Keratitis and resistance to fluoroquinolones

The infectious keratitis is a pathological condition that poses significant risks to vision and, for this reason, is considered an ophthalmological emergency requiring immediate treatment. In fact, the incidence of endophthalmitis secondary to infectious keratitis ranges from 0.29% to 6% and the incidence of evisceration or enucleation surgery is still 1.8%. Globally, an estimated 1.5 to 2 million people develop bacterial keratitis each year. The most common cause of bacterial keratitis is gram-positive bacteria, but it can also be attributed to gram-negative bacteria, fungi and viruses.

The first-line treatment of microbial keratitis includes the administration of topical ophthalmic antibiotics. Depending on the severity of the disease, the associated risk factors and the microbiological agents suspected of causing it, one or two antimicrobial agents are generally used.

Fluoroquinolones and keratitis: increasing resistance

Some recent studiesconducted in Australia and New Zealand, found increased resistance to fluoroquinolones in bacteria isolated from corneal keratitis lesions.

In particular, one of these studies analysed a total of 501 corneal scrapings, performed on 498 patients, over a study period of nine years. A total of 272 culture-positive corneal scrapings (54%) were detected: 200 cultures allowed the isolation and identification of a single micro-organism and in the rest, several different micro-organisms were identified. 255 cultures were bacterial (94%) and there were also 11 fungal isolates (4%), 5 mixed bacterial-fungal isolates (2%) and 1 viral isolate (<1%).

Overall, 5% of the bacterial isolates were resistant to the fluoroquinolone ciprofloxacin, confirming similar rates reported in previous studies and in studies conducted in Australia. These data are alarming as they represent a 5-fold increase in ciprofloxacin resistance for microbial keratitis compared to the period from 2003 to 2007. In addition, the proportion of cultures that led to the growth of Pseudomonas aeruginosa has increased. 

In addition, a previous study in Melbourne found that the 63% isolates of Staphylococcus aureus methicillin-resistant (MRSA) were resistant to fluoroquinolones. Previous studies conducted in Queensland had reported that fluoroquinolone resistance among MRSA isolates was 14% and 20% respectively, suggesting a significant increase in fluoroquinolone resistance among MRSA isolates and a general trend of increasing fluoroquinolone resistance in bacterial keratitis.

These new studies refer to data collected in a specific region of the globe, but considered a large number of isolates, over a very long time and all evaluated using a standardised test protocol that did not vary throughout the duration of the study.

The importance of surveillance programmes

The study authors note that surveillance programmes may be necessary to monitor changes in antimicrobial resistance of bacteria causing keratitisinfectious. The trend of increasing antimicrobial resistance, including the discovery of strains of Pseudomonas aeruginosa resistant to fluoroquinolones, is indeed worrying. Furthermore, the World Health Organisation recommends a 5% increase in resistance as an appropriate threshold for re-evaluating protocols for the empirical treatment of neonatal sepsis and sexually transmitted infections, a threshold also reached in these studies for bacterial keratitis. 

Therapeutic alternatives 

Recent studies revealed that both gram-positive and gram-negative organisms are more sensitive to netilmicin (92.9%), an antibiotic belonging to the aminoglycoside family and a water-soluble, modified (N-ethyl) semi-synthetic derivative of isomycin, produced by the fermentation of Micromonospora inyoesis. Among the available antibiotic treatments, netilmicin maintains high efficacy in the treatment of both monomicrobial and polymicrobial keratitis. Netilmicin should, therefore, be considered among the first choices for the management of microbial keratitis from the earliest symptoms.

1. Scott DAR, Mansell C, McKelvie J. Bacteria identified on corneal scrapes demonstrate increasing resistance to fluoroquinolones in New Zealand. Clin Exp Ophthalmol. 2022 Apr;50(3):352-354.
2. González-Dibildox LA, Oyervidez-Alvarad JA, Vazquez-Romo KA, Ramos-Betancourt N, Hernandez-Quintela E, Beltra F, Garza-Leon M. Polymicrobial Keratitis: Risk Factors, Clinical Characteristics, Bacterial Profile, and Antimicrobial Resistance. Eye Contact Lens. 2021 Aug 1;47(8):465-470.