Infectious keratitis: A review.

Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface disease. Staphylococcus species, Pseudomonas aeruginosa, Fusarium species, Candida species and Acanthamoeba species are the most common causal organisms. Culture of corneal scrapes is the preferred initial test to identify the culprit organism. Polymerase chain reaction (PCR) tests and in vivo confocal microscopy can complement the diagnosis. Empiric therapy is typically commenced with fluoroquinolones, or fortified antibiotics for bacterial keratitis; topical natamycin for fungal keratitis; and polyhexamethylene biguanide or chlorhexidine for acanthamoeba keratitis. Herpes simplex keratitis is mainly diagnosed clinically; however, PCR can also be used to confirm the initial diagnosis and in atypical cases. Antivirals and topical corticosteroids are indicated depending on the corneal layer infected. Vision impairment, blindness and even loss of the eye can occur with a delay in diagnosis and inappropriate antimicrobial therapy.

Statins in Neuro-ophthalmology.

Statins are effective and well-tolerated hypolipidaemic agents which have been increasingly studied for their pleiotropic immunomodulatory and anti-inflammatory effects. Statins have potential therapeutic benefit in a range of neuro-ophthalmological conditions but may also induce or exacerbate certain neurological disorders. This literature review examines evidence from clinical and in vitro studies assessing the effects of statins in myasthenia gravis, myopathy, multiple sclerosis, neuromyelitis optica, idiopathic intracranial hypertension (pseudotumour cerebri), migraine, giant cell arteritis, Bell's palsy, ocular ischaemia, stroke, Alzheimer's disease and Parkinson's disease.

Microbial keratitis in Sydney, Australia: risk factors, patient outcomes, and seasonal variation.

PURPOSE: To provide recent data on patient demographics, clinical profile and outcomes of patients with microbial keratitis over a 5-year period at the Sydney Eye Hospital, and to identify seasonal variations of the main causative organisms. METHOD: A retrospective study of patients with a clinical diagnosis of microbial keratitis and corneal scrape performed between 1 January 2012 and 31 December 2016. Clinical information was gathered from medical records and pathology data. RESULTS: One thousand fifty-two eyes from 979 patients with a mean age of 54.7 ± 21.5 years (range 18-100 years) were included. The majority of cases were bacterial (65%) followed by polymicrobial (2.4%), fungi (2.3%), and culture-negative (31%). Common risk factors for microbial keratitis were contact lens wear (63%) and previous topical steroid use (24%). Factors significantly associated with poor patient outcomes in the multivariate model were age, visual acuity, and epithelial defect size (p < 0.05). Patients with fungal or polymicrobial keratitis presented with worse clinical features at initial and final presentation (p < 0.05). There was a significant variation in the occurrence of Pseudomonas aeruginosa (p = 0.018) and fungal keratitis (predominately made up of Candida and Fusarium species) (p = 0.056) in the hottest seasons. CONCLUSION: Poorer outcomes are more likely to be seen in older patients and those presenting with poor visual acuity and large epithelial defects at the initial presentation.

The clinical and microbiological features and outcomes of fungal keratitis over 9 years in Sydney, Australia.

To describe the clinical features, management and outcomes in patients with fungal keratitis at the Sydney Eye Hospital, Australia, over a 9-year period to guide appropriate initial therapy. A retrospective case review was conducted. Patients diagnosed with fungal keratitis from 1 January 2009 to 31 December 2017 were identified from hospital coding and pathology databases. Data were extracted from the medical records. A total of 55 episodes from 51 patients were included. Mean age was 60 ± 20 years (range: 19-91 years), and 33 were male. The fungal species was not identified in two patients. Predisposing factors included ocular surface disease in 17 eyes (32%); corneal disease, 15 (28%); corneal trauma, 12 (23%); and contact lens wear, 13 (24.5%). Fusarium spp. (15, 27%) and Candida parapsilosis (10, 18%) were the most common isolates. The median visual acuity at presentation was 1.3 logMAR (range: 0 to 3) and after treatment 0.7 logMAR (range: -0.02 to 3) (P = .008). Despite medical therapy, most commonly with natamycin and topical and oral voriconazole, surgical intervention was required in 21 eyes (40%); including antifungal injections in 9 (16%); corneal transplantation, 16 (30%); evisceration, 2 (4%); and enucleation, 1 (2%). A poor visual outcome was recorded in 27 of 43 (63%) patients. Fungal keratitis remains a cause of significant ocular morbidity; the majority of patients face a poor outcome despite intense medical and at times surgical treatment. In our setting, fungal keratitis was more commonly associated with corneal or ocular surface disease.

