Sarocladium and Acremonium infections: New faces of an old opportunistic fungus.

The genera Acremonium and Sarocladium comprise a high diversity of morphologically and genetically related fungi generally found in the environment, although a few species, mainly Sarocladium kiliense and Acremonium egyptiacum, can also be involved in many human infections. Clinical management of opportunistic infections caused by these fungi is very complex, since their correct identification is unreliable, and they generally show poor antifungal response. More than 300 clinical cases involving a broad range of Acremonium/Sarocladium infections have so far been published, and with this review we aim to compile and provide a detailed overview of the current knowledge on Acremonium/Sarocladium human infections in terms of presentation, diagnosis, treatments and prognoses. We also aim to summarise and discuss the data currently available on their antifungal susceptibility, emphasising the promising results obtained with voriconazole as well as their impact in terms of animal infections.

Unorthodox ophthalmic preparations on the Ghanaian market: a potential risk for ocular and enteric infections.

PURPOSE: Microbial contamination of orthodox ophthalmic preparations poses a serious threat to the user by causing ocular infections. There is no such information about unorthodox ophthalmic preparations in a medical pluralistic system such as Ghana. The aim of this study was to assess unorthodox ophthalmic medications on the Ghanaian market for possible microbial contaminations. METHODS: Unorthodox ophthalmic preparations were collected across different herbal and homeopathic outlets in Ghana. A total of 27 samples were collected from the ten (10) regions in Ghana. The samples were inoculated in different culture media (Plate count Agar, Blood Agar, MacConkey Agar, Saboraud Dextrose Agar). The microorganisms isolated were identified using standard microbiological procedures and antimicrobial susceptibility was done to determine whether they were resistant or susceptible strains. RESULTS: All the samples were contaminated with bacteria and the majority were contaminated with fungus. A total of forty-eight bacteria spp. was isolated thus seven different types namely: Staphylococcus aureus, Bacilli spp., Serrati spp., Escherichia coli, Pseudomonas spp., Klebsiella spp. and Shigella spp. with Staphylococcus aureus being the predominant bacteria. For fungi, a total of eleven fungi species thus four different types namely: Cephalosporium spp., Penicillium spp., Cercosporium spp. and Clasdosporium spp. with the predominant fungi being Penicillium spp. Per the class of preparations, 15 contaminants were isolated from ten (10) anti-inflammatory preparations. The fungi were all susceptible to both Ketoconazole and Fluconazole but the bacteria were resistant to all the conventional antibiotics except Ciprofloxacin and Gentamycin. CONCLUSION: Unorthodox ophthalmic preparations found on the Ghanaian market are contaminated with bacteria and fungi of clinical importance.

Rose Bengal Photodynamic Antimicrobial Therapy for Patients With Progressive Infectious Keratitis: A Pilot Clinical Study.

PURPOSE: To report clinical outcomes of rose bengal photodynamic antimicrobial therapy (RB-PDAT) as an adjunct treatment for severe, progressive infectious keratitis. DESIGN: Consecutive interventional case series. METHODS: Patients with progressive infectious keratitis unresponsive to standard medical therapy underwent RB-PDAT at the Bascom Palmer Eye Institute from January 2016 through March 2018. RB-PDAT was performed by applying a solution of rose bengal (0.1% or 0.2% RB in balanced salt solution) to the de-epithelialized cornea for 30 minutes, followed by irradiation with a 6 mW/cm2 custom-made green LED source for 15 minutes (5.4 J/cm2). RESULTS: The current study included 18 patients (7 male and 11 female) ranging from 17 to 83 years old. Acanthamoeba was the most frequent microbe (10/17; 59%), followed by Fusarium spp. (4/17; 24%), Pseudomonas aeruginosa (2/17; 12%), and Curvularia spp. (1/17; 6%); 1 patient had no confirmed microbiologic diagnosis. Main clinical risk factor for keratitis included contact lens wear (79%). The average area of epithelial defect prior to first RB-PDAT was 32 ± 27 mm2 and average stromal depth hyperreflectivity measured with anterior segment optical coherence tomography was 269 ± 75 µm. Successful RB-PDAT (avoidance of therapeutic keratoplasty) was achieved in 72% of the cases, with an average time to clinical resolution (decreased pain and inflammation with re-epithelialization and infiltrate resolution) of 46.9 ± 26.4 days after RB-PDAT. Time of follow-up after RB-PDAT was 13.3 ± 5.7 months. CONCLUSION: RB-PDAT can be considered as an adjunct therapy for cases of severe, progressive infectious keratitis before performing a therapeutic keratoplasty.

