Nontuberculous Mycobacterial Keratitis Research Articles

Clinico-microbiological Profile of Nontuberculous Mycobacterial Keratitis

PurposeTo assess the clinical and microbiological characteristics of nontuberculous mycobacterial (NTM) keratitis and to evaluate their response to medical therapy.MethodsSixteen patients of NTM keratitis were retrospectively reviewed from May 2014 to May 2019. Laboratory diagnosis were made using Ziehl-Nielsen acid-fast staining, routine culture method of isolation of nontuberculous mycobacteria and further identification of species by PCR (polymerase chain reaction)-based DNA sequencing targeting the heat shock protein-65 (hsp-65) gene.ResultsSixteen patients of microbiologically proven NTM keratitis were included. The average age at the time of presentation was 43.56 years (range, 24–73 years). The mean duration of symptoms was 2.23 months. The commonest risk factor was injury with organic material (43.7) followed by ocular surgery (25%). The majority of the nontuberculous mycobacteria were Mycobacterium abscessus (87.6%) followed by M. fortuitum (6.2%) and M. chelonae (6.2%). The in vitro sensitivity showed maximum sensitivity to Amikacin (AMK; 100%) followed by Azithromycin (AZM; 85.7%), and Clarithromycin (CLR; 85.7%). Out of a total of 16 patients, 12 (75%) had total success with medical therapy while 4 (25%) required surgical intervention.ConclusionThis study is focused on rapid and reliable identification of NTM keratitis through PCR-based identification method to enable effective medical management. The antibiotic susceptibility testing of different subspecies of NTM further reduced the need for surgical intervention. The effective role of AMK either alone or in combination with macrolide antibiotics is also highlighted in this study.

Outcomes of Nontuberculous Mycobacterial Keratitis After Clear Corneal Incision Phacoemulsification Surgery: A Case Series of 6 Eyes in South Florida.

The purpose of this study was to present the successful management and outcomes in a series of 6 cases of culture-positive nontuberculous mycobacterial keratitis after clear corneal incision phacoemulsification surgery. This is a case series of 6 consecutive eyes that presented at the Cornea Division at an academic institution, diagnosed with culture-positive nontuberculous mycobacterial keratitis after phacoemulsification surgery. Six eyes of 5 patients were included. The mean interval from cataract surgery to presentation was 7.7 weeks. All cases presented with intrastromal abscesses adjacent to corneal incisions, and 2 had scleral extension of the infection. Isolated organisms were Mycobacterium abscessus (n = 4), Mycobacterium chelonae (n = 1), and Mycobacterium mucogenicum (n = 1). All cases were treated with topical amikacin 8 mg/mL for 10.5 weeks on average. All cases received either oral clarithromycin at 500 mg twice-daily dosage or oral azithromycin at 500 mg daily. Two patients with scleral abscesses underwent surgical debridement with amniotic membrane grafts. All 6 eyes achieved infection resolution and good visual recovery, with the final visual acuity ranging from 20/20 to 20/60. None of the patients experienced recurrence of infection. Prompt medical treatment with combined topical and oral therapy can lead to infection resolution and favorable visual recovery. Early surgical intervention can ensure good outcomes in cases of scleral extension.

Discovery of novel antimycobacterial drug therapy in biofilm of pathogenic nontuberculous mycobacterial keratitis

