Microbial Keratitis: Resistance Patterns and Therapeutic Limitations in the Modern Era

Abstract

Microbial keratitis (MK) is a major global cause of corneal blindness. Although management strategies are well-established, the rising burden of antimicrobial resistance (AMR) is limiting the efficacy of conventional therapies. This review explores emerging resistance trends among bacterial and fungal pathogens. The review further examines the practical challenges clinicians face in treating MK, particularly in resource-limited settings.

Introduction

MK is a vision-threatening corneal infection caused predominantly by bacteria and fungi. It represents a significant burden in both high-income countries (HICs) and low- and middle-income countries (LMICs). While early intervention can prevent sight loss, management is increasingly complicated by antimicrobial resistance. The growing ineffectiveness of first-line therapies, combined with delayed diagnosis and limited drug accessibility, is narrowing the therapeutic window, and heightening the risk of permanent visual disability (Ung et al., 2019; Ting et al., 2021).

Epidemiology and Aetiology

The causative organisms of MK vary geographically. In HICs, Pseudomonas aeruginosa and Staphylococcus aureus are the most common bacterial isolates, particularly among contact lens wearers (Stapleton et al., 2008). In LMICs, filamentous fungi such as Fusarium and Aspergillus predominate, often following corneal trauma (Gopinathan et al., 2009). Despite these variations, resistance is emerging across all major pathogen groups and is increasingly recognised as a global concern.

Bacterial Resistance Patterns

Resistance among bacterial keratitis isolates is rising, particularly against fluoroquinolones—agents often used empirically. Data from India shows ciprofloxacin resistance in over 15% of P. aeruginosa and 30% of S. aureus isolates, with methicillin-resistant S. aureus (MRSA) now commonly encountered (Lalitha et al., 2007; Schaefer et al., 2001). In the UK, surveillance reports have noted reduced susceptibility of S. aureus to key drugs in empirical protocols such as chloramphenicol and moxifloxacin, (BSAC, 2022).

P. aeruginosa presents unique challenges due to intrinsic resistance mechanisms. Efflux pumps, reduced outer membrane permeability, and biofilm formation confer resistance to multiple drug classes, making treatment particularly difficult in monotherapy or when culture results are delayed (Willcox, 2011).

Fungal Resistance and Therapeutic Failure

Despite being less frequently reported, antifungal resistance is equally as concerning. Natamycin remains the standard treatment for filamentous fungal keratitis, but resistance has been documented, especially in regions where agricultural fungicide use is high (Mohd-Tahir et al., 2012). Voriconazole, a broad-spectrum azole, has shown limited clinical efficacy against Fusarium species. In a major randomised trial, voriconazole was associated with worse outcomes compared to natamycin in terms of both healing and visual acuity (Prajna et al., 2010).

Further complicating management, antifungal susceptibility testing is rarely available in routine practice, and alternatives such as amphotericin B are limited by poor ocular penetration and toxicity (Lusby et al., 2020).

Treatment Delivery Challenges

MK treatment is frequently initiated empirically due to diagnostic delays. Culture positivity rates range from 50–70%, and results often take several days, even in well-equipped settings (Ting et al., 2021). This forces clinicians to rely on broad-spectrum coverage, which may be ineffective in resistant cases.

In moderate to severe bacterial keratitis, fortified antibiotics such as vancomycin and ceftazidime are often required (AAO, 2018). These are not commercially available and must be prepared in hospital pharmacies. Frequent dosing—often every 30 minutes initially—makes adherence difficult, especially for elderly patients or those without carers.

Topical antifungals present additional limitations. Treatment is prolonged, drug penetration is poor, and availability is inconsistent. Natamycin remains inaccessible in many LMICs despite being the most effective agent against filamentous fungi (Whitcher et al., 2001). Systemic antifungal therapy adds little benefit in most cases due to low intraocular bioavailability and systemic side effects (Thomas, 2003).

Addressing the Resistance Challenge

Improving diagnostic capability is essential especially when considering conventional culture methods are slow and often inconclusive. Molecular diagnostics such as PCR and next-generation sequencing thereby offer faster and more accurate pathogen identification, though their high cost and limited availability restrict widespread use (Bagga et al., 2023).

Resistance surveillance must also improve. Many empirical regimens rely on outdated or non-ophthalmic data, leading to inappropriate first-line prescribing. Regular reporting of resistance patterns in ocular isolates would allow for localised, evidence-based updates to treatment guidelines (BSAC, 2022).

Novel therapeutics are needed to circumvent current resistance mechanisms. Antimicrobial peptides, bacteriophage therapy, and nanocarrier-based drug delivery systems have all shown early promise (Zegans et al., 2020). While these remain experimental, they represent future options for recalcitrant infections where conventional therapies are failing.

Global access to effective treatments remains a critical issue in therapeutic limitations. Ensuring the availability of essential drugs in endemic regions should be prioritised through regulatory support and public-private partnerships (Whitcher et al., 2001).

Finally, prevention remains key. Public education on contact lens hygiene, agricultural eye protection, and prompt medical attention can further reduce the incidence and severity of MK (WHO, 2015).

Conclusion

Antimicrobial resistance in microbial keratitis is no longer a distant threat -it is a present and growing challenge that is complicating empirical management and contributing to poorer outcomes worldwide. Resistance in P. aeruginosa, MRSA, and filamentous fungi is narrowing therapeutic options paired with persistent limitations in clinical diagnostics and delivery. For the future, a combined approach focusing on resistance surveillance, drug innovation, and global access to treatment is urgently needed. Without intervention, the burden of MK will continue to grow, even in the face of modern ophthalmic care.

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