Antimicrobial resistance trends in bacterial keratitis over 5 years in Sydney, Australia.

IMPORTANCE: Antimicrobial resistance (AMR) patterns in bacterial keratitis may fluctuate in a geographic location over time. BACKGROUND: To investigate any change in AMR patterns in Sydney, Australia. DESIGN: Retrospective case series. PARTICIPANTS: All patients with microbial keratitis who underwent a corneal scrape and culture from 2012 to 2016 at the Sydney Eye Hospital. METHODS: Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry identified organisms. The Calibrated Dichotomous Susceptibility method determined antibiotic susceptibilities. MAIN OUTCOME MEASURES: Isolated organisms and antibiotic susceptibilities. RESULTS: There were 1084 corneal scrapes from 957 patients. The mean age was 54 years (range 18-100) and 52% were male. Cultures were positive in 711 of 1084 scrapes (66%), with 884 organisms identified. Of the bacteria isolated, 685 of 884 (78%) were Gram-positive and 199 of 884 (22%) were Gram-negative. Overall, the most common bacteria were coagulase-negative Staphylococci (CoNS) (405/884, 46%). Methicillin-resistance was detected in 7% of Staphylococcus aureus isolates (7/103). Methicillin-resistance in CoNS (ie, also cefalotin resistance) was reported in 19% of isolates and ciprofloxacin 8%. For methicillin-sensitive S aureus (MSSA), 5% of isolates were resistant to ciprofloxacin. For Corynebacterium spp., 34% of isolates were resistant to chloramphenicol and 9% to ciprofloxacin. The most common Gram-negative bacteria was Pseudomonas aeruginosa (109/199, 55%). One case was resistant to ciprofloxacin. CONCLUSIONS AND RELEVANCE: Coagulase-negative staphylococcal species were the most frequently suspected of causing bacterial keratitis. Increased resistance to cefalotin was identified for CoNS and to ciprofloxacin for Corynebacterium spp., MSSA and P aeruginosa compared to a previous study in Sydney in 2002 to 2003.

Effectiveness of pharmaceutical interventions for meibomian gland dysfunction: An evidence-based review of clinical trials.

Meibomian gland dysfunction is one of the most common ocular disorders encountered by ophthalmologists and is the leading cause of evaporative dry eye. The disease causes significant morbidity in the population such that patients seek treatment. Multiple clinical studies on pharmacological and mechanical interventions for the treatment of meibomian gland dysfunction have been evaluated. However, there is limited comparative clinical evidence for the effectiveness of these interventions. This review paper aims to report the clinical evidence for pharmaceutical interventions for meibomian gland dysfunction in order to guide clinicians in the management of the disease.

Keratitis antimicrobial resistance surveillance program, Sydney, Australia: 2016 Annual Report.

IMPORTANCE: Antimicrobial resistance data from bacterial keratitis in Australia are lacking. BACKGROUND: Antimicrobial resistance is a global health threat. Bacterial keratitis is an ophthalmic emergency requiring immediate and effective treatment. DESIGN: Retrospective cohort study of bacterial isolates and antibiotic susceptibility profiles at a quaternary hospital in Sydney, Australia. PARTICIPANTS: Two hundred and twenty-four corneal scrapes from patients from January 1 to December 31, 2016. METHODS: Matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry identified bacteria. The Calibrated Dichotomous Sensitivity (CDS) method determined antibiotic susceptibilities. MAIN OUTCOME MEASURES: Isolated organisms and antibiotic susceptibilities. RESULTS: One hundred and sixty-eight scrapes of 224 (75%) were culture positive. One hundred and thirty-one patients had a single organism isolated and 21 had mixed bacterial growth. Of the 157 organisms isolated, 131 (83%) were Gram-positive and 27 (17%) Gram-negative. Of the Gram-positive organisms, 75 (57%) were coagulase-negative Staphylococci (CoNS), 15 (11%) Staphylococcus aureus (including one methicillin-resistant Staphylococcus aureus [MRSA]) and 8 (6%) Corynebacterium spp. Of the Gram-negative organisms, 15 (58%) were Pseudomonas aeruginosa. With methicillin-sensitive Staphylococcus aureus (MSSA) resistance to chloramphenicol was 21%, ciprofloxacin 7% and gentamicin 7%. With CoNS resistance to cefalotin was 9%, gentamicin 9% and ciprofloxacin 9%. With Corynebacterium spp. resistance was 40% to cefalotin, chloramphenicol 25% and ciprofloxacin 14%. CONCLUSIONS AND RELEVANCE: Staphyloccocus spp. and Pseudomonas spp. were the most common microorganisms isolated. There was low resistance to cefalotin and ciprofloxacin for these isolates. More than 90% of these would be covered by current therapeutic recommendations for empiric therapy in Australia.