PurposeThe potential of slow-growing mycobacteria to form biofilms in human tissues contributes to the problem of establishing an effective treatment strategy. The purpose of this study was to examine new antibiotic strategies to enhance current treatment options for these infections. MethodsSensitivities of Mycobacterium fortuitum ATCC 49404 and Mycobacterium chelonae ATCC 35752 were evaluated for different antimicrobials singly and in combination using broth microdilution and FICI (Fractional Inhibitory Concentration Index) synergy screening. Anti-biofilm effects were evaluated in an 8-well chamber slide biofilm model. The efficacy of a new treatment strategy was validated using the novel neutropenic mouse keratitis model and monitored by slit-lamp microscopy, confocal microscopy, and colony forming unit measurements. ResultsWe reported the very first evidence that these organisms develop corneal biofilms by the accumulation of extracellular DNA (eDNA) and the presence of microcolonies using a novel mycobacterial neutropenic mouse keratitis model. The combination of amikacin and gatifloxacin or besifloxacin was more effective than the current gold-standard drug, amikacin, and we developed a novel treatment strategy (amikacin + gatifloxacin + DNase), the destruction of biofilm matrix component, eDNA, which increased the efficacy of the new antibiotic combination for treating mycobacterial infection in in vitro (P = 0.002) and in vivo (P = 0.001) compared to its respective control. ConclusionBiofilms have a role in mycobacterial keratitis leading to poor treatment outcomes in clinical practice and the use of combination therapy (amikacin + gatifloxacin + DNase) could be a useful new treatment option.

Biofilms of Pathogenic Nontuberculous Mycobacteria Targeted by New Therapeutic Approaches.

Microbial infections of the cornea are potentially devastating and can result in permanent visual loss or require vision-rescuing surgery. In recent years, there has been an increasing number of reports on nontuberculous mycobacterial infections of the cornea. Challenges to the management of nontuberculous mycobacterial keratitis include delayed laboratory detection, low index of clinical suspicion, poor drug penetration, slow response to therapy, and prolonged use of antibiotic combinations. The ability of nontuberculous mycobacteria to evade the host immune response and the ability to adhere and to form biofilms on biological and synthetic substrates contribute to the issue. Therefore, there is an urgent need for new antimicrobial compounds that can overcome these problems. In this study, we evaluated the biofilm architectures for Mycobacterium chelonae and Mycobacterium fortuitum in dynamic flow cell chamber and 8-well chamber slide models. Our results showed that mycobacterial biofilms were quite resistant to conventional antibiotics. However, DNase treatment could be used to overcome biofilm resistance. Moreover, we successfully evaluated a new antimicrobial compound (AM-228) that was effective not only for planktonic mycobacterial cells but also for biofilm treatment and was compared favorably with the most successful “fourth-generation” fluoroquinolone, gatifloxacin. Finally, a new treatment strategy emerged: a combination of DNase with an antibiotic was more effective than an antibiotic alone.

In Vitro Antibiotic Susceptibility of Rapidly Growing Nontuberculous Mycobacteria Isolated from Patients with Microbial Keratitis

Purpose: This study was undertaken to determine the antibiotic susceptibility and minimum inhibitory concentrations (MIC) of amikacin, tobramycin, ciprofloxacin, gatifloxacin, azithromycin, and clarithromycin against rapidly growing nontuberculous mycobacteria isolated from patients with keratitis.Methods: A total of 15 rapidly growing nontuberculous mycobacteria isolated from corneal scrapings of keratitis patients from January 1999 through December 2007 were subjected to antimicrobial susceptibility testing by the E-Test to amikacin, tobramycin, ciprofloxacin, gatifloxacin, azithromycin, and clarithromycin.Results: Out of 15 isolates, 13 were identified as Mycobacterium chelonae complex and 2 as Mycobacterium fortuitum complex. Based on minimum inhibitory concentration (MIC) cut off, all 15 (100%) isolates were sensitive to amikacin, azithromycin, and clarithromycin, 13 (86%) were sensitive to tobramycin, nine (60%) to gatifloxacin, and only 6 (40%) to ciprofloxacin. The MIC range was 0.25–4 µg/ml for amikacin, 0.5–1 µg/ml for azithromycin, 0.125–1 µg/ml for clarithromycin, 0.5–16 µg/ml for ciprofloxacin, and 0.25–16 µg/ml for tobramycin. MIC90 for amikacin was 2 µg/ml, azithromycin 1 µg/ml, clarithromycin 0.75 µg/ml, ciprofloxacin 8 µg/ml, gatifloxacin 8 µg/ml, and for tobramycin it was 4 µg/ml.Conclusions: All the isolates were sensitive to amikacin, azithromycin, and clarithromycin, but the MIC values of clarithromycin and azithromycin were lower than amikacin. Based on in vitro susceptibility results it appears that the topical amikacin in combination with oral clarithromycin or azithromycin is the best treatment option for rapidly growing nontuberculous mycobacterial keratitis.

