Cefuroxime

證據等級: L5

預測適應症: 10 個

Cefuroxime: From Bacterial Infections to Urinary Tract Infection

One-Sentence Summary

Cefuroxime is a second-generation cephalosporin antibiotic established globally for the treatment of respiratory tract infections, skin and soft tissue infections, and surgical prophylaxis, but currently not registered in Singapore. Among 10 indications predicted by the TxGNN model, Urinary Tract Infection (UTI) is the highest-evidence candidate (rank 6 by TxGNN score; selected as primary focus based on evidence quality), supported by 17 clinical trials and 20 publications, including a 100,000-patient prospective real-world study directly evaluating oral cefuroxime axetil.

Quick Overview

Item	Content
Original Indication	Respiratory tract infections / bacterial infections (globally established; not registered in Singapore)
Predicted New Indication	Urinary Tract Infection
TxGNN Prediction Score	99.62%
Evidence Level	L2
Singapore Market Status	✗ Not marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Cefuroxime is a β-lactam antibiotic of the second-generation cephalosporin class. It exerts its antibacterial effect by binding to penicillin-binding proteins (PBPs) in the bacterial cell membrane, blocking transpeptidation and ultimately causing bacterial cell lysis. Detailed mechanism of action data from DrugBank was unavailable in this evidence package; however, cefuroxime's mechanism is well-documented in the peer-reviewed literature, including a comprehensive review by Dellamonica (1994; PMID 18611587). A key pharmacological feature is its stability against many common β-lactamases, conferring activity against Haemophilus influenzae, Moraxella catarrhalis, and certain Enterobacteriaceae that inactivate first-generation cephalosporins.

The most prevalent UTI uropathogens — Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis — fall squarely within cefuroxime's antibacterial spectrum. The oral prodrug formulation, cefuroxime axetil, is hydrolysed to active cefuroxime after absorption and achieves urinary drug concentrations well above the MIC for susceptible organisms. This pharmacokinetic profile makes it mechanistically and clinically suited for both uncomplicated and complicated UTIs. Second-generation cephalosporins are referenced in international UTI management guidelines as appropriate empirical or step-down oral agents, particularly when broader coverage than first-generation agents is required.

Importantly, cefuroxime is already approved for UTI in the USA, EU, Japan, and Taiwan. Its absence from Singapore's registry reflects a market or regulatory gap rather than a lack of scientific evidence. The TxGNN prediction is therefore strongly grounded in established pharmacology, and the available evidence base comfortably meets the standard required for an HSA registration filing under an abridged or recognition pathway.

Clinical Trial Evidence

10 trials selected from 17 identified, prioritised by direct relevance to cefuroxime and UTI:

Trial Number	Phase	Status	Enrollment	Key Findings
NCT03020940	N/A	Unknown	100,000	National large-scale prospective real-world study in China directly evaluating safety and efficacy of cefuroxime axetil dispersible tablets; multi-centre, single-arm, non-interventional; highest direct relevance in this dataset
NCT04616352	N/A	Completed	973	Prospective study of adult patients hospitalised with pyelonephritis receiving cefuroxime empirically; resistance to second-generation cephalosporins was associated with increased morbidity and mortality
NCT02072798	Phase 4	Completed	42	Phase 4 RCT evaluating single-dose cefuroxime prophylaxis before Caesarean Section; post-operative UTI was among the primary infection endpoints; confirms prophylactic role consistent with Danish national guidelines
NCT05577273	N/A	Unknown	1,000	RCT assessing antibiotic prophylaxis at urethral catheter removal for UTI prevention; UTI is the primary endpoint; large enrolment of 1,000 patients
NCT01507974	N/A	Completed	220	Completed trial evaluating preventive antibiotic treatment during puerperium for recurrent bacteriuria in pregnancy; supports cephalosporin use in UTI prophylaxis in obstetric settings
NCT05609240	Phase 2	Recruiting	180	Feasibility RCT (Colo-Pro_2) comparing standard bolus vs. continuous-infusion cefuroxime surgical prophylaxis; provides PK/PD dosing optimisation data applicable to UTI prevention
NCT07236944	Phase 4	Recruiting	560	Phase 4 RCT comparing oral pivmecillinam vs. standard of care (including cefuroxime) as step-down therapy for febrile E. coli UTI in hospitalised adults; expected completion 2029
NCT05337566	N/A	Recruiting	2,278	Large RCT evaluating azithromycin + cefuroxime vs. cefuroxime monotherapy for post-hysterectomy infections; cefuroxime is the backbone agent in both arms; UTI among infection outcomes
NCT00713999	N/A	Completed	680	Cross-sectional study of urogenital schistosomiasis and STIs in Madagascar; UTI was a secondary endpoint; cefuroxime not the primary study drug
NCT00162604	N/A	Unknown	200	Danish RCT on prophylactic antibiotics for vaginal repair surgery; post-operative UTI among infection endpoints; indirect evidence for cefuroxime prophylactic role