Vinpocetine protects inner retinal neurons with functional NMDA glutamate receptors against retinal ischemia.

Retinal ischemia is involved in the pathogenesis of many major vision threatening diseases. Vinpocetine is a natural drug, which has a range of neuroprotective actions against retinal ischemia including modulating cation flow, improving metabolic activity and preventing apoptosis. The exact mechanism behind these actions remains unknown but may involve glutamate receptors, major components of the ischemic cascade. This study examined the effects of vinpocetine in association with specific ionotropic glutamate receptor agonists: N-methyl-D-aspartate (NMDA) and kainate. Vinpocetine's actions to improve cation channel permeability and cell marker immunoreactivity following ischemia appeared to be limited to NMDA activation with no changes observed following kainate stimulation. Vinpocetine's actions were lost in the presence of an NMDA receptor inhibitor further suggesting they may be secondary to NMDA receptor activation. NMDA receptor function was also necessary for vinpocetine's actions on glucose availability during ischemia but not lactate dehydrogenase (LDH) activity in the ischemic retina suggesting not all of vinpocetine's actions are linked to NMDA receptor function. These results may explain vinpocetine's effectiveness as a neuroprotective agent as the NMDA receptor is implicated in the pathogenesis of ischemia in a range of tissues of the central nervous system.

Corneal biopsy for diagnosis of recalcitrant microbial keratitis.

PURPOSE: To document the findings of corneal biopsies for progressive microbial keratitis in a large tertiary referral institution. METHODS: A retrospective medical records review of all patients who underwent at least one corneal biopsy for the diagnosis of microbial keratitis at Sydney Eye Hospital, Australia between January 1, 2010 and December 31, 2016 was performed. RESULTS: Thirty-eight patients (18 men and 20 women) underwent a corneal biopsy for progressive microbial keratitis unresponsive to broad-spectrum topical antimicrobials. Risk factors for microbial keratitis included contact lens wear in 8 (21%), recent intraocular surgery in 5 cases (13%), recent agricultural trauma in 3 cases (8%), exposure keratopathy due to Graves' orbitopathy in 1 case (3%), and profound systemic immunosuppression due to chemotherapy for leukaemia in 1 case (3%). The remaining 20 patients had no identifiable risk factors. Fifteen patients (39%) had a positive biopsy result, which identified bacteria in 6 cases and Mycobacteria in 1 case, both by culture of the biopsy specimen. Three cases of fungus were identified on culture of biopsy specimen, two of which were also confirmed on histopathology and an additional case was identified from histopathology alone. A single case of Acanthamoeba was diagnosed by culture and histopathology, and an additional 3 cases were diagnosed on histopathology alone. A corneal biopsy yielded new organisms in 73% (11/15) cases where the culture results of biopsy specimens were positive. CONCLUSION: Corneal biopsy is an important tool in the diagnosis of progressive keratitis, often identifying causal organisms not found on corneal scraping alone.

Pre-treatment with vinpocetine protects against retinal ischemia.