The diagnosis and treatment of rapidly growing non-tuberculous mycobacterial keratitis

To study the clinical features, diagnosis and treatment of non-tuberculous mycobacterial keratitis (NTMK). It was retrospective case series study. Twelve eyes in 12 patients with NTMK following corneal foreign body trauma in 2007 were studied retrospectively including the case histories, clinical findings, laboratory examinations, diagnosis, treatment and prognosis. The main laboratory examination included corneal scrapings by culturing, polymerase chain reaction (PCR) and transmission electron microscopy (TEM), corneal lesions by histopathologic examinations and TEM. The patients received local and systemic antibiotics therapy, lesion cleaning followed by cauterization with tincture of iodine (5%) and (or) keratoplasty. All cases had a history of corneal trauma, there was corneal metallic foreign body removal at one hospital in 11 cases, corneal reed trauma in 1 case. The characteristic signs involved grayish-blue crystalloid keratopathy, multifocal infiltrates, satellites, radical form changes in the Descemet's membrane. The results of laboratory examinations of the scrapings of the cornea infection were as follows: all cultures (12/12) were positive for rapidly growing mycobacteria, and isolates from 5 patients were all diagnosed as mycobacterium chelonae subspecies abscess; acid-fast staining revealed positive bacilli in all the 4 patients; seven of 8 patients were positive for bacterium by PCR. Transmission electron microscopy in all the 3 specimens showed many slender rod-shaped or short coarse-shaped bacteria which were phagocytized by monocytes, and some necrotic tissue. Infections in 10 eyes were resolved by combined treatment regimen including a combination of antimicrobial agents (amikacin, rifampin, gatifloxacin, ciprofloxacin, azithromycin and/or ofloxacin, etc.) and local lesion cleaning followed by cauterization with 5% tincture of iodine within 2-5 months; two cases resolved by keratoplasty which poorly responded to antibiotic therapy for 6 months. NTMK is a rare, recalcitrant opportunistic infection which can occur in an epidemic fashion following corneal foreign body trauma. The diagnosis of NTMK is difficult, and may easily be misdiagnosed as fungal keratitis. Acid-fast staining, TEM, especially bacterial culture can help to obtain definitive diagnosis. NTMK has a long response period to medical management. The majority of patients can be cured by local and systemic antibiotics therapy, and the recalcitrant infections could be resolved by keratoplasty.

Treatment of gatifloxacin for experimental non-tuberculous mycobacterial keratitis in rabbit

目的 探讨加替沙星对兔非结核分枝杆菌(NTM)性角膜炎的治疗效果.方法 利用龟分枝杆菌建立兔NTM角膜炎模型,随机分为6组,分别使用加替沙星、左氧氟沙星、环丙沙星、阿米卡星及加替沙星联合阿米卡星进行治疗,平衡盐溶液(BSS)作为对照;观察治疗前后角膜浸润面积及临床表现的变化,并对治疗1周后的角膜病灶进行细菌定量分析.结果 加替沙星可抑制角膜组织内NTM的生长,使NTM角膜炎角膜浸润面积明显减小,与阿米卡星联合使用可增强其抗菌作用.结论 加替沙星是治疗NTM角膜炎的有效药物之一。

Nontuberculous (Atypical) Mycobacterial Keratitis After LASIK

Corneal infection with unfamiliar organisms such as nontuberculous (atypical) mycobacteria after laser in situ keratomileusis (LASIK) can be a significant clinical problem, and mismanagement of such corneal infection in an otherwise healthy, young individual can lead to significant medicolegal issues for the refractive surgeon. Because nontuberculous (atypical) mycobacterial keratitis is the most common infection after LASIK, the refractive surgeon should be aware of all aspects of this dreaded infection to be better prepared to manage such cases. Literature search. This article provides a comprehensive compilation of all reported cases of nontuberculous (atypical) mycobacterial keratitis in the English literature and provides some useful recommendations for the clinical management of such corneal infection after LASIK.