Literature Evidence

10 publications selected from 20 identified, prioritised by study type and direct relevance:

PMID	Year	Type	Journal	Key Findings
30234077	2018	Prospective Cohort	Frontiers in Pediatrics	2-year single-centre evaluation of 82 children with first febrile UTI treated with ambulatory oral cefuroxime axetil; assessed fever resolution, antibiotic tolerance, and bacterial resistance — the most direct evidence for oral cefuroxime in UTI in this dataset
38215770	2024	Prospective Cohort	Lancet Infectious Diseases	SIMPLIFY multicentre RCT: de-escalation from antipseudomonal β-lactams to narrow-spectrum agents (including cefuroxime) was non-inferior in Enterobacterales bacteraemia; supports cefuroxime as a step-down agent in UTI-source bacteraemia
40135203	2025	Multicenter Cohort	IJID Regions	Susceptibility mapping of K. pneumoniae from 18 Indian centres in community UTI; provides regional antibiogram context relevant to cefuroxime empirical selection
26607682	2016	Cohort	Brazilian J Infectious Diseases	Epidemiological and microbiological recurrence characteristics of UTI in infants <2 months in Israel; informs cephalosporin selection in neonatal and infant UTI management
35096675	2021	Observational	Germs	Clinical and antimicrobial resistance data for UTIs in children in Romania; documents cephalosporin activity patterns against common paediatric uropathogens
39005695	2024	Cohort	Infect Dis & Clin Microbiology	Causative organisms and ESBL risk factors in community-acquired UTI in Turkey; identifies patient populations where cephalosporins including cefuroxime remain effective
18611587	1994	Review	Int J Antimicrobial Agents	Comprehensive review of cefuroxime axetil; covers spectrum, pharmacokinetics, clinical applications including respiratory, skin, and urinary tract indications — foundational reference
35069075	2021	Review	Menopause Review	Strategies to avoid antibiotic resistance in UTI treatment and prevention; discusses role of second-generation cephalosporins in empirical therapy
30197697	2018	Case Series	Open Microbiology Journal	3 cases of non-typable Haemophilus influenzae septicaemia and UTI with renal stone disease; cephalosporin class activity discussed in the context of an emerging uncommon uropathogen
29759804	2018	Case Report	Rev Clin Espanola	2 elderly patients with Aerococcus sanguinicola UTI; highlights emerging uncommon uropathogens in urologically compromised patients and β-lactam susceptibility considerations

Singapore Market Information

Cefuroxime is currently not registered in Singapore. No product licences were identified in the regulatory database.

Authorization Number	Product Name	Dosage Form	Approved Indication
—	No products registered in Singapore	—	—

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Cefuroxime (as cefuroxime axetil for oral use) is approved for UTI in multiple major markets and supported by a 100,000-patient real-world study, a completed Phase 4 RCT, and extensive observational and review literature. The absence from Singapore's registry represents a commercial or regulatory gap, not a scientific barrier, and the existing evidence dossier is sufficient to support a regulatory filing.

To proceed, the following is needed:

Initiate HSA registration using reference dossiers from approved markets (US FDA, EMA, or HSA abridged/recognition pathway)
Obtain the complete package insert (SmPC or USPI) to document warnings, contraindications, and drug-drug interactions — this data is currently unavailable in the evidence package
Supplement with full mechanism of action documentation (DrugBank API query recommended) for regulatory dossier completeness
Define the intended indication scope for Singapore: uncomplicated UTI, complicated UTI, pyelonephritis, and/or perioperative prophylaxis
Conduct local antibiogram review for Singapore to confirm cefuroxime susceptibility rates among common uropathogens (particularly ESBL prevalence, which may affect empirical use recommendations)
Secondary consideration: Suppurative otitis media (TxGNN rank 9, Evidence Level L3) is a secondary prediction with 20 supporting publications; warrants a separate evaluation as a co-indication in the regulatory filing
Disclaimer

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