Vinpocetine has been shown to have beneficial effects for tissues of the central nervous system subjected to ischemia and other related metabolic insults. We recently showed vinpocetine promotes glucose availability, prevents unregulated cation channel permeability and regulates glial reactivity when present during retinal ischemia. Less is known however about the ability of vinpocetine to protect against future ischemic insults. This study explores the effect of vinpocetine when used as a pre-treatment in an ex vivo model for retinal ischemia using cation channel permeability of agmatine (AGB) combined with immunohistochemistry as a measure for cell functionality. We found that vinpocetine pre-treatment reduced cation channel permeability and apoptotic marker immunoreactivity in the GCL and increased parvalbumin immunoreactivity of inner retinal neurons in the inner nuclear layer following ischemic insult. Vinpocetine pre-treatment also reduced Müller cell reactivity following ischemic insults of up to 120 min compared to untreated controls. Many of vinpocetine's effects however were transient in nature suggesting the drug can protect retinal neurons against future ischemic damage but may have limited long-term applications.

Presumed Microbial Keratitis Cases Resulting in Evisceration and Enucleation in Sydney, Australia.

PURPOSE: Describe presumed microbial keratitis cases resulting in evisceration/enucleation from 2012 to 2016 in Sydney, Australia. METHODS: A retrospective case review included 33 patients. Cases were identified from pathology and hospital coding data. Sociodemographic and clinical details were collated. RESULTS: Mean age was 79 years (range: 38-100 years), and 64% female. There were 30 eviscerations and 3 enucleations, at a median time of 8 days (range: 1-270 days) due to endophthalmitis (n = 15, 45%). Major ocular associated factors included topical corticosteroid use in 12 patients (36%), exposure keratopathy in 4 (12%), ectropion in 3 (9%), degenerative corneal disease in 3 (9%), and corneal graft in 2 (6%). Pseudomonas aeruginosa was the most common isolate with no reports of antimicrobial resistance. CONCLUSIONS: Educating elderly patients with a history of topical corticosteroid use, corneal or ocular surface disease about prompt hospital presentation and treatment of microbial keratitis may decrease the probability of losing the eye.

Outcomes of Microbial Keratitis Cases Resistant to Antimicrobials in Sydney, Australia.

PURPOSE: The purpose of this study was to describe demographics, predisposing factors, clinical features, treatment, and outcomes of microbial keratitis cases resistant to antimicrobials. METHODS: A retrospective case series was conducted. All patients with microbial keratitis resistant to antimicrobials who underwent a corneal scrape and culture from 2012 to December 2016 at the Sydney Eye Hospital were included. Cases were identified from pathology and hospital coding data. Coagulase-negative staphylococci (CoNS), Staphylococcus aureus (S. aureus), and Corynebacterium spp. resistant to cefalotin, chloramphenicol, ciprofloxacin, or gentamicin were analyzed. RESULTS: One hundred fifteen episodes had a resistant CoNS, 24 S. aureus, and 12 Corynebacterium spp. Antimicrobial resistance was associated with older women (67%, median age 83 years) with Corynebacterium spp. (P < 0.001), corneal graft, and previous topical steroid use. Larger epithelial defects (P = 0.203) and infiltrates (P = 0.180) were more likely to be associated with Corynebacterium spp., but not statistically significant. At the initial and final visits, resistant S. aureus (75% vs. 67%) and Corynebacterium spp. (78% vs. 80%) cases were more likely to be classified as blind (>3/60) compared with CoNS (45% vs. 28%) (P = 0.011 vs. P = 0.004). Corneal perforation occurred more often in resistant S. aureus cases (P < 0.001), whereas slow and nonhealing epithelial defects needing other procedures were more likely to occur with resistant Corynebacterium spp. (P < 0.001). CONCLUSIONS: Patients with resistant CoNS were younger and presented with smaller ulcers and moderate vision loss. Visual and clinical outcomes were significantly better for resistant CoNS than for those with resistant S. aureus or Corynebacterium spp.

Predisposing factors, microbiological features and outcomes of patients with clinical presumed concomitant microbial and herpes simplex keratitis.