Efficacy of T-2307, a novel arylamidine, against ocular complications of disseminated candidiasis in mice.

OBJECTIVES: T-2307, a novel arylamidine, shows broad-spectrum activity against pathogenic fungi, including Candida albicans. Ocular candidiasis is one of the serious complications associated with Candida bloodstream infection and is known to be refractory to conventional antifungal agents. The aim of the present study was to clarify the effectiveness of T-2307 against ocular candidiasis using a mouse model. METHODS: We evaluated ocular fungal burden in mice infected with C. albicans that received treatment with antifungal agents [T-2307, liposomal amphotericin B (LAMB) or fluconazole] for 3 consecutive days. We also assessed survival rates of mice after C. albicans infection followed by treatment for 7 consecutive days. In addition, ocular T-2307 concentrations and in vitro effectiveness against C. albicans biofilm formation were evaluated. RESULTS: The ocular fungal burdens were significantly reduced after T-2307 treatment compared with the control group (no treatment received) and were comparable with those observed following treatment with LAMB or fluconazole in both early- and late-phase treatment experiments. In addition, all of the mice treated with antifungal agents survived for 3 weeks after infection, whereas mice in the control group died within 3 days. The ocular T-2307 trough concentration was maintained above the MIC in the infected mice. An in vitro biofilm inhibition experiment showed that T-2307 suppressed C. albicans biofilm formation at the sub-MIC level, which was comparable with amphotericin B. CONCLUSIONS: Given these results in experimental disseminated candidiasis, T-2307 may be an effective treatment against the complication of ocular candidiasis.

Ocular infections caused by Candida species: Type of species, in vitro susceptibility and treatment outcome.

PURPOSE: To report clinical and microbiological profile of patients with ocular candidiasis. MATERIALS AND METHODS: Patients with ocular candidiasis were retrospectively identified from microbiology records. Significant isolates of Candida species were identified by Vitek 2 compact system. Minimum inhibitory concentration (MIC) of antifungal agents such as amphotericin B, itraconazole, voriconazole, fluconazole and caspofungin was determined by E test and of natamycin by microbroth dilution assay. Data on treatment and outcome were collected from medical records. RESULTS: A total of 42 isolates of Candida were isolated from patients with keratitis-29, endophthalmitis-12 and orbital cellulitis-1. The most common species isolated was Candida albicans (12-keratitis, 4-endophthalmitis, 1-orbital cellulitis). All except one isolate were susceptible to amphotericin B. MIC of caspofungin was in the susceptible range in 28 (96.5%) corneal isolates while 12 out of 29 (41.3%) corneal isolates were sensitive to fluconazole. Resistance to voriconazole was seen in four corneal isolates. All isolates were susceptible to natamycin and all except two isolates were resistant or susceptible dose-dependent to itraconazole. Outcome of healed ulcer was achieved in 12/18 (66.6%) patients treated medically, while surgical intervention was required in 11 patients. Among the isolates from endophthalmitis patients, 11/12 were susceptible to amphotericin B, 6/12 to voriconazole and all to natamycin. Ten out of 11 patients (one patient required evisceration) with endophthalmitis were given intravitreal amphotericin B injection with variable outcome. CONCLUSIONS: Ocular candidiasis needs early and specific treatment for optimal results. Candida species continue to be susceptible to most commonly available antifungals including amphotericin B, voriconazole and natamycin.

Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the treatment of advanced infectious keratitis with corneal melting.

