The Development of an Antimicrobial Contact Lens - From the Laboratory to the Clinic.

Contact lens wear is generally safe and provides excellent vision. However, contact lens wear is often associated with the risk of developing ocular surface infection and inflammation, and in severe cases, the infection can result in loss of vision. Antimicrobial peptide-coated contact lenses have been made to help reduce the incidence of infection and inflammation. This paper reviews the research progress from conception, through the laboratory and preclinical tests to the latest information on clinical testing of an antimicrobial contact lens. We provide insights into the pathways followed and pitfalls that have been encountered. The journey has not always been linear or smooth, but has resulted in some of the first published clinical testing of antimicrobial peptide-coated contact lenses in humans. We hope this may help lead to the development and commercialisation of antimicrobial contact lenses in the future.

[Uncommon mycoses]. / Micosis infrecuentes.

BACKGROUND: Fungal infections should be suspected in severe wounds that have been contaminated with organic material or soil, even when the patient is immunocompetent. The aim of this article is to contribute to a better understanding and knowledge of the antifungal sensitivity and epidemiology of some rare pathogens that may trigger severe infections. CASE REPORT: Four different moulds were isolated from the wounds of an immunocompetent woman who was involved in a road accident: Lichtheimia corymbifera, Scedosporium boydii, Fusarium solani and Purpureocillium lilacinum. Some of them were isolated from different sites. A profile of in vitro resistance was performed with an Epsilometer (Etest™) using five antifungal agents: voriconazole, posaconazole, itraconazole, anidulafungin an amphotericin B. The results obtained were consistent with those from other cases reported in the literature. CONCLUSIONS: Early aggressive surgery, antifungal therapy and, above all, frequent debridement of necrotic tissue, are the tools against filamentous fungi infections. Antifungal sensitivity of any mould involved in an infection has to be determined, in order to a better understanding of these rare pathogens whose incidence is increasing.

Infectious complications following probiotic ingestion: a potentially underestimated problem? A systematic review of reports and case series.

BACKGROUND: Little is studied about complications related to probiotic ingestion. This study proposes to present a synthesis and critical evaluation of the reports and series of cases on the infectious complications related to the ingestion of probiotics, which can raise awareness for the prescribing and use of probiotics for certain groups of patients. METHODS: Systematic review of reports and series of cases researched in the PubMed, SciELO and Scopus databases published until August 2018. The references of the articles were investigated manually for the search of cross references. SPSS version 23.0 was used for descriptive statistics and univariate analysis. RESULTS: We found 60 case reports and 7 case series, making up a total of 93 patients. Fungemia was the most common infectious complications with 35 (37.6%) cases. The genus Saccharomyces was the most frequent with 47 (50.6%) cases, followed by Lactobacillus, Bifidobacterium, Bacillus, Pedioccocus and Escherichia with 26 (27.9%), 12 (12.8%), 5 (5.4%), 2 (2.2%) and 1 (1.1%) case, respectively. Adults over 60 years of age, Clostridium difficile colitis, antibiotic use and Saccharomyces infections were associated with overall mortality. HIV infections, immunosuppressive drugs, solid organ transplantation, deep intravenous lines, enteral or parenteral nutrition were not associated with death. CONCLUSION: The use of probiotics cannot be considered risk-free and should be carefully evaluated for some patient groups. TRIAL REGISTRATION: CRD42016042289.

Early Enteral Feeding of Daikenchuto Stimulates Early Bowel Movement With Increased Portal Venous Blood Flow After Living Donor Liver Transplantation.

