Proteus mirabilis Keratitis: Risk Factors, Clinical Features, Treatment Outcomes, and Microbiological Characteristics.

PURPOSE: To characterize the risk factors, clinical presentations, management choices, and outcomes of Proteus mirabilis keratitis. METHODS: In this retrospective study, 26 culture-proven cases of P. mirabilis infections were diagnosed and treated between 1998 and 2019 at the University of Pittsburgh Medical Center. Medical records were available for 14 keratitis cases and were reviewed for demographic information, ocular risk factors, and treatment outcomes. RESULTS: Sixteen eyes of 14 patients were included in the study. The average age was 47.8 ± 19.3 years, with a median follow-up time of 6 months. The most common ocular risk factors were poor ocular surface and contact lens use in 57.1% and 42.9% of cases, respectively. Eleven of the 14 patients (78.6%) had positive corneal cultures, and 13 of the 14 patients (92.9%) had positive conjunctiva or eyelid cultures. All isolates were susceptible to ciprofloxacin, ofloxacin, moxifloxacin, gatifloxacin, and cefazolin. Surgical intervention was required in 4 patients (28.6%). Average LogMAR visual acuity was 1.3 ± 1.0 at presentation and 0.9 6 ± 1.0 at the most recent follow-up visit. CONCLUSIONS: Proteus mirabilis is an uncommon cause of microbial keratitis. Patients with poor ocular surface and those who use contact lens are at increased risk for developing this cause of keratitis. Empiric treatment with fortified antibiotics or fluoroquinolones seemed to provide effective coverage for P. mirabilis.

Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis.

Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage ΦEF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of E. faecalis Phage ΦEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with E. faecalis-related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 × 104 cells) into the vitreous. The number of viable bacteria in the eye increased to >1 × 107 CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of ΦEF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of E. faecalis.

Potential Alternative Treatment of Ocular Bacterial Infections by Oil Derived from Syzygium aromaticum Flower (Clove).

Purpose/Aim: This study aims to evaluate the predisposing risk factors and antibiotic resistance of bacterial corneal ulcer to commonly used antibiotics. In addition, assess the in vitro efficacy of plant-derived essential oils (EOs) as safe and effective antimicrobial agents. METHODS: Demographic features and predisposing risk factors of corneal ulcer patients were recorded. Isolation and identification of bacteria was performed using conventional microbiological methods. Antibacterial activity was determined by disk diffusion and the micro-dilution broth methods. EOs were extracted by steam distillation and were analyzed by gas chromatography mass spectrometry technique. RESULTS: Out of the 200 patients with corneal ulcer evaluated in this study, the main predisposing factor of bacterial corneal ulcer was trauma (26.5%) and 96.7% isolates were multidrug resistant. Staphylococcus aureus was the predominant isolate 33 cases. Antibiotic susceptibility of bacterial isolates showed that the fourth-generation fluoroquinolones, gatifloxacin was the most effective antibiotic with sensitivity rate 81.3%. Seven selected EOs showed significant activity against most of the tested bacteria. Syzygium aromaticum oil showed high activity against all tested bacterial species with highest sensitivity rate (97.5%) and low minimal inhibitory concentration values against S. aureus (0.10 µl/ml). The chemical composition of the EOs showed that the monoterpenes were predominant. The main constituent of S. aromaticum oil was eugenol (76%). CONCLUSIONS: The current study showed that S. aromaticum oil had high antibacterial activity that could be helpful in the treatment of ocular bacterial infections to minimizing the possible side effects of commonly used antibiotic.

Drugs - Do we need them? Applications of non-pharmaceutical therapy in anterior eye disease: A review.

