Amikacin

證據等級: L5

預測適應症: 10 個

Amikacin: From Serious Bacterial Infections to Paratyphoid Fever

One-Sentence Summary

Amikacin is a broad-spectrum aminoglycoside antibiotic originally used to treat serious Gram-negative bacterial infections, particularly in multidrug-resistant (MDR) settings. The TxGNN model predicts it may be effective for Paratyphoid Fever, supported by its established in vitro activity against Salmonella paratyphi. Currently no registered clinical trials and 12 publications (predominantly case reports and epidemiological studies) support this direction.

Quick Overview

Item	Content
Original Indication	Serious Gram-negative bacterial infections (aminoglycoside antibiotic; not currently registered in India)
Predicted New Indication	Paratyphoid Fever
TxGNN Prediction Score	99.82%
Evidence Level	L4
India Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Amikacin is a semi-synthetic aminoglycoside antibiotic that exerts its bactericidal effect by irreversibly binding to the 30S ribosomal subunit of susceptible bacteria, thereby disrupting mRNA translation and causing misreading of the genetic code. This mechanism confers broad activity against aerobic Gram-negative bacilli, including members of the Enterobacteriaceae family. Detailed MOA data from the regulatory package insert is currently unavailable for this market; the mechanism described here is based on established pharmacological knowledge of the aminoglycoside class.

Salmonella paratyphi — the causative agent of paratyphoid fever — is a Gram-negative facultative intracellular rod that falls squarely within Amikacin’s spectrum of activity. In vitro susceptibility studies and antibiogram surveys consistently demonstrate sensitivity of S. paratyphi strains to Amikacin, particularly in contexts where first-line agents (fluoroquinolones, third-generation cephalosporins, or chloramphenicol) have failed due to resistance. Multiple clinical case reports document Amikacin being deployed as a rescue or combination antibiotic in MDR enteric fever scenarios originating from the Indian subcontinent and surrounding regions.

The key biological limitation to this prediction is the intracellular niche of Salmonella during systemic infection: aminoglycosides penetrate poorly into eukaryotic cells, reducing efficacy against the intracellular reservoir of the pathogen. Consequently, Amikacin is not a first-line treatment for paratyphoid fever, but represents a clinically reasonable option in MDR or fluoroquinolone-resistant settings. The TxGNN knowledge-graph model’s prediction is therefore mechanistically grounded — the link is real, but the clinical utility is niche and context-dependent.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
18383953	2007	Prospective Cohort	Journal of the Indian Medical Association	Prospective study of 145 blood culture-positive enteric fever cases in children; documents antibiotic sensitivity patterns for S. typhi and S. paratyphi, including aminoglycoside susceptibility.
2516600	1989	Clinical Treatment Study	Mikrobiyoloji Bulteni	Treatment outcomes in 48 children with Salmonella paratyphi B infection resistant to classical antibiotics; aminoglycoside regimens evaluated as alternatives.
10505326	1999	Case Report	Pediatric Hematology and Oncology	Acalculous cholecystitis caused by S. paratyphi B in a child with leukemia; successful treatment with cefepime plus Amikacin and granulocyte colony-stimulating factor.
9459410	1997	Case Report	The Journal of Infection	Newborn meningitis due to quinolone-resistant S. paratyphi B; illustrates the need for alternative agents including aminoglycosides when fluoroquinolones fail.
17337835	2007	Case Series	Indian Journal of Pediatrics	Paratyphoid sepsis in a neonate; blood culture grew multidrug-susceptible S. paratyphi A; documents clinical profile and antibiotic management.
30724049	2018	Epidemiological/Microbiological	Pakistan Journal of Biological Sciences	Isolation and identification of Salmonella paratyphi in Quetta City; reports increasing incidence and antimicrobial susceptibility patterns including aminoglycosides.
26905550	2014	Retrospective Antibiogram	JNMA – Journal of the Nepal Medical Association	Blood culture isolate antibiogram from a teaching hospital; Amikacin susceptibility data included for Salmonella spp.
27407999	2007	Antibiogram Study	Medical Journal, Armed Forces India	In vitro susceptibility of S. typhi and S. paratyphi A from northern India; all strains sensitive to aminoglycosides.
14596347	2003	Epidemiological Survey	The New Microbiologica	Occurrence of S. typhi and S. paratyphi in Jordan 1988–2000; background epidemiological context for treatment relevance.
16410091	2006	Case Series	Journal of Pediatric Surgery	Splenic abscess in pediatric patients treated with needle aspiration and antibiotics; context includes enteric fever complications managed with combination regimens.