BACKGROUND/OBJECTIVES: To describe the predisposing factors, pathogens and outcomes in patients with clinical presumed concomitant microbial and herpes simplex keratitis (HSK) at Sydney Eye Hospital, Australia over a 5-year period. SUBJECTS/METHODS: A retrospective case review was conducted. Patients with clinical presumed concomitant microbial and HSK from 2012 to 2016 were identified from pathology and hospital coding databases. Data were extracted from the medical records. VA was converted to the logarithm of the minimum angle of resolution (logMAR). 'Poor' outcome was defined as final VA worse than 6/60, or decrease in VA during treatment, or presence of complication, or needed surgical intervention. RESULTS: 126 episodes in 121 patients were included; median age 70 years (range 18-96); 56% male. Predisposing factors included blepharitis 20/126 (16%) cases, and corneal transplantation 19 (15%). Forty-six (37%) cases had prior HSK. Coagulase-negative staphylococci 51/116 (44%), Staphylococcus aureus 11 (9%), and Pseudomonas aeruginosa 11 (9%) were the most common isolates. The median VA at initial visit was 1.7 logMAR (range 0.04-2.7) and at final visit, 0.98 logMAR (range 0-2.7) (P < 0.05). Complications occurred in 70 episodes: persistent epithelial defect in 38 (30%); intraocular pressure elevation in 15 (12%), and corneal perforation in 12 (10%). 'Poor' outcome was recorded in 46/75 (61%) episodes. CONCLUSIONS: Patients with clinical presumed concomitant microbial and HSK face significant ocular morbidity and poor visual outcome. In our setting, previous HSK, corneal and ocular surface disease, were common predisposing factors and Gram-positive bacteria were the most commonly associated organisms.

Dry eye signs and symptoms in patients on aromatase inhibitor therapy.

PURPOSE: The study aimed to test whether symptomatic dry eye in aromatase inhibitor (AI) patients is associated with the clinical features of evaporative dry eye. METHODS: A cross-sectional, observational study of postmenopausal women treated with AI was conducted. Clinical information was gathered from their treating clinician. Ocular and treatment symptoms were assessed using validated questionnaires. Clinical assessments were performed to assess for dry eye. The primary outcome measure for this study was dry eye symptoms measured via questionnaire. The secondary outcome measures were clinical signs of dry eye and hormone levels. RESULTS: A total of 25 women on AI were recruited. 64% of women reported symptoms of dry eye (ocular surface disease index ≥ 13). Higher tear osmolarity (323 vs 307 mOsm/L, p = 0.002) and increased meibomian gland dropout (4 vs 1, p = 0.002) were observed in patients with symptomatic dry eye when compared to asymptomatic patients. Multivariate logistic regression identified that longer duration of AI use and higher tear osmolarity increased the likelihood of a patient experiencing dry eye symptoms. CONCLUSION: Our study found increased tear osmolarity and meibomian gland drop out in women on AI with symptomatic dry eye. Longer duration of AI therapy and higher tear osmolarity may increase the risk of developing dry eye.

Clinical Registries in Dry Eye Disease: A Systematic Review.

PURPOSE: The objective of this study was to undertake a systematic review of the literature reporting on clinical registries in dry eye disease (DED). METHODS: Electronic searches were conducted using systematic review methodology to provide an overview of clinical registries in ophthalmology and to identify clinical registries reporting on dry eye parameters. Two reviewers independently assessed titles and abstracts, then full-texts for eligibility. RESULTS: A total of 129 clinical registries in ophthalmology were identified. The most common conditions captured were blindness or low vision, followed by glaucoma and corneal transplantation. Most of the registries originated in Europe (n = 56), followed by North America (n = 28). Of the registries identified, 12 were multinational, 59 were national, and 17 were regional. The second search identified 27 eligible articles, from which 8 clinical registries reporting on dry eye parameters were identified. One registry included patients with a diagnosis of dry eye. The remaining 7 registries included patients from a nationwide administrative ophthalmic database (n = 1), Sjögren syndrome (n = 4), glaucoma (n = 1), or were monozygotic and dizygotic twins (n = 1), who were evaluated for DED. Five of the registries were actively collecting data. CONCLUSIONS: Most of the registries identified in this review evaluated aqueous deficient dry eye; however, the most common type of dry eye in the general population is evaporative. Few registries also collected recommended dry eye clinical assessment. A well-designed clinical registry for DED that engages international eye care clinicians has the potential to vastly contribute to addressing pivotal gaps in understanding this highly prevalent disease.

Microbial Keratitis After Corneal Collagen Cross-Linking for Corneal Ectasia.

