Bacterial Keratitis in Toronto: A 16-Year Review of the Microorganisms Isolated and the Resistance Patterns Observed

Tam, Alex; Côté, Elie; Saldanha, Mário; Lichtinger, Alejandro; Slomovic, Allan R.

doi:10.1097/ico.0000000000001390

Cited by 45 publications

(54 citation statements)

References 46 publications

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“…The proportion of gram-negative bacteria among total bacterial keratitis has been increasing recently. Tam et al reported that the proportion of gram-negative bacterial keratitis increased from 19% in 2000–2003 to 30% in 2012–2015 [ 12 ]. Pseudomonas species has continued to be the most common isolate of gram-negative bacterial keratitis; the proportion varies among countries, ranging from 10% of cases in North America [ 12 – 14 ], 24.4% in Taiwan [ 15 ], 32.5% in South Korea [ 16 ], and up to 52% in South India [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of clinical characteristics and antibiotic susceptibility between Pseudomonas aeruginosa and P. putida keratitis at a tertiary referral center: a retrospective study

Cho

Lee

2018

BMC Ophthalmol

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BackgroundTo compare clinical characteristics and antibiotic susceptibilities in patients with Pseudomonas aeruginosa (PA) and P. putida (PP) keratitis at a tertiary referral center in South Korea.MethodsForty-nine cases of inpatients with culture-proven PA and PP keratitis were reviewed retrospectively between January 1998 and December 2017. We excluded cases of polymicrobial infection. Epidemiology, predisposing factors, clinical characteristics, antibiotic susceptibilities, and treatment outcomes were compared between the PA and PP groups. The risk factors for poor clinical outcome were evaluated on the basis of the total cohort and analyzed using multivariate logistic regression.ResultsA total of 33 eyes with PA keratitis and 16 eyes with PP keratitis were included. The mean age was 47.0 years in the PA group and 59.3 years in the PP group (p = 0.060). Differences were observed between the PA and PP groups in hypopyon (45.5% vs 6.3%, p = 0.006) and symptom duration (4.3 vs 9.5 days, p = 0.022). The most common predisposing factor for PA was wearing contact lenses (36.4%) and that for PP was corneal trauma (62.5%). No significant differences were observed in sex, previous topical steroid use, systemic disease, or duration of hospitalization between the two groups. The PA and PP groups both demonstrated good efficacy of colistin (both 100%), tobramycin (93.3%, 100%), ceftazidime (93.9%, 87.5%), and ciprofloxacin (96.6%, 87.5%). Imipenem (100% vs 81.3%, p = 0.030), piperacillin (96.6% vs 75%, p = 0.047), and ticarcillin (85% vs 0%, p < 0.001) showed significantly lower efficacy in the PP group than in the PA group. A poor clinical outcome was observed in 31.2% of the PA group and 37.5% of the PP group (p = 0.665). The risk factors for poor clinical outcome were previous ocular surface disease (odds ratio 10.79, p = 0.012) and hypopyon (odds ratio 9.02, p = 0.024).ConclusionsThe PA group was more closely associated with younger age, wearing contact lenses, shorter symptom duration, and hypopyon, whereas the PP group was more closely associated with elderly age, corneal trauma, and decreased efficacy of the beta-lactams. Clinical outcomes were not significantly different between the two groups. Previous ocular surface disease and hypopyon were the risk factors for poor clinical outcome.

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Section: Discussionmentioning

confidence: 99%

Comparison of clinical characteristics and antibiotic susceptibility between Pseudomonas aeruginosa and P. putida keratitis at a tertiary referral center: a retrospective study

Cho

Lee

2018

BMC Ophthalmol

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“…Intravenous use of antimicrobial antibodies has been proven effective for some infections such as Bezlotoxumab [35] in the treatment of Clostridium difficile toxin B and palivizumab [36] for respiratory syncytial virus and, as previously mentioned, MEDI3902 has been shown effective in Pseudomonas keratitis prophylaxis [3]. Since they are unconventional antimicrobials, microbes resistant to conventional antibiotics are less likely to have pre-existing resistance mechanisms to mAbs.…”

Section: Discussionmentioning

confidence: 99%

“…Future investigations can be done to determine its efficacy when given in combination with various broad-spectrum antibiotics which has been [41]. For example, tobramycin is often the standard for P. aeruginosa infections tobramycin's efficacy in the treatment of keratitis is limited [42], a previous study investigated the efficacy of tobramycin and MEDI3902 in combination [3]. Further investigation of possible combination treatments is worthy of consideration.…”

Section: Discussionmentioning

confidence: 99%

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Multifunctional Monoclonal Antibody Targeting Pseudomonas aeruginosa Keratitis in Mice