Natural products have been in use long before the introduction of modern drug therapies and are still used in various communities worldwide for the treatment of anterior eye disease. The aim of this review is to look at the current non-pharmaceutical modalities that have been tried and assess the body of existing evidence behind them. This includes alternative medicine, existing non-pharmaceutical therapy and more recent low and high tech solutions. A detailed search of all available databases including MEDLINE, Pubmed and Google was made to look for English-language studies for complementary and alternative treatment modalities (CAM), natural therapies and new modalities for anterior eye disease such as blepharitis, dry eye and microbial keratitis. We have included a broad discussion ranging from traditional treatments like honey and aloe vera which have been used for centuries, to the more recent technological advances like Intense Pulsed Light (IPL), LipiFlow and photoactivated chromophore for corneal cross linking in infectious keratitis (PACK-CXL). Alternative management strategies may have a role in anterior eye diseases and have a potential in changing the way we currently approach them. Some of the available CAM could play a role if incorporated in to current management practices of not only chronic diseases like blepharitis and dry eye, but also acute conditions with significant morbidity like microbial keratitis. Further large-scale randomized control trials stratified by disease severity are required to improve our understanding and to evaluate the use of non-pharmaceutical therapy against current practice.

Adjunctive Therapies for Bacterial Keratitis.

Bacterial keratitis is the most common type among all types of infectious keratitis. Currently, antibiotics are the main-stay of treatment. The objective of this systematic review is to review published clinical studies which discuss the adjunctive treatment of bacterial keratitis to guide clinical decision-making. We reviewed the role of a variety of medications and surgeries which can help in managing bacterial keratitis complications, which include as thinning, perforation, and impaired wound healing. We have included appropriate animal and laboratory studies, case reports and case series, and randomized clinical trials regarding each therapy.

An Eye Popping Case of Orbital Necrotizing Fasciitis Treated with Antibiotics, Surgery, and Hyperbaric Oxygen Therapy.

BACKGROUND Necrotizing fasciitis (NF) of the orbit is a rare and deadly condition that requires prompt surgical and medical management to decrease morbidity and mortality.  CASE REPORT Here we present an interesting case of an individual who developed fulminant NF of the left orbit requiring emergent surgical intervention, antibiotics, and subsequent hyperbaric oxygen therapy in an attempt to save the eye.  CONCLUSIONS With an early and aggressive multifaceted approach using antibiotics, surgery, and hyperbaric oxygen it may be possible to preserve eye structure and function. Without treatment NF is a rapidly progressive condition and can result in significant morbidity.

Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies.

Purpose: To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis. Methods: We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety. Results: Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea. Conclusions: Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted.

Endophthalmitis Caused by Nontuberculous Mycobacterium: Clinical Features, Antimicrobial Susceptibilities, and Treatment Outcomes.

PURPOSE: To report the clinical features, antibiotic susceptibilities and treatment outcomes in patients with endophthalmitis caused by nontuberculous mycobacterium. DESIGN: Noncomparative, consecutive case series. METHODS: Retrospective chart review between December 1990 and June 2014. RESULTS: In the 19 study patients, the clinical setting of endophthalmitis included post-cataract surgery (7/19, 36.8%), post-glaucoma implant (6/19, 31.6%), post-intravitreal injection (2/19, 10.5%), endogenous endophthalmitis (2/19, 10.5%), post-pars plana vitrectomy (1/19, 5.3%), and post-scleral buckle exposure (1/19, 5.3%). Chronic recurrent or persisting ocular inflammation was present in 15 of 19 patients (78.9%). The species isolated were Mycobacterium chelonae in 14 patients (73.7%), M fortuitum in 3 patients (15.8%), M triplex in 1 patient (5.3%), and M avium intracellulare in 1 patient (5.3%). Antibiotic susceptibilities to tested isolates were the following: amikacin (14/16; 87.5%) and clarithromycin (12/16, 75.0%). Intravitreal injections of amikacin (0.4 mg/0.1 mL) were given in 14 of 19 patients (73.7%) with an average of 7 injections per patient (range, 1-24 injections). Intraocular lens removal was performed for 6 of 7 patients (85.7%) with post-cataract surgery endophthalmitis. All the patients with glaucoma implant (6/6, 100%) underwent implant removal. At last follow-up, 6 of 19 patients (31.6%) had best-corrected visual acuity of 20/400 or better. CONCLUSION: Endophthalmitis caused by nontuberculous mycobacterium often included chronic recurrent or persistent intraocular inflammation and frequently required removal of ocular device (intraocular lens, glaucoma implant, or scleral buckle). The majority of the isolates were susceptible to amikacin and clarithromycin. Visual outcomes in these patients even after treatment were generally poor.