PURPOSE: The aim of this study was to report the clinical profile and microbiological of patients with microbial keratitis post accelerated corneal collagen cross-linking (CXL). METHODS: A retrospective case series of all patients diagnosed with microbial keratitis post-CXL who attended the Sydney Eye Hospital, Australia from January 1, 2012 to December 31, 2019 were included. Patients were identified from hospital coding and pathology data. Data were extracted from patients' medical records. RESULTS: Eleven eyes from 10 patients with a mean age of 29 ±â€Š11 years (range 16-48) were included. The median time of infection after CXL surgery was 4 days [interquartile range (IQR) 3-83]. Median initial and final Visual acuity at presentation were 1.3 logMAR (IQR 1-2.0) and 0.8 logMAR (IQR 0.6-1.2), respectively. The culture positivity rate was 92%, identifying 13 isolates, predominately made up of coagulase-negative Staphylococcus (n = 6, 50%) and Staphylococcus aureus (n = 3, 25%). The median epithelial healing time was 30 days (IQR 15-53). CONCLUSIONS: Post-CXL microbial keratitis was predominately associated with gram-positive bacteria and in some cases delayed epithelialization. Microbial keratitis post-CXL may lead to moderate to poor patient outcomes.

Late onset of microbial keratitis after laser in situ keratomileusis surgery: case series.

PURPOSE: To report predisposing factors, clinical features, microbiology spectrum, antibiotic resistance, antimicrobial therapy, and outcomes of patients with a previous laser in situ keratomileusis (LASIK) surgery and diagnosed with presumed microbial keratitis. SETTING: Sydney Eye Hospital, Sydney, New South Wales, Australia. DESIGN: Retrospective case review. METHODS: Patients were identified from pathology and hospital coding data from 2012 to 2016. Inclusion criteria were all patients with a previous LASIK surgery, a presumed diagnosis of microbial keratitis, and a corneal scrape performed and aged older than 18 years. Demographics, clinical details, and outcomes were collated from the medical records. RESULTS: Sixteen patients were included, with median age of 41.5 years (range 22 to 85 years) and 56.2% of women. The median time between LASIK procedure and microbial keratitis presentation was 38.3 months (interquartile range 6.7 to 77.45 months). Cultures were positive for bacteria in 12 (75%) of 16 scrapes. Of the bacterial isolates, 12 (85.7%) were gram-positive and 2 (14.3%) gram-negative. Sensitivity profiles for the isolated bacteria were similar between fortified antibiotics (cefalotin and gentamicin) and commercial products (chloramphenicol and ofloxacin). Complications included the need for tectonic grafts, nonhealing epithelial defects, thinning, and neovascularization. CONCLUSIONS: Late onset of keratitis after LASIK can occur with no positive cultures for nontuberculous mycobacteria, no interface involvement, and no other usual features reported in case series of infectious keratitis in LASIK patients. It has a similar clinical course to non-LASIK keratitis, such that the surgery may not have been a risk factor for infection.

Topical Steroids as Adjunctive Therapy for Bacterial Keratitis: Evidence From a Retrospective Case Series of 313 Cases.

PURPOSE: The aim of this study was to report topical steroid usage in bacterial keratitis and analyze the effects of steroids on patients' outcomes to the main causative organisms. DESIGN: A retrospective case-series. METHODS: This study included all patients with corneal scrape positive bacterial keratitis from January 2012 to December 2016 at the Sydney Eye Hospital, Sydney, Australia. Cases were identified from pathology results and hospital coding, and data collected from medical records. RESULTS: A total of 313 eyes from 308 patients with a mean age of 51 years [interquartile range (IQR) 36-72] were included. Of these patients, 192 (61%) were treated with topical steroids. High-dose steroids were prescribed in 22 (11%) cases, regular-dose in 88 (46%), and low-dose in 82 (43%). The median time until the implementation of steroid use was 4 days (IQR 3-7). Patients prescribed with topical steroids had significantly longer healing times than the "no steroid" group (11 vs 6.5, P < 0.001). Patients with Pseudomonas aeruginosa keratitis and topical steroid use had worse clinical outcomes, with a higher proportion having longer healing times (P = 0.04) and corneal scarring (P = 0.02). CONCLUSIONS: Adjuvant topical steroid therapy did not affect visual acuity, patient outcomes or the rate of adverse effects but may delay epithelial healing in bacterial keratitis in these patients. Topical steroids may have a differential effect depending on the specific causative organisms; however, a clinical trial is needed to assess this.