2020

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A worrisome trend in the study and treatment of infectious disease noted in recent years is the increase in multidrug resistant strains of bacteria concurrent with a scarcity of new antimicrobial agents to counteract this rise. This is particularly true amongst bacteria within the Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) designation. P. aeruginosa is one of the most common causes of bacterial keratitis. Therefore, it is of vital importance to characterize new antimicrobial agents with anti-Pseudomonal activity for use with the ocular surface. MEDI3902 is a multifunctional antibody that targets the P. aeruginosa persistence factor Psl exopolysaccharide, and the type 3 secretion protein PcrV. We initially assessed this antibody for ocular surface toxicity. The antimicrobial activity of the antibody was then tested by treating mice with established P. aeruginosa keratitis with both topical and intravenous treatment modalities. MEDI3902, was shown to be non-toxic to the ocular surface of mice when given topically. It was also effective compared to the control antibody at preventing P. aeruginosa keratitis with a one-time treatment at the time of infection. Both topical and intravenous administration of MEDI3902 has been proved significant in treating established keratitis infections as well, speeding the resolution of infection significantly more than that of the control IgG. We report the first use of a topical immunotherapeutic multifunctional agent targeting Psl and type 3 secretion on the ocular surface as an antimicrobial agent. While MEDI3902 has been shown to prevent Pseudomonas biofilm formation in keratitis models when given prophylactically intravitally, we show that MEDI3902 has the capability to also treat an active infection when given intravenously to mice with Pseudomonas keratitis. Our data indicate antibodies are well tolerated and nontoxic on the ocular surface. They reduce infection in mice treated concurrently at inoculation and reduced the signs of cornea pathology in mice with established infection. Taken together, these data indicate treatment with monoclonal antibodies directed against Psl and PcrV may be clinically effective in the treatment of P. aeruginosa keratitis and suggest that the design of further antibodies to be an additional tool in the treatment of bacterial keratitis.

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“…Furthermore, S. aureus and P. aeruginosa have been identified by the World Health Organization as 'High' and 'Critical' priority targets, in the development of new antibiotics [38]. Evidence of increasing antibiotic resistance among ocular isolates is provided by longitudinal studies [39,40] and of particular concern is the observation that resistance to fluoroquinolones is increasing for both Methicillin Susceptible (MSSA) and Methicillin Resistant (MRSA) S. aureus strains [40]. In the UK, fluoroquinolones are currently used as the first-line antibiotic in the treatment of bacterial keratitis [41].…”

Section: Antibiotic Resistance In Biofilmsmentioning

confidence: 99%

Corneal Infection Models: Tools to Investigate the Role of Biofilms in Bacterial Keratitis

Urwin

Okurowska

Crowther

et al. 2020

Cells

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Bacterial keratitis is a corneal infection which may cause visual impairment or even loss of the infected eye. It remains a major cause of blindness in the developing world. Staphylococcus aureus and Pseudomonas aeruginosa are common causative agents and these bacterial species are known to colonise the corneal surface as biofilm populations. Biofilms are complex bacterial communities encased in an extracellular polymeric matrix and are notoriously difficult to eradicate once established. Biofilm bacteria exhibit different phenotypic characteristics from their planktonic counterparts, including an increased resistance to antibiotics and the host immune response. Therefore, understanding the role of biofilms will be essential in the development of new ophthalmic antimicrobials. A brief overview of biofilm-specific resistance mechanisms is provided, but this is a highly multifactorial and rapidly expanding field that warrants further research. Progression in this field is dependent on the development of suitable biofilm models that acknowledge the complexity of the ocular environment. Abiotic models of biofilm formation (where biofilms are studied on non-living surfaces) currently dominate the literature, but co-culture infection models are beginning to emerge. In vitro, ex vivo and in vivo corneal infection models have now been reported which use a variety of different experimental techniques and animal models. In this review, we will discuss existing corneal infection models and their application in the study of biofilms and host-pathogen interactions at the corneal surface.

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Bacterial Keratitis in Toronto: A 16-Year Review of the Microorganisms Isolated and the Resistance Patterns Observed

Cited by 45 publications

References 46 publications

Comparison of clinical characteristics and antibiotic susceptibility between Pseudomonas aeruginosa and P. putida keratitis at a tertiary referral center: a retrospective study

Comparison of clinical characteristics and antibiotic susceptibility between Pseudomonas aeruginosa and P. putida keratitis at a tertiary referral center: a retrospective study

Multifunctional Monoclonal Antibody Targeting Pseudomonas aeruginosa Keratitis in Mice

Corneal Infection Models: Tools to Investigate the Role of Biofilms in Bacterial Keratitis

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