Comparison Between Polymicrobial and Fungal Keratitis: Clinical Features, Risk Factors, and Outcome.

PURPOSE: To compare the clinical features, risk factors, and outcome of polymicrobial keratitis with monomicrobial keratitis due to fungus. DESIGN: Retrospective, comparative interventional case series. METHODS: Consecutive cases of microbial keratitis with significant growth of more than 1 organism in culture and culture-proven fungal keratitis treated with natamycin alone were retrieved from the microbiology department. Complete success was defined as resolution of the infiltrate with scar formation on medical treatment, partial success as resolution following tissue adhesive application, and failure as inadequate response to medical therapy with increasing infiltrate size, corneal melting, and/or perforation necessitating therapeutic penetrating keratoplasty (PKP) or evisceration. RESULTS: There were 34 eyes of 34 patients with polymicrobial keratitis and 60 cases of fungal keratitis. Compared to patients with fungal keratitis, patients with polymicrobial keratitis were significantly older (50.03 ± 9.81 years vs 42.79 ± 12.15 years, P = .0038), with larger infiltrates at presentation (61.8% vs 24.1%, P = .0007), a higher association with endophthalmitis (11.8% vs 0%, P = .03), previous history of corneal graft (20.6% vs 0%, P = .0012), and prior topical corticosteroid use (23.5% vs 5%, P = .019). In the polymicrobial group, a combination of bacteria and fungus was more frequently isolated (23, 67.6%), among which filamentous fungi (25, 39.1%) and coagulase-negative staphylococci (14, 21.9%) comprised a majority. Complete success was significantly lower in the polymicrobial group compared to the fungal keratitis group (39.3% vs 73.7%, P = .0045). In multivariate logistic regression analysis comparing factors affecting the outcome between the 2 groups, older age (P = .027) and ulcers larger than 6 mm (P = .001) at presentation adversely affected outcome. CONCLUSIONS: Polymicrobial keratitis with fungus and bacteria was more common and more challenging to treat, with a poorer outcome than fungal keratitis. Medical treatment may be effective; however, therapeutic PKP provided globe salvage at best. Early PKP may be advocated for larger ulcers at presentation.

Vitrectomy using 0.025% povidone-iodine in balanced salt solution plus for the treatment of postoperative endophthalmitis.

PURPOSE: To investigate the bactericidal effect of 0.025% povidone-iodine in Balanced Salt Solution PLUS (0.025% PI-BSS PLUS) and its use in vitrectomy for postoperative endophthalmitis. METHODS: First, an experimental laboratory model using Staphylococcus aureus was used to evaluate the bactericidal effect of PI-BSS PLUS. Next, in a case series of 4 eyes with postoperative endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS as irrigation solution was conducted, followed by postoperative intravitreal and intravenous antibiotics. RESULTS: In in vitro study, PI at concentrations of 0.01% and above in BSS PLUS exhibited marked bactericidal effect after 15 seconds of exposure. Bactericidal effect of 0.025% PI-BSS PLUS was maintained at room temperature storage for 15 minutes but was attenuated after 30 minutes. Among 4 eyes that underwent vitrectomy using 0.025% PI-BSS PLUS, coagulase-negative Staphylococcus sp. was isolated in 1 eye at the beginning but not at completion of surgery. In all four eyes, endophthalmitis was resolved with no adverse events. Ocular toxicity was not observed. CONCLUSION: The 0.025% PI-BSS PLUS is bactericidal and nontoxic when used as irrigation solution in vitrectomy. In 4 cases of postoperative endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS followed by postoperative antibiotics resolved endophthalmitis.