Daikenchuto (DKT), a Japanese Kampo medicine, had been reported to increase small intestinal blood flow after liver resection. The aim of this study was to evaluate the effects of early enteral feeding of DKT on portal venous flow and early bowel movement after living donor liver transplantation (LDLT) in an attempt to clarify whether these effects on bowel motility can prevent bacterial and/or fungal translocation. MATERIALS AND METHODS: Our prospective study included the consecutive 16 LDLT recipients at Mie University Hospital between June 2006 and September 2009. Sixteen patients were divided into the 2 groups according to enteral feeding starting postoperative day (POD) 1: 8 patients in DKT (15 g/d) administration (DKT group, for 1 week) and 8 patients in tepid water administration (non-DKT group, for 1 week). Portal venous flow, portal venous pressure, presence of fungal infection (serum level of ß-D-glucan and fungal polymerase chain reaction assay), time to first food intake, and time to first defecation were serially examined. RESULTS: Portal venous flow (mean [SD] velocity) was significantly increased in DKT group compared with non-DKT group: 47.5 (12.9) vs 31.8 (15.4) (P = .04) on POD 1, 46.8 (11.5) vs 28.8 (12.5) (P = .03) on POD 3, and 42.3 (17.2) vs 25.2 (9.0) (P = .05) on POD 5. However, mean (SD) portal venous pressures did not significantly change between the 2 groups. Between the 2 groups (DKT vs non-DKT), the day of first oral intake was not significantly different: 6.9 (2.5) vs 11.3 (8.7) (P = .061), but the mean (SD) day of first defecation was significantly shorter in the DKT group: 3.9 (1.1) vs 5.5 (2.6) (P = .02). Although fungal polymerase chain reaction assay was not significantly different between the 2 groups (4 vs 4 positive cases), the mean (SD) serum levels of ß-D-glucan were significantly lower in the DKT group than in the non-DKT group: 9.0 (7.4) vs 18.4 (15.9) pg/mL (P = .04). CONCLUSION: Early enteral feeding of DKT after LDLT increased portal vein blood flow without increasing portal vein pressure and stimulated early bowel movement, which in turn might prevent fungal translocation.

Breakthrough infection of Geotrichum capitatum during empirical caspofungin therapy after umbilical cord blood transplantation.

We experienced a breakthrough fungal infection caused by Geotrichum capitatum during empirical therapy with caspofungin. A 68-year-old male patient with refractory acute lymphoblastic leukemia had received umbilical cord blood transplantation after two courses of induction therapy. Empirical therapy with caspofungin was initiated 5 days before transplantation. Tacrolimus was continuously infused to prevent graft-versus-host disease. A minidose of methotrexate was intravenously administered on days 1 and 3 post-transplantation, which was changed to prednisolone from day 7 due to severe mucositis. During a recurrence of fever on day 11, blood cultures were found to be positive for a yeast-like organism, which was later confirmed by mass spectrometry to be G. capitatum. The serum levels of beta-D-glucan were elevated to 747 pg/mL. Caspofungin was switched to liposomal amphotericin B; however, radiological findings revealed pulmonary, splenic, and central nervous system involvement. Progressive renal and hepatic dysfunction subsequently developed. The patient died on day 25 post-transplantation secondary to the development of hemophagocytic syndrome and respiratory failure. We emphasize that recurrent febrile episodes, prolonged neutropenia, and underlying gastrointestinal mucosal damage require extreme caution due to the possibility of breakthrough infection caused by new fungal pathogens during empirical therapy with caspofungin.

Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide in a Patient with Chronic Granulomatous Disease and Active Infection: A First Report.

PURPOSE: We describe haploidentical hematopoietic cell transplantation (HCT) with high-dose post-transplant cyclophosphamide (PTCy) in a boy with x-linked chronic granulomatous disease (CGD). METHODS: A persistent and life-threatening fungal infection was the indication for HSCT. Non-myeloablative conditioning with PTCy (50 mg/kg days 3 and 4) was used in the absence of fully matched donors. RESULTS: Engraftment occurred on day 24. The patient experienced Grade 2 graft-versus-host disease of the skin and gastrointestinal tract and CMV infection, both of which were controlled. Chimerism was 100 % at days 30 and 6 months. Cessation of antifungal therapy was consistent with cure of the infection. CONCLUSIONS: Haploidentical HCT with high-dose PTCy for CGD is feasible and succeeded even in the context of active infection.

Amphotericin B versus fluconazole for controlling fungal infections in neutropenic cancer patients.