India Market Information

Amikacin (DB00479) is not currently registered or marketed in India according to the regulatory data in this Evidence Pack. No license records, dosage form approvals, or approved indication texts are available.

Note: Amikacin is widely available in other markets (e.g., intravenous injection formulations are approved in the US, EU, and numerous Asian countries) for serious Gram-negative bacterial infections. The absence from this dataset may reflect a data gap rather than true unavailability in the Indian market. Independent verification via CDSCO databases is recommended.

Safety Considerations

Drug Interactions (212 interactions identified; key interactions listed below):

Severity	Interacting Drug	Clinical Significance
Major	Magnesium sulfate	Risk of enhanced neuromuscular blockade and respiratory depression; avoid concurrent use or monitor closely
Major	Mannitol	Combined nephrotoxicity risk; concurrent use may increase renal impairment
Moderate	Amphotericin B (all formulations)	Additive nephrotoxicity; monitor renal function closely if co-administration is unavoidable
Moderate	Kanamycin / Neomycin	Additive ototoxicity and nephrotoxicity (aminoglycoside-on-aminoglycoside); avoid combination
Moderate	Acetylsalicylic acid	May mask aminoglycoside-induced ototoxicity; monitor hearing
Moderate	PPIs (Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole, Dexlansoprazole, Rabeprazole)	Pharmacokinetic interaction; clinical significance varies, monitor response
Moderate	5-ASA agents (Mesalazine, Olsalazine, Balsalazide)	Potential additive nephrotoxicity in patients with inflammatory bowel disease
Moderate	Exenatide	Altered drug absorption/transit; monitor glycaemic control and antibiotic efficacy

Key clinical note: Amikacin belongs to the aminoglycoside class, which carries well-established risks of nephrotoxicity and ototoxicity (both auditory and vestibular). These require therapeutic drug monitoring (TDM), renal function tracking, and audiometric surveillance, particularly with prolonged use or in renally impaired patients.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The mechanistic link between Amikacin and Salmonella paratyphi is biologically valid — aminoglycosides bind the 30S ribosomal subunit and S. paratyphi consistently shows in vitro susceptibility — making this a plausible rescue therapy for fluoroquinolone- or multi-drug-resistant paratyphoid fever. However, the evidence base consists entirely of case reports, antibiogram surveys, and epidemiological studies (L4), with no registered clinical trials, and the drug is not currently approved in India, which limits immediate clinical translation.

To proceed, the following is needed:

Formal MOA documentation: Retrieve the package insert or DrugBank full record to confirm mechanism of action and class-specific warnings
Regulatory gap assessment: Verify actual CDSCO registration status through the official database, as the current dataset shows zero records which may be incomplete
Resistance landscape review: Commission a contemporary antibiogram survey of S. paratyphi strains in the target geography to confirm that clinically relevant Amikacin susceptibility persists
PK/PD analysis for intracellular pathogens: Evaluate whether liposomal Amikacin formulations or alternative dosing strategies (e.g., once-daily high-dose) could overcome the intracellular penetration limitation
Prospective pilot study design: Given L4 evidence, a small prospective cohort or comparative case series study in MDR-paratyphoid patients (where standard therapy has failed) would be the appropriate next step before any clinical adoption
Safety monitoring plan: Define nephrotoxicity and ototoxicity monitoring protocols (serum creatinine, BUN, trough/peak levels, audiometry) appropriate for the target patient population

⚠️ Disclaimer: This report is for research reference only and does not constitute medical advice. Drug repurposing candidates require clinical validation before application. All content is subject to the YMYL standard: predicted indications must undergo formal clinical evaluation before therapeutic use.

Disclaimer

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