Negative pressure wound therapy in preseptal orbital cellulitis complicated with necrotizing fasciitis and preseptal abscess.

PURPOSE: Preseptal cellulitis (PC) may be locally complicated with abscess formation and necrotizing fasciitis. If not treated promptly and adequately, it may result in further complications. The authors report a series of patients where negative pressure wound therapy (NPWT) proved a safe and valuable adjunct therapy in avoiding complications of PC and in accelerating wound healing. METHODS: A 4 patient case series. Four male patients (11 months to 58 years old) with unilateral complicated PC. INTERVENTIONS: Patients were admitted with PC and treated initially with specific intravenous antibiotic therapy. These patients did not respond adequately; therefore, surgical drainage and/or debridement were performed. After surgery, persistent edema and purulent discharge was observed prompting the need for adjunct NPWT every 48 to 72 hours. NPWT is the use of vacuum through a wound filler material covered with an airtight drape connected to a pump. Complete ophthalmologic examination was performed after each 48-hour cycle. Length of hospital stay, days from surgery to discharge, days from start of NPWT to discharge, clinical improvement, and safety. RESULTS: Four patients were diagnosed with PC between 2 and 5 days of evolution. Two diabetic adults developed the condition secondary to trauma, the adolescent as a result of a cosmetic piercing, and the infant associated to sinusitis. NPWT reached -125 mm·Hg, except for the infant who received -75 mm·Hg. The average number of days necessary for improvement with NPWT was 6.7 days. Only 2 patients required surgical reconstruction. Time from debridement to discharge was in average 13.5 days. No ocular complications were observed, and follow up was satisfactory with normal eyelid function and aesthetics and preserved visual acuity. CONCLUSIONS: NPWT proved to be safe and effective for treating locally complicated PC as an adjuvant therapy to antibiotic and surgical treatment that decreased the length of hospital stay, and the time for recovery in patients that were slow responders. No ocular complications were observed in any of these patients' follow up ranging from 1 to 4 years.

Infectious Complication Following Midface Reconstruction With Calcified Triglyceride.

This case report describes an infectious complication related to the use of calcified triglyceride (Kryptonite Bone Cement) in post-traumatic midface reconstruction. Ultimately, the infected material required removal, and the facial deformity was repaired with subsequent procedures. The literature suggests that bone cement products should be used with caution when in contact with the paranasal sinuses.

Complementary treatment of contact lens-induced corneal ulcer using honey: a case report.

The aim of this study was to report the complementary use of honey for treatment of a contact lens-induced corneal ulcer. A 23-year-old contact lens user presented with a corneal ulcer in her left eye. She had visual acuity reduced to hand movement. There was a history of wearing contact lenses while swimming in a lake seven days before presentation. The cultures from corneal scrapings and contact lenses were positive for Klebsiella oxytoca, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Pseudomonas spp. The treatment with topical levofloxacin and 25% (w/v) γ-irradiated honeydew honey solution was effective and the patient achieved final best corrected visual acuity of affected eye. In addition to positive clinical outcome, honeydew honey was shown to be highly effective in vitro against ocular isolates, in particular S. maltophilia. The minimal inhibitory concentrations for honeydew honey ranged from 5% to 10%. These results demonstrate that honey is a promising antibacterial agent in management of corneal ulcers. Moreover, honey exhibits anti-biofilm and anti-inflammatory properties, and thus becomes an interesting ophthalmologic agent.

The use of topical honey in the treatment of corneal abrasions and endotoxin-induced keratitis in an animal model.

