Combined intrastromal injection of amphotericin B and topical fluconazole in the treatment of resistant cases of keratomycosis: a retrospective study

Nada, Waled M; Aswad, Mahmoud A Al; El-Haig, Wael M

doi:10.2147/opth.s135112

Cited by 21 publications

(11 citation statements)

References 8 publications

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“…The healing rate of 90% with ISAMB in the present study is also comparable to that of Nada et al's study (83%). 7 However, the need for administering repeat injections was higher in this group. This could be due to delayed healing, as depicted by slow resolution of epithelial defect, stromal infiltrates and hypopyon, all of which could have ultimately resulted in exaggerated inflammation and therefore larger final scar size, and significantly higher propensity to develop deep vascularization with ISAMB.…”

Section: Discussionmentioning

confidence: 70%

“… 6 Similarly, intrastromal Amphotericin-B (ISAMB) has also been employed successfully for targeted drug delivery. 7 In an experimental study in rabbit eyes by Mimouni et al, intrastromal natamycin (ISNTM) was employed successfully for treatment of Fusarium keratitis. 8 While many studies have individually described the utility of these drugs for intrastromal injections in recalcitrant fungal keratitis, there is a relative paucity of peer-reviewed literature prospectively comparing the safety and efficacy of these drugs.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Safety and Efficacy of Intrastromal Injections of Voriconazole, Amphotericin B and Natamycin in Cases of Recalcitrant Fungal Keratitis: A Randomized Controlled Trial

Saluja¹,

Sharma²,

Agarwal³

et al. 2021

OPTH

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Objective To compare the safety and efficacy of intrastromal voriconazole (IS-VCZ), amphotericin B (IS-AMB) and natamycin (IS-NTM) as an adjunct to topical natamycin (NTM) in cases of recalcitrant fungal keratitis. Design Prospective randomized trial. Setting Tertiary eye centre. Participants Sixty eyes of 60 patients with microbiologically proven recalcitrant fungal keratitis (ulcer size >2 mm, depth >50% of stroma, and not responding to topical NTM therapy for two weeks) were recruited. Methods patients were randomized into three groups of 20 eyes, each receiving ISVCZ 50ug/0.1 mL, ISAMB, 5ug/0.1 mL and ISNTM 10ug/0.1 mL (prepared aseptically in ocular pharmacology). The patients in all three groups continued topical NTM 5% every four hours until the ulcer healed. Primary outcome measure was time taken till complete clinical resolution of infection, and secondary outcome measure was best corrected visual acuity (BCVA) at six months. Results All three groups had comparable baseline parameters. The mean duration of healing was significantly better (p=0.02) in the ISNTM group (34±5.2 days) as compared to the ISVCZ group (36.1±4.8 days) and the ISAMB group (39.2±7.2 days). About 95%, 90% and 95% patients healed successfully in the ISVCZ, ISAMB and ISNTM groups, respectively. In terms of healing, deep vascularization was significantly greater in the ISAMB group (55%, p=0.02) when compared to the ISVCZ and ISNTM groups (31% and 26%, respectively). There were fewer repeat injections in the ISNTM group (7/20 vs 8/20 and 9/20 in the ISVCZ and ISNTM groups, respectively). Conclusion Intrastromal injections are a safe and effective adjunct to conventional therapy in the management of recalcitrant fungal keratitis. ISNTM had a similar visual outcome with faster healing while ISAMB had a higher rate of deep vascularization after healing.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Comparison of Safety and Efficacy of Intrastromal Injections of Voriconazole, Amphotericin B and Natamycin in Cases of Recalcitrant Fungal Keratitis: A Randomized Controlled Trial

Saluja¹,

Sharma²,

Agarwal³

et al. 2021

OPTH

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“…26 Alternative administration routes, such as inhalation for VRZ, 27,28 ITZ, 29 and 5FC, 30 have given encouraging results. Eye drops, 31 intrastromal injections, 32–34 and ocular inserts 35 have also been shown to yield satisfactory outcomes for fungal keratitis. New innovative galenic formulations, such as oral formulations of AmB for systemic use (iCo-019, encochleated AmB) 36,37 and liposomal VRZ, 38 are being studied and their impact on TDM must be evaluated.…”

Section: General Considerationsmentioning

confidence: 99%

Antifungal Drugs TDM: Trends and Update

Kably

Launay

Derobertmasure

et al. 2022

Therapeutic Drug Monitoring

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The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM. Methods:We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-druginteraction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure.Results: More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available.Conclusions: TDM seems to be crucial for curative and/or longterm maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.