BACKGROUND: Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever. OBJECTIVES: To compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia. SEARCH METHODS: We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles. SELECTION CRITERIA: Randomised clinical trials comparing fluconazole with amphotericin B. DATA COLLECTION AND ANALYSIS: The two review authors independently assessed trial eligibility and risk of bias, and abstracted data. MAIN RESULTS: Seventeen trials (3798 patients, 381 deaths) were included. In two large three-armed trials, results for amphotericin B were combined with results for nystatin in a 'polyene' group. Because nystatin is an ineffective drug in these circumstances, this approach creates a bias in favour of fluconazole. Furthermore, most patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. There was overlap among the 'polyene' trials but we were unable to obtain any information from the trial authors or from Pfizer, the manufacturer of fluconazole, to clarify these issues. There were no significant differences in effect between fluconazole and amphotericin B, but the confidence intervals were wide. More patients dropped out of the study when they received amphotericin B, but as none of the trials were blinded decisions on premature interruption of therapy could have been biased. Furthermore, amphotericin B was not given under optimal circumstances, with premedication to reduce infusion-related toxicity, slow infusion, and with fluid, potassium and magnesium supplements to prevent nephrotoxicity. The major harms were hepatic impairment and gastrointestinal adverse effects with fluconazole and infusion-related toxicity, renal impairment and gastrointestinal adverse effects with amphotericin B. For the 2011 and 2014 updates no additional trials were identified for inclusion. AUTHORS' CONCLUSIONS: Amphotericin B has been disfavoured in several of the trials through their design or analysis, or both. Since intravenous amphotericin B is the only antifungal agent for which an effect on mortality has been shown, and since it is considerably cheaper than fluconazole, it should be the preferred agent.

The risk of deep fungal infections during biologic therapy for psoriasis.

With a growing understanding of the pathogenesis and immunological basis of psoriasis, the medical community has seen the development of more focused biological treatment options for patients suffering from the disease, which are beginning to revolutionize the treatment of psoriasis. It is already well known that certain biologics are associated with an increased risk of reactivating tuberculosis in patients with latent disease, however, with increasing use of biologic agents across indications, there has also been a rise in reports of associated deep fungal infections. The mechanism of action of these biologic anti-psoriatic therapies allows physicians to address the underlying cause of patients' symptoms. The question though, is whether this same therapeutic mechanism may predispose patients to serious infections, including deep fungal infections.

Postoperative infections after cytoreductive surgery and HIPEC for peritoneal carcinomatosis: proposal and results from a prospective protocol study of prevention, surveillance and treatment.

The incidence of infectious complications due to several contributory causes is particularly elevated and life-threatening in patients undergoing peritonectomy and HIPEC procedure for peritoneal carcinomatosis. Following a previous experience, we started a prospective protocol study of preoperative screening, perioperative prophylaxis and postoperative surveillance and treatment. A total of 111 patients with peritoneal carcinomatosis of various origin underwent CRS with HIPEC between April 2004 and December 2012. The group was divided into a pilot group of 30 patients (04/04 to 05/08) and a main group of 81 patients (06/08 to 12/12). Overall postoperative morbidity rate was 44%, with 35.8% of symptomatic infections. No post-operative mortality was observed. Microorganisms were isolated in 24 patients (80.0%) in the first group and 54 (66.7%) in the second. They were symptomatic in 18 cases (75.0%) and 25 (46.3%) cases respectively. In addition, 7 invasive candidosis were recorded (25.9%). Colon resection (P = 0.01) and duration of surgery (P = 0.0008) were associated with infection at logistic regression model. Concerning symptomatic infections, only Infection Risk Index (P = 0.009) showed significance at multivariate analysis. Despite a significant incidence of infectious complications, establishment of a prevention, surveillance and treatment protocol lead to a zero mortality rate in the observed patients of our experience. Owing to the obtained results, we suggest the use of a standardized protocol for the prevention, monitoring and treatment in all patients enrolled for cytoreductive surgery and HIPEC.

A review of the mechanism of injury and treatment approaches for illness resulting from exposure to water-damaged buildings, mold, and mycotoxins.

Physicians are increasingly being asked to diagnose and treat people made ill by exposure to water-damaged environments, mold, and mycotoxins. In addition to avoidance of further exposure to these environments and to items contaminated by these environments, a number of approaches have been used to help persons affected by exposure to restore their health. Illness results from a combination of factors present in water-damaged indoor environments including, mold spores and hyphal fragments, mycotoxins, bacteria, bacterial endotoxins, and cell wall components as well as other factors. Mechanisms of illness include inflammation, oxidative stress, toxicity, infection, allergy, and irritant effects of exposure. This paper reviews the scientific literature as it relates to commonly used treatments such as glutathione, antioxidants, antifungals, and sequestering agents such as cholestyramine, charcoal, clay and chlorella, antioxidants, probiotics, and induced sweating.

Oral infections caused by yeasts in patients with head and neck cancer undergoing radiotherapy. Identification of the yeasts and evaluation of their antifungal susceptibility.