PURPOSE: To investigate the effect of topically applied honey on intact corneas, surgically induced corneal abrasions and endotoxin induced keratitis. MATERIALS AND METHODS: The effect of honey on the cornea was investigated by application of honey on intact corneas, wounded corneas and endotoxin-induced keratitis in Lewis rats. The corneas were wounded by creating an epithelial defect using a surgical blade, and the keratitis was induced by topically applying Pseudomonas aeruginosa endotoxin to scarified corneas. After treatment rats were sacrificed and cornea harvested in each case. Corneas were processed for paraffin embedding for histological and immuno-fluorescence staining. Corneas were also harvested and processed for total ribonucleic acid (RNA) isolation for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for various growth factors and inflammatory chemokines/cytokines). RESULTS: Histological analysis revealed that no inflammation or morphological changes occurred after honey treatment in naive intact corneas. Vascular endothelial growth factor (VEGF) levels were also not altered after honey treatment. Topical application of honey to injured corneas resulted in faster epithelial healing and decreased expression of VEGF, transforming growth factor beta (TGF-ß), interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF-α) in injured corneas. Our results also established that honey treatment reduced the inflammation in endotoxin-induced keratitis by reducing the levels of angiogenic factors (VEGF and TGF-ß), inflammatory cytokines (IL-12) and chemokines (CC chemokine receptor 5(CCR-5)). CONCLUSION: Short term use of honey on intact corneas can be safe. Honey has anti-angiogenic and anti-inflammatory properties that can be explored in several corneal inflammatory and infectious conditions.

The potential of phage therapy in bacterial infections of the eye.

Antibiotic resistance has become a major health challenge which poses a significant threat, also in ophthalmology. For example, methicillin-resistant Staphylococcus aureus may cause dramatic complications, including bilateral blindness as a consequence of orbital cellulitis and panophthalmitis. This menace has provoked a greatly revived interest in phage therapy. In recent years, a number of papers have been published suggesting its efficacy in animal and human bacterial infections, but none of them addressed the phage potential in ophthalmology, which is the subject of this mini review.

Heat treatment enhances healing process of experimental pseudomonas corneal ulcer.

We investigated the effects of hyperthermia on the healing process of experimental Pseudomonas corneal ulceration (PCU). Hartley guinea pigs were used to develop animal models of PCU. As a heat source, disposable chemical pocket warmers were applied. The healing process of PCU was compared between the heat-treated corneas and the control corneas. The severity of infection and the degree of angiogenesis were classified by a clinical scoring system. The animals were euthanized 14 days after infection and the corneas were submitted for histopathological examination. The expression of vascular endothelial growth factor (VEGF) was examined immunohistochemically. Comparative reverse transcription polymerase chain reaction was performed to measure the expression level of VEGF in the cornea. Hyperthermia significantly promoted corneal epithelization and neovascularization in the PCU model. Heat treatment significantly decreased the number of viable Pseudomonas organisms present in PCU. On immunohistochemistry, the heated cornea demonstrated more intense staining for VEGF. Comparative reverse transcription polymerase chain reaction showed upregulation of the expression level of VEGF mRNA in the heat-treated cornea. Hyperthermia accelerated the healing process of PCU with increased corneal neovascularization. Angiogenesis may play an important role in the PCU healing process, which is enhanced by the heat treatment.

Postoperative infection with group A beta-hemolytic Streptococcus after blepharoplasty.

PURPOSE: To report a case of group A beta-hemolytic streptococcal infection with signs of early necrotizing fasciitis after cosmetic blepharoplasty in a healthy patient. DESIGN: Interventional case report. METHODS: A healthy 59-year-old woman underwent outpatient bilateral upper and lower blepharoplasty with midface lifting. Thirty hours postoperatively she developed marked pain and edema of the left eyelids and face, and a violaceous eyelid bulla, which heralded early necrotizing fasciitis. Culture of the serosanguinous exudates from the left eyelid revealed group A beta-hemolytic Streptococcus organisms. RESULTS: The patient was treated with intravenous antibiotics, intravenous corticosteroids, hyperbaric oxygen therapy, and wound debridement. The infection resolved with mild cicatrization of the left upper eyelid. CONCLUSIONS: Group A beta-hemolytic Streptococcus is an increasingly recognized cause of infection that occurs after trauma or surgery, even in highly vascularized areas such as the eyelids and face. It is a potentially devastating infection, particularly in vascularly compromised patients, and requires immediate and aggressive treatment.