Clinical characteristics of microbial keratitis in a university hospital in Taiwan

PurposeTo analyze the clinical and microbiological characteristics of microbial keratitis at the National Taiwan University Hospital in the preceding 10 years. DesignRetrospective cross-sectional study. MethodsMedical records were reviewed for all patients with clinically diagnosed microbial keratitis presenting at the National Taiwan University Hospital from January 1992 to December 2001. Risk factors, microbial isolations, clinical patterns, treatment, and outcomes were analyzed. ResultsMicrobial keratitis was diagnosed for 476 eyes in 453 patients (220 female and 233 male; mean age, 40.7 years). Pseudomonas species were the most commonly isolated organisms (37.7%), followed by fungi (13.5%), staphylococci (8.4%), nontuberculous mycobacteria (7.9%), streptococci (7.6%), and Acanthamoeba (4.4%). Contact-lens wear was the most common predisposing factor (44.3%). Medical treatment was successful for a total of 344 eyes (72.3%), with 132 eyes (27.7%) requiring surgery. The duration from symptom onset to diagnosis of microbial keratitis was statistically significantly shorter for the cases treated medically than the cases treated surgically (7.70 ± 14.37 and 20.53 ± 28.85 days, respectively, p = .000000332). Response to medical treatment was more favorable for bacterial infection (except nontuberculous mycobacterial infection) as compared with fungal or Acanthamoeba infection. A total of 84.4% of pseudomonal keratitis cases were cured by medical treatment, while 85% of nontuberculous mycobacterial keratitis cases eventually required surgical treatment to control the infection. ConclusionContact-lens related pseudomonal keratitis was the most common form of microbial keratitis in Taiwan. Early diagnosis and prompt treatment are important for successful management of microbial keratitis.

Epidemic and sporadic cases of nontuberculous mycobacterial keratitis associated with laser in situ keratomileusis

Purpose To report national case-finding results for nontuberculous mycobacterial keratitis and describe its association with laser in situ keratomileusis (LASIK). Design Enhanced passive disease reporting. Methods In April 2001, we investigated a California cluster of Mycobacterium chelonae keratitis associated with hyperopic LASIK using a contact lens mask. To identify other possibly related cases, the American Academy of Ophthalmology e-mailed its members asking them to report recent cases of nontuberculous mycobacterial keratitis to the Centers for Disease Control and Prevention. Results Forty-three additional cases of keratitis were reported (onsets between August 2000 and June 2001). Of these, 31 occurred as part of two unrelated LASIK-associated outbreaks. The 12 other reported cases occurred in sporadic fashion. Of the latter cases, 4 were associated with LASIK surgery. None of the reported cases were related to the M. chelonae cluster in California. Conclusions Laser in situ keratomileusis-associated keratitis with nontuberculous mycobacteria may be more common than previously known.

