Changing Azole Resistance

Prajna, N Venkatesh; Lalitha, Prajna; Rajaraman, Revathi; Krishnan, Tiruvengada; Raghavan, Anita; Srinivasan, Muthiah; O’Brien, Kieran; Zegans, Michael E.; McLeod, Stephen D.; Acharya, Nisha R.; Keenan, Jeremy D.; Lietman, Thomas M.; Rose‐Nussbaumer, Jennifer

doi:10.1001/jamaophthalmol.2016.0530

Cited by 19 publications

(14 citation statements)

References 11 publications

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“…Another study conducted in Taiwan also highlighted the emerging issue of methicillin resistance, with MRSA accounting for 43% of all Gram-positive IK [ 38 ]. On the other hand, an increase in voriconazole resistance was observed in the Mycotic Ulcer Treatment Trial (MUTT)-I for fungal keratitis, with a 2.1-fold increase in the mean MIC per year after adjustment for causative organism [ 151 ].…”

Section: Antimicrobial Resistance (Amr)mentioning

confidence: 99%

Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance

Ting

Deshmukh

et al. 2021

Eye

270

243

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Corneal opacity is the 5th leading cause of blindness and visual impairment globally, affecting ~6 million of the world population. In addition, it is responsible for 1.5–2.0 million new cases of monocular blindness per year, highlighting an ongoing uncurbed burden on human health. Among all aetiologies such as infection, trauma, inflammation, degeneration and nutritional deficiency, infectious keratitis (IK) represents the leading cause of corneal blindness in both developed and developing countries, with an estimated incidence ranging from 2.5 to 799 per 100,000 population-year. IK can be caused by a wide range of microorganisms, including bacteria, fungi, virus, parasites and polymicrobial infection. Subject to the geographical and temporal variations, bacteria and fungi have been shown to be the most common causative microorganisms for corneal infection. Although viral and Acanthamoeba keratitis are less common, they represent important causes for corneal blindness in the developed countries. Contact lens wear, trauma, ocular surface diseases, lid diseases, and post-ocular surgery have been shown to be the major risk factors for IK. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though its effectiveness is being challenged by the emergence of antimicrobial resistance, including multidrug resistance, in some parts of the world. In this review, we aim to provide an updated review on IK, encompassing the epidemiology, causative microorganisms, major risk factors and the impact of antimicrobial resistance.

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Section: Antimicrobial Resistance (Amr)mentioning

confidence: 99%

Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance

Ting

Deshmukh

et al. 2021

Eye

270

243

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“…In essence, we found an increase in azole resistance of filamentous fungi recovered from baseline corneal cultures during MUTT 1 after controlling for the infectious organism. [ 27 ] This assumes significance because azole antifungals are some of the most common antifungals used in agriculture, which may have promoted increasing resistance among the fungal species. It is of special interest to note that Natamycin is not used in agriculture.…”

Section: Drug Trialsmentioning

confidence: 99%

Fungal keratitis: The Aravind experience

Prajna

Lalitha

Srinivasan

2017

Indian J Ophthalmol

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Research becomes very significant and meaningful when it addresses a significant public health problem of a region. Fungal keratitis is a serious problem affecting the agrarian poor and hence requires attention from public health specialists. The approach to a public health issue should focus not only on treatment but also prevention or at least show a significant thrust to reduce the morbidity of the problem. At our institution, we have developed a special interest in fungal keratitis and tried to study it in a multitude of aspects. As we put the pieces of the puzzle together, we believe that interest will be rekindled among policymakers, clinicians, microbiologists, pharmaceutical industry, and basic scientists to work together to join forces and take up an integrative approach to managing this problem. It is also believed that the article underscores the need and importance of having a focused approach to ensuring a successful career in clinical research.

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“…The Mycotic Ulcer Treatment Trial I (MUTT I) found that topical natamycin was superior to topical voriconazole in the treatment of fungal keratitis . In a prespecified secondary analysis of MUTT I, we found an approximate 2-fold increase in azole resistance per year but found no increase in resistance to natamycin . Natamycin, a polyene antifungal, has broad-spectrum activity against filamentous fungi and is thought to inhibit fungal growth by binding to ergosterol.…”

Section: Introductionmentioning

confidence: 78%

“…Similarly, there is evidence that the use of natamycin as a food preservative can be associated with polyene resistance. Concerns about the contribution of agricultural practices to the development of azole or natamycin resistance in clinical infections are not limited to India, as similar observations have been seen in other parts of the world . Filamentous fungal ulcers are already known to have worse outcomes than bacterial ulcers, with nearly 50% of severe ulcers perforating or requiring therapeutic penetrating keratoplasty despite the use of topical natamycin and voriconazole as well as oral voriconazole.…”

Section: Discussionmentioning

confidence: 96%

Patterns of Antifungal Resistance in Adult Patients With Fungal Keratitis in South India

et al. 2022

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IMPORTANCE Antifungal resistance has been shown to impact treatment success, but research analyzing antifungal resistance is scarce. OBJECTIVE To evaluate changes in antifungal resistance over time. DESIGN, SETTING, AND PARTICIPANTS Ad hoc analysis of 3 randomized clinical trials including consecutive patients 18 years and older presenting with smear-positive fungal ulcers to Aravind Eye Hospitals in Madurai, Coimbatore, Pondicherry, and Tirunelveli in South India who participated in 1 of 3 clinical trials: the Mycotic Ulcer Treatment Trials (MUTT) I (2010 to 2011) or II (2010 to 2015) or the Cross-Linking Assisted Infection Reduction (CLAIR) trial (2016 to 2018). This post hoc analysis was designed in March 2021 and data were analyzed in May and November 2021. INTERVENTIONS Minimum inhibitory concentration (MIC) of natamycin and voriconazole was determined from corneal cultures obtained using standardized methods outlined in the Clinical and Laboratory Standards Institute. MAIN OUTCOMES AND MEASURES The primary outcome of this post hoc analysis was MIC of natamycin and voriconazole. RESULTS A total of 890 fungal isolates were obtained from 651 patients (mean [SD] age, 49.6 [13.0]; 191 [43.3%] female) from 2010 to 2018. MICs were available for 522 samples in 446 patients.Fungal isolates overall demonstrated a 1.02-fold increase per year in voriconazole resistance as measured by MICs (95% CI, 1.00-1.04; P = .06). In subgroup analyses, Fusarium species demonstrated a 1.04-fold increase in voriconazole resistance per year (95% CI, 1.00-1.06; P = .01). Fungal isolates showed a 1.06-fold increase in natamycin resistance per year overall (95% CI, 1.03-1.09; P < .001). Fusarium species had a 1.06-fold increase in natamycin resistance (95% CI, 1.05-1.08; P < .001), Aspergillus had a 1.09-fold increase in resistance (95% CI, 1.05-1.15; P < .001), and other filamentous fungi had a 1.07-fold increase in resistance to natamycin per year (95% CI, 1.04-1.10; P < .001). CONCLUSIONS AND RELEVANCEThis post hoc analysis suggests that susceptibility to both natamycin and voriconazole may be decreasing over the last decade in South India. While a trend of increasing resistance could impact treatment of mycoses in general and infectious fungal keratitis in particular, further study is needed to confirm these findings and determine their generalizability to other regions of the world.

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Changing Azole Resistance

Cited by 19 publications

References 11 publications

Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance

Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance

Fungal keratitis: The Aravind experience

Patterns of Antifungal Resistance in Adult Patients With Fungal Keratitis in South India

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