PURPOSE: To investigate the efficacy and safety of corneal collagen cross-linking (CXL) with photoactivated riboflavin (photoactivated chromophore for infectious keratitis [PACK]-CXL) in the management of infectious keratitis with corneal melting. DESIGN: Prospective clinical trial. PARTICIPANTS: Forty eyes from 40 patients with advanced infectious keratitis and coexisting corneal melting. METHODS: Twenty-one patients (21 eyes) underwent PACK-CXL treatment in addition to antimicrobial therapy. The control group consisted of 19 patients (19 eyes) who received only antimicrobial therapy. MAIN OUTCOME MEASURES: The slit-lamp characteristics of the corneal ulceration, corrected distance visual acuity, duration until healing, and complications were documented in each group. The Mann-Whitney U test was used for statistical analysis. P values less than 0.05 were considered statistically significant. RESULTS: The average time until healing was 39.76 ± 18.22 days in the PACK-CXL group and 46.05 ± 27.44 days in the control group (P = 0.68). After treatment and healing, corrected distance visual acuity was 1.64 ± 0.62 in the PACK-CXL group and 1.67 ± 0.48 in the control group (P = 0.68). The corneal ulceration's width and length was significantly bigger in the PACK-CXL group (P = 0.004 and P = 0.007). Three patients in the control group demonstrated corneal perforation; infection recurred in 1 of them. No serious complications occurred in the PACK-CXL group. CONCLUSIONS: Corneal CXL with photoactivated riboflavin did not shorten the time to corneal healing; however, the complication rate was 21% in the control group, whereas there was no incidence of corneal perforation or recurrence of the infection in the PACK-CXL group. These results indicate that PACK-CXL may be an effective adjuvant therapy in the management of severe infectious keratitis associated with corneal melting.

Pharmacological treatment for infectious corneal ulcers.

INTRODUCTION: Cornea ulceration and infectious keratitis are leading causes of corneal morbidity and blindness. Infectious causes are among the most frequent and most severe. Management strategies for bacterial corneal ulcers have changed significantly over the last decades, however with a more limited progress in the treatment and management of nonbacterial, infectious ulcers. AREAS COVERED: This paper provides an overview of the current principles, strategies and treatment choices for infectious corneal ulcers in adults. EXPERT OPINION: Topical application with a broad-spectrum antimicrobial remains the preferred method for the pharmacological management of infectious corneal ulcers. Increasing reports of clinical failures and in vitro resistance to antibiotics to treat the most common infectious (bacterial) corneal ulcers are increasing concerns. New approaches for improvement in the pharmacological management of corneal ulcers should focus on strategies for a more rational and evidence-based use of current antimicrobials and development of products to modulate the host immune response and to neutralize microbial toxins and other immune modulators.

[Optimization of complex treatment in ocular toxoplasmosis and concurrent infections].

137 patients (177 eyes) with verified toxoplasmic uveitis, retinitis, chorioretenitis were observed. Among them 65 patients had concurrent infections: tuberculosis, herpes simplex and chlamydia. Routine ophthalmologic, clinical and laboratory examination was performed. The results of intensive treatment in acute and chronic phases are presented, the staged drug pathogenic treatment including methods of specific therapy, based on differential approach to anti-inflammatory agents use, was provided. Early diagnosis and appropriate management including combined treatment of concurrent infections improves treatment efficacy and allows to achieve excellent results.

Photo-activated riboflavin therapy of refractory corneal ulcers.

PURPOSE: To evaluate the therapeutic effect of photo-activated riboflavin (PAR) for treating refractory corneal ulcers. METHODS: Seven eyes with infectious keratitis, presented with a gradually deteriorating, vision-threatening, corneal ulcer, despite intense antimicrobial therapy, were treated with PAR. The surgical procedure was deepithelialization of the affected corneas followed by UV-A riboflavin (B2) cross-linking. Local antimicrobial therapy was continued after the procedure. RESULTS: In all cases, the progression of corneal melting was halted after PAR treatment. Emergency keratoplasty was not necessary in any of the 7 eyes presented. More importantly, all the ulcers were healed without significant vascularization. CONCLUSION: PAR is a promising option for treating patients with therapy-refractory infectious keratitis to avoid emergency keratoplasty and should be considered as a potential adjuvant therapeutic tool in such eyes.

In vitro antimicrobial, anthelmintic and cyclooxygenase-inhibitory activities and phytochemical analysis of Leucosidea sericea.

