperviscosity syndrome and hyperamylasemia (L5; model prediction only, several likely knowledge-graph artifacts).

Disclaimer

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