Cluster of Mycobacterium Chelonae keratitis cases following laser in-situ keratomileusis

PURPOSE: To describe a cluster of Mycobacterium chelonae keratitis cases involving patients who underwent laser in-situ keratomileusis (LASIK) at a single refractive surgery center. DESIGN: Descriptive case series of four patients and cohort study to identify disease associations. METHODS: Examination schedules, diagnostic tests, and therapy were based on best medical judgment. Isolates from three patients were compared by pulsed-field gel electrophoresis. Epidemiologic studies were performed to identify the source of infection. RESULTS: Seven of eight eyes developed M. chelonae keratitis following bilateral simultaneous LASIK. Each patient was thought to have diffuse lamellar keratitis initially, but all seven eyes were noted to have opacities suggestive of infectious keratitis by 13 to 21 days after surgery. All eyes had undergone hyperopic LASIK over four days in April 2001 by one surgeon in a community-based refractive surgery center. A cohort study of all patients undergoing LASIK at the same center in April 2001 revealed that M. chelonae keratitis occurred only in persons undergoing correction of hyperopia (seven of 14 eyes vs. none of 217 eyes undergoing myopic LASIK, P < .001). The only difference identified between procedures was use of masks created from a soft contact lens in hyperopic LASIK. Three isolates (three patients) were indistinguishable by pulsed-field gel electrophoresis. Eyes were treated with a combination of antimicrobial agents, including topical azithromycin in three patients, with resolution of infection in all eyes over 6 to 14 weeks. The source of infection was not identified on environmental cultures. CONCLUSION: Postoperative nontuberculous mycobacterial keratitis can occur in an epidemic fashion following LASIK. Topical amikacin, azithromycin, clarithromycin, ciprofloxacin, or a combination of these agents, appears to be effective treatment for these infections.

Nontuberculous mycobacterial keratitis in south Florida

Objective This study aimed to review the clinical features, therapeutic response, and histopathology of cases of nontuberculous mycobacterial keratitis at the Bascom Palmer Eye Institute. Design and participants Retrospective review of medical records, clinical photographs, histopathology, and microbiology of 24 cases of nontuberculous acid-fast keratitis over the past 15 years. Results Causal organisms included Mycobacterium chelonae (16), M. fortuitum (3), M. avium-intracellulare (2), M. nonchromogenicum (1), M. triviale (1), and M. asiaticum (1). Clinically, the keratitis had a superficial location except in those patients with a history of surgery. Amikacin was the most commonly used antibiotic (63%). Three patients were treated with Clarithromycin. In one patient, it was stopped because of toxicity; the other two had resolution of their infiltrates. Fifty-five percent did not respond to topical antimicrobial therapy. The organisms as a group were sensitive to amikacin and Clarithromycin and resistant to the fluoroquinolones. Sixty-four percent of the group that failed to respond to medical treatment were treated with steroids after the diagnosis was known, in comparison to 44% of the group treated successfully with medications. The histopathology of the patients treated with steroids showed minimal inflammation despite a large number of organisms, in contrast to the dense infiltrates seen in the specimens from patients not treated with topical steroids. Conclusion Nontuberculous mycobacterial keratitis is a chronic insidious infection that is often unresponsive to medical therapy. The authors recommend that steroids be withheld. Based on the authors’ experience of three patients, topical Clarithromycin may hold promise as a therapeutic agent. Lamellar keratectomy or penetrating keratoplasty should be considered in those patients who do not respond to medical therapy or those who have recurrent exacerbations on attempted weaning of topical antibiotic therapy.

Clinicopathologic Study of Satellite Lesions in Nontuberculous Mycobacterial Keratitis

Multifocal stromal infiltrates or “satellite lesions” have been considered a characteristic feature of fungal keratitis. We examined two patients with nontuberculous mycobacterial keratitis who clinically presented with satellite lesions. The keratitis consisted of multifocal stromal infiltrates with indistinct white and fluffy margins. Both patients received topical fortified amikacin therapy with poor response. Lamellar keratectomy or penetrating keratoplasty was performed, respectively, in the two patients because of progressive stromal thinning and enlarging satellite lesions. Histopathologically, the main lesions consisted of dense infiltration of inflammatory cells with numerous acid-fast bacilli, while the satellite lesions were composed chiefly of inflammatory cells with fewer mycobacteria. Besides fungal keratitis, nontuberculous mycobacterial keratitis should also be considered when satellite lesions are present.