ETHNOPHARMACOLOGICAL RELEVANCE: Leucosidea sericea is used as a vermifuge and in the treatment of ophthalmia by various tribes in southern African countries. AIM OF THE STUDY: The study aimed at screening leaves and stems of Leucosidea sericea for pharmacological activity and validating the plant's traditional use. A general phytochemical screening was also carried out. MATERIALS AND METHODS: Petroleum ether (PE), dichloromethane (DCM), ethanol (EtOH) and water extracts of the plant parts were investigated for antimicrobial, anthelmintic and cyclooxygenase (COX) inhibitory activities. Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) and Candida albicans were used for the antimicrobial evaluation. Caenorhabditis elegans was used for the anthelmintic assay using the microdilution technique. Cyclooxygenase-1 and -2 (COX-1 and -2) were used to evaluate the anti-inflammatory potential of the plant extracts. Phytochemical analysis for phenolic compounds, including gallotannins, condensed tannins and flavonoids was done using 50% methanol extracts of the leaves and stems employing spectrophotometric methods. RESULTS: The leaf extracts exhibited broad spectrum antibacterial activity ranging from 0.025 to 6.25mg/ml. The most noteworthy minimum inhibitory concentration (MIC) of 0.025 mg/ml was exhibited by PE and DCM leaf extracts against Bacillus subtilis and Staphylococcus aureus, respectively. In the anthelmintic assay, the best minimum lethal concentration (MLC) value of 0.26 mg/ml was observed for the DCM and EtOH leaf extracts. Both leaf and stem organic solvent extracts exhibited high to moderate inhibition against COX-1 and -2 at a screening concentration of 250 microg/ml. At lower concentrations, the extracts displayed a dose-dependent inhibition, with the lowest IC(50) values of 0.06 microg/ml (COX-1) and 12.66 microg/ml (COX-2) exhibited by the PE extract of the leaves. Generally, the leaf extracts exhibited better pharmacological activities and contained higher amounts of phenolic compounds than the stem extracts. Alkaloids and saponins were only detected in the leaf and stem extracts, respectively. CONCLUSION: The reported results support the local use of Leucosidea sericea against eye infections and as a vermifuge. The pharmacological activities exhibited by the leaf extracts are probably due to their higher phenolic levels.

Effects of dietary lysine supplementation on upper respiratory and ocular disease and detection of infectious organisms in cats within an animal shelter.

OBJECTIVE: To determine within a cat shelter effects of dietary lysine supplementation on nasal and ocular disease and detection of nucleic acids of Chlamydophila felis, feline calicivirus (FCV), and feline herpesvirus (FHV-1). ANIMALS: 261 adult cats. PROCEDURES: Cats were fed a diet containing 1.7% (basal diet; control cats) or 5.7% (supplemented diet; treated cats) lysine for 4 weeks. Plasma concentrations of lysine and arginine were assessed at the beginning (baseline) and end of the study. Three times a week, cats were assigned a clinical score based on evidence of nasal and ocular disease. Conjunctival and oropharyngeal swab specimens were tested for FHV-1, FCV, and C felis nucleic acids once a week. RESULTS: Data were collected from 123, 74, 59, and 47 cats during study weeks 1, 2, 3, and 4, respectively. By study end, plasma lysine concentration in treated cats was greater than that in control cats and had increased from baseline. There was no difference between dietary groups in the proportion of cats developing mild disease. However, more treated cats than control cats developed moderate to severe disease during week 4. During week 2, FHV-1 DNA was detected more commonly in swab specimens from treated versus control cats. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary lysine supplementation in the amount used in our study was not a successful means of controlling infectious upper respiratory disease within a cat shelter. Rather, it led to increases in disease severity and the incidence of detection of FHV-1 DNA in oropharyngeal or conjunctival mucosal swab specimens at certain time points.

Investigative modalities in infectious keratitis.

