Amikacin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Amikacin: From Bacterial Infections to Paratyphoid Fever
One-Sentence Summary
Amikacin is an aminoglycoside antibiotic originally used for serious Gram-negative and other bacterial infections, such as bacterial pneumonia, Pseudomonas aeruginosa infection and bacterial meningitis. The TxGNN model predicts it may be effective for paratyphoid fever, but the evidence is thin: no clinical trials are registered and the 8 publications retrieved are almost entirely epidemiology, antibiogram data and case reports.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Bacterial pneumonia, Pseudomonas aeruginosa infection, bacterial meningitis and other bacterial infections (approved indication text is not available in the India registrations) |
| Predicted New Indication | Paratyphoid fever |
| TxGNN Prediction Score | 0.9982 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled data. Based on known information, amikacin is an aminoglycoside that inhibits the bacterial 30S ribosomal subunit and has activity against Gram-negative bacteria. Its efficacy in Gram-negative infections is established, and Salmonella Paratyphi is a Gram-negative Enterobacterales pathogen, so activity is biologically plausible.
There are important limits. Salmonella is an intracellular pathogen, and aminoglycosides penetrate cells poorly, which restricts their usefulness in enteric fever. The retrieved literature does not show controlled evidence of amikacin efficacy in paratyphoid fever. The high TxGNN score mostly reflects similarity to other antibacterial uses.
The closely related prediction of typhoid fever (rank 4) has somewhat stronger support. An in vitro study (PMID 19554971) found 464 S. Typhi isolates sensitive to amikacin and gentamicin. Amikacin has also appeared in case reports as part of combination regimens. However, a small clinical study (PMID 2598731) reported a clinical effective rate of only 36.4% with amikacin (11 patients) versus 100% with ofloxacin. Amikacin might at most be a salvage option for extensively drug-resistant isolates, which would need clinical validation.
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 | Child with leukaemia and acalculous cholecystitis due to S. Paratyphi B treated successfully with cefepime, amikacin and granulocyte support |
| 18383953 | 2007 | Cohort | Journal of the Indian Medical Association | Prospective study of 145 children with enteric fever, covering clinical profile and antibiotic sensitivity of S. Typhi and Paratyphi |
| 27407999 | 2007 | Observational | Medical Journal, Armed Forces India | Susceptibility of 45 enteric fever isolates in northern India; chloramphenicol sensitivity re-emerging |
| 2516600 | 1989 | Clinical report | Mikrobiyoloji Bulteni | Treatment and antibiogram results in 48 patients with resistant paratyphi B infection |
| 16410091 | 2006 | Case series | Journal of Pediatric Surgery | Four children with splenic abscess managed by percutaneous drainage plus antibiotics |
| 8354556 | 1993 | Surveillance | Indian Journal of Pathology & Microbiology | Multidrug-resistant S. Typhi in Ludhiana; resistant strains remained sensitive to aminoglycosides and ciprofloxacin |
| 14596347 | 2003 | Epidemiology | The New Microbiologica | Occurrence of S. Typhi and Paratyphi in Jordan |
| 30724049 | 2018 | Surveillance | Pakistan Journal of Biological Sciences | Isolation and identification of S. Paratyphi from enteric fever patients in Quetta |
| 26905550 | 2014 | Surveillance | JNMA | Blood culture isolates and antibiogram in a teaching hospital |
India Market Information
Approved indication text is not available for these registrations.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| 20010 | Ambix 500mg Injection | Vial of 1 injection | Biobrick Pharma |
| 25443 | Amitop 500mg Injection | Vial of 2 ml injection | Veliko Pharmacls |
| 25160 | Amicid 250mg Injection | Vial of 1 injection | Indus Pharma Pvt Ltd |
| 149071 | Mikadef 500mg Injection | Vial of 2 ml injection | Clabert Lifesciences Pvt Ltd |
| 148230 | Mikmor 100mg Injection | Vial of 1 injection | Moral Pharmaceuticals |
All 20 registrations are valid single-ingredient injectable products.
Safety Considerations
- Disease-level cautions (from the knowledge graph, not label text): the following conditions are linked to amikacin as contraindications or cautions: kidney disease, pyoureter, hypercalcemia, nephrocalcinosis, phosphorus metabolism disease, central nervous system origin vertigo, myasthenia gravis (including adult-onset), neuromuscular junction disease, and parkinsonian disorders including Parkinson disease.
- Drug Interactions: 212 interactions were identified. The major-level interactions in the data compiled for this report are magnesium sulfate and mannitol. Moderate interactions include other aminoglycosides (kanamycin, neomycin), amphotericin B formulations, acetylsalicylic acid, mesalazine and related drugs, and several proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole).
Please refer to the package insert for key warnings and contraindications, as label text was not available.
Conclusion and Next Steps
Decision: Hold
Rationale: The paratyphoid fever prediction has no clinical trials and only epidemiology, surveillance and case-level literature, with no controlled evidence of amikacin efficacy. Poor intracellular penetration of aminoglycosides, together with their nephrotoxicity and ototoxicity risks, argues against advancing this indication, and established alternatives exist for enteric fever.
To proceed, the following is needed:
- Package insert warnings and contraindications (a blocking gap for safety screening)
- Detailed mechanism of action data
- Controlled or comparative clinical data on amikacin in enteric fever, ideally focused on drug-resistant isolates
- Review of the related typhoid fever prediction (rank 4, evidence L3), which is a stronger candidate for a research question than paratyphoid fever alone
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.