Topical ciprofloxacin for treating nontuberculous mycobacterial keratitis

This study aimed to evaluate the clinical efficacy of topical ciprofloxacin for treating Mycobacterium fortuitum and Mycobacterium chelonae keratitis refractory to amikacin therapy. A prospective clinical trial of topical ciprofloxacin treatment for nontuberculous mycobacterial keratitis was conducted. Eleven patients with nontuberculous mycobacterial keratitis diagnosed from 1992 to 1996 were enrolled. All 11 patients were treated initially with topical fortified amikacin, but only 2 patients responded. The other nine patients, four with M. fortuitum and five with M. chelonae keratitis, were refractory to amikacin therapy and received topical ciprofloxacin treatment. Bacterial culture and drug susceptibility tests using the broth microdilution method were performed on all 11 patients. The clinical response to amikacin or ciprofloxacin treatment was judged by corneal re-epithelialization and density and/or size of corneal infiltrates. M. chelonae isolates were more resistant to amikacin and ciprofloxacin than M. fortuitum isolates based on the in vitro susceptibility test. Clinically, three patients with M. fortuitum keratitis were responsive to ciprofloxacin therapy; however, only one patient with M. chelonae keratitis responded to the same therapy. Topical ciprofloxacin offers a therapeutic alternative for nontuberculous mycobacterial keratitis, which was refractory to amikacin treatment. However, topical ciprofloxacin was more effective for treating M. fortuitum keratitis than for M. chelonae keratitis.

Extensive Lamellar Keratectomy for Treatment of Nontuberculous Mycobacterial Keratitis

To determine the efficacy of using extensive lamellar keratectomy for treating patients who have nontuberculous mycobacterial keratitis that is unresponsive to medical treatment. Nine patients with bacteriologically proven nontuberculous keratitis, who had poor response to medical treatment and whose corneal infiltrate was not deeper than 80% of corneal thickness, were selected for extensive lamellar keratectomy. This procedure was performed freehand to remove all the corneal infiltration visible by operation-microscopic examination, to have a clean stromal bed. Corneal infection was eradicated in seven patients by a single procedure. In the other two patients, the condition was controlled by a second operation. Epithelialization was rapid and complete in all cases within ten days (mean, 4.8 days). Pain relief was dramatic after surgery. Visual acuity after surgery was improved in seven patients, but remained the same in two. There were no complications as a result of the lamellar keratectomy. Lamellar keratectomy should be considered as a treatment option for patients with nontuberculous mycobacterial keratitis who are unresponsive to medical therapy.

Comparative Efficacy of Topical Ciprofloxacin for Treating: Mycobacterium fortuitum and Mycobacterium chelonae Keratitis in an Animal Model

Mycobacterium fortuitum and M. chelonae are the two most common causes of nontuberculous mycobacterial keratitis, and they may be difficult to differentiate at diagnosis. Mycobacterium fortuitum is generally more sensitive to ciprofloxacin in vitro than is M. chelonae. Using a rabbit model, we compared the efficacy of topical ciprofloxacin (3 mg/ml) against M. chelonae keratitis to its efficacy against M. fortuitum keratitis. After four days of therapy, ciprofloxacin significantly reduced the number of both organisms in treated eyes compared to untreated control eyes (both P values < .001). Mean culture ratios (colony-forming units in treated eye divided by colony-forming units in untreated eye for each rabbit) were used to compare efficacy between groups. When all treated animals were considered, no significant difference was found between groups (P = .13). When outlier values were excluded, ciprofloxacin was more effective against M. fortuitum than M. chelonae (P = .01). When treated and untreated eyes were compared after therapy in the M. fortuitum group, ciprofloxacin treatment was associated with a reduction in mean stromal infiltrate area (P = .03) and in the tendency to form satellite lesions (P = .07). A clinical effect was not observed in the M. chelonae group. Although ciprofloxacin is effective against both organisms, it appears to be less effective against M. chelonae than M. fortuitum in vivo.