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“…Subconjunctival injection, the other route, which attempts to increase drug compliance and concentration, is not favoured due to the resulting conjunctival granuloma formation [102], necrosis and scleritis [103]. Successful use of subconjunctival amphotericin B without any complications in combination with topical amphotericin B and other standard anti-fungal agents has also been reported [104,105]. In an attempt to increase the ocular penetration of amphotericin B, a recent experimental study [106] evaluated the use of a liposomal amphotericin B microneedle ocular patch designed in a contact lens model done ex vivo and in vivo in rabbit models showing with promising results.…”

Section: Amphotericin Bmentioning

confidence: 99%

Recent Perspectives in the Management of Fungal Keratitis

Raj

Vanathi

Ahmed

et al. 2021

JoF

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Mycotic keratitis is common in warm, humid regions with a varying profile of pathogenic fungi according to geographical origin, socioeconomic status, and climatic condition. Clinical diagnosis can be challenging in difficult cases and those refractory to treatment. Fungal hyphae on microscopic examination and culture isolation have been the gold standard in the laboratory diagnosis of fungal keratitis. A culture isolate of the aetiological fungus is essential to perform antifungal susceptibility testing. As the culture isolation of fungi is time-consuming, causing delays in the initiation of treatment, newer investigative modalities such as in vivo confocal microscopy and molecular diagnostic methods have recently gained popularity. Molecular diagnostic techniques now help to obtain a rapid diagnosis of fungal keratitis. Genomic approaches are based on detecting amplicons of ribosomal RNA genes, with internal transcribed spacers being increasingly adopted. Metagenomic deep sequencing allows for rapid and accurate diagnosis without the need to wait for the fungus to grow. This is also helpful in identifying new emerging strains of fungi causing mycotic keratitis. A custom-tear proteomic approach will probably play an important diagnostic role in future in the management of mycotic keratitis. Positive repeat cultures are being suggested as an important gauge indicative of a poor prognosis. Positive repeat fungal cultures help to modify a treatment regimen by increasing its frequency, providing the addition of another topical and oral antifungal agent along with close follow-up for perforation and identifying need for early therapeutic keratoplasty. The role of collagen crosslinking in the treatment of fungal keratitis is not convincingly established. Rapid detection by multiplex PCR and antifungal susceptibility testing of the pathogenic fungi, adopted into a routine management protocol of fungal keratitis, will help to improve treatment outcome. Early therapy is essential in minimizing damage to the corneal tissue, thereby providing a better outcome. The role of conventional therapy with polyenes, systemic and targeted therapy of antifungal agents, newer azoles and echinocandins in fungal keratitis has been widely studied in recent times. Combination therapy can be more efficacious in comparison to monotherapy. Given the diversity of fungal aetiology, the emergence of new corneal pathogenic fungi with varying drug susceptibilities, increasing the drug resistance to antifungal agents in some genera and species, it is perhaps time to adopt recent molecular methods for precise identification and incorporate antifungal susceptibility testing as a routine.

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Combined intrastromal injection of amphotericin B and topical fluconazole in the treatment of resistant cases of keratomycosis: a retrospective study

Cited by 21 publications

References 8 publications

Comparison of Safety and Efficacy of Intrastromal Injections of Voriconazole, Amphotericin B and Natamycin in Cases of Recalcitrant Fungal Keratitis: A Randomized Controlled Trial

Comparison of Safety and Efficacy of Intrastromal Injections of Voriconazole, Amphotericin B and Natamycin in Cases of Recalcitrant Fungal Keratitis: A Randomized Controlled Trial

Antifungal Drugs TDM: Trends and Update

Recent Perspectives in the Management of Fungal Keratitis

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