Standard recommended guidelines for diagnosis of infectious keratitis do exist. Based on an extensive Medline literature search, the various investigative modalities available for aiding the diagnosis of microbial keratitis have been reviewed and described briefly. Preferred practice patterns have been outlined and the importance of routine pre-treatment cultures in the primary management of infectious keratitis has been highlighted. Corneal scraping, tear samples and corneal biopsy are few of the specimens needed to carry out the investigative procedures for diagnosis and for initiating therapy in cases of microbial keratitis. In bacterial, fungal and amoebic keratitis, microscopic examination of smears is essential for rapid diagnosis. Potassium hydroxide (KOH) wet mount, Gram's stain and Giemsa stain are widely used and are important for clinicians to start empirical therapy before microbial culture results are available. The usefulness of performing corneal cultures in all cases of suspected infectious keratitis has been well established. In cases of suspected viral keratitis, therapy can be initiated on clinical judgment alone. If a viral culture is needed, scrapings should directly be inoculated into the viral transport media. In vivo confocal microscopy is a useful adjunct to slit lamp bio-microscopy for supplementing diagnosis in most cases and establishing early diagnosis in many cases of non-responding fungal and amoebic keratitis. This is a non-invasive, high resolution technique which allows rapid detection of Acanthamoeba cysts and trophozoites and fungal hyphae in the cornea long before laboratory cultures give conclusive results. Other new modalities for detection of microbial keratitis include molecular diagnostic techniques like polymerase chain reaction, and genetic finger printing by pulsed field gel electrophoresis.

Safety of prophylactic intracameral moxifloxacin 0.5% ophthalmic solution in cataract surgery patients.

PURPOSE: To determine the safety of prophylactic intracameral moxifloxacin 0.5% ophthalmic solution (Vigamox) in patients having cataract surgery. SETTING: American Eye Center, Manila, Philippines. METHODS: Preoperative and 1-month postoperative anterior chamber reaction, corneal endothelial cell density, and corneal thickness were assessed in 65 eyes that had cataract surgery with intracameral moxifloxacin. All eyes received 0.1 mL intracameral moxifloxacin 0.5% ophthalmic solution containing 500 mug of moxifloxacin as the last step of phacoemulsification. Different ophthalmologists conducted the postoperative evaluation in an observer-masked fashion. A P value less than 0.05 was considered significant. RESULTS: All 65 eyes completed the study. The mean age was 69.5 years +/- 9.13 (SD) (range 48 to 84 years). All eyes had a postoperative best corrected visual acuity of 20/30 or better. All eyes had trace to +2 cells and flare anterior chamber reaction only on the first day after surgery. The mean endothelial cell count was 2491.52 cells/mm(2) preoperatively and 2421.58 cells/mm(2) postoperatively. The mean difference was 70 cells/mm(2), which not statistically significant (P = .737). The increase of 17.80 microm in postoperative pachymetry 1 month after surgery was not statistically significant (P>.65). CONCLUSION: Intracameral Vigamox 0.5 mg/mL appeared to be nontoxic in terms of visual rehabilitation, anterior chamber reaction, pachymetry, and corneal endothelial cell density.

Impact of prior therapy on the recovery and frequency of corneal pathogens.

OBJECTIVE: To document the impact of prior antibiotic therapy on the recovery of corneal pathogens. METHODS: Medical records and laboratory reports of 334 consecutive microbial keratitis patients examined from January to December 2000 were reviewed. Comparisons of pathogens, culture positive rate, recovery time, antibiotic sensitivity profile, delay in presentation, and final visual acuity were analyzed for patients treated before presentation and those who were not. The chi square test was used to determine statistical significance. RESULTS: Of the 334 patients, 56% were exposed to at least one course of topical antimicrobials before culture. Patients on therapy were only slightly more likely to be culture negative (P = 0.317) but significantly more likely to have a delay in pathogen recovery (P = 0.002). Patients given prior antibiotics took significantly longer to heal (P = 0.003). Gram-negative organisms (47.5%) were the most frequent pathogens isolated from all culture-positive patients, followed by gram positives (28.7%), fungi (15.8%), and parasites (2%). An increase and significant difference in the frequency of fungi (P = 0.000) and acanthamoeba was reserved for the pretreated group. Gram negative organisms were more often isolated from patients who had not been pretreated (P = 0.002). Pretreated patients were more like to have a pathogen resistant to 1 or more of the commonly prescribed ocular antibiotics (P = 0.02). CONCLUSIONS: There is a delay in starting microbiologic-guided antibiotic treatment in patients who have received empiric therapy. Nonbacterial corneal pathogens may be associated more frequently with patients on prior therapy.