UNLABELLED: Yeasts occur as part of the normal human microbiota. Nevertheless, some species are opportunistic, affecting immunocompromised patients such as those undergoing oncologic treatment. OBJECTIVE: To detect the presence of yeasts in patients suffering from head and neck cancer who are receiving radiation therapy and display lesions in the oral cavity, compatible with candidiasis; and to evaluate the antifungal susceptibility of the isolates recovered. METHODS: Sixty samples from patients were obtained by swabbing the oral mucosa. Identification of isolates were performed by classical taxonomic, morphological and biochemical methods as well as by using commercial identification kits. Susceptibility to antifungal drugs was determined by the agar diffusion method with Neosensitabs(®) disks. RESULTS: Forty-six samples (77%) yielded positive findings, and species recovered were: Candida albicans (22 isolates), Candida tropicalis (13 isolates), Candida parapsilosis (six strains), Candida krusei (three strains), Candida dubliniensis and Saccharomyces cerevisiae (one each). All strains were susceptible to itraconazole, clotrimazole, voriconazole, nystatin and amphotericin B. On the other hand, 65% of strains were miconazole-susceptible while 35%, showed intermediate susceptibility. With regard to ketoconazole, only three strains (7%) corresponding to C. albicans (one isolate) and C. krusei (two isolates) displayed intermediate susceptibility. Only C. krusei strains were resistant to fluconazole while all the other species were susceptible. Eventually, only six isolates (13%) were susceptible to terbinafine while the remaining strains were resistant in vitro. CONCLUSION: Early detection of etiological agents causing lesions, as well as the evaluation of their susceptibility to commonly used drugs, are crucial in order to choose the appropriate treatment that will minimize complications while improving the quality of patients' lives.

Ten-year experience with fungal peritonitis in peritoneal dialysis patients: antifungal susceptibility patterns in a North-American center.

OBJECTIVE: To describe the clinical and microbiological features associated with fungal peritonitis in peritoneal dialysis (PD) patients at Hôpital Maisonneuve-Rosemont, from August 1996 to July 2006. METHODS: Cases were retrieved from the microbiology laboratory culture registry. Antifungal susceptibility was determined by the Clinical and Laboratory Standards Institute M27A3 method. RESULTS: Among 288 PD patients (total follow-up of 7258 patient-months), nine were found with fungal peritonitis. Candida spp were identified in all of them, with a majority of non-albicans Candida species. Resistance to fluconazole, itraconazole, or voriconazole was as frequent as potential resistance to amphotericin B. No isolate was resistant to caspofungin and one was resistant to micafungin. Prior bacterial peritonitis was frequent (67%). All patients had their PD catheter removed and all of them survived. CONCLUSIONS: In our institution, fungal peritonitis in PD patients is rare. All cases were caused by Candida species. Variable susceptibility patterns were observed, which may influence the initial empirical antifungal therapy and underscore the importance of individual speciation and susceptibility testing of invasive Candida isolates.

Photodynamic inactivation of microbial pathogens: disinfection of water and prevention of water-borne diseases.

Porphyrins have been shown to act as very efficient photosensitizing agents against a broad number of microbial pathogens, including bacteria, fungi, and protozoa. This property has promising applications at a clinical level for the treatment of infectious diseases by photodynamic therapy. Moreover, this technique is also being used to address environmental problems of high significance, such as the decontamination of wastewaters, the disinfection of fish-farming tanks, the protection of animal species (e.g., amphibians and reptiles) that are endangered by pathogens whose life cycle takes place largely in aqueous media, and the control of populations of noxious insects. Such diversified applications take advantage of the availability of a truly large number of porphyrin derivatives with chemical structures that can be tailored to comply with the physical and chemical properties as well as the biological features of several milieus. In addition, the property typical of porphyrins to absorb essentially all of the wavelengths in the sun emission spectrum allows the promotion of processes largely based on natural resources with significant energy savings and low impact on ecosystems.

[Treatment and prevention of infections in cancer patients with neutropenia]. / A neutropeniás onkológiai beteg infekcióinak kezelése és megelõzése.

Prognosis of malignant diseases is significantly influenced by infectious morbidity and mortality. Thus, up to date management of cancer patients, in addition to other supportive care modalities, should also incorporate diagnostic methods and therapy of infections. In order to improve outcome, patients developing febrile neutropenia following antitumour treatment should be adequately informed regarding the risk of infections. At the same time, centres responsible for cancer patient care should set up written protocols for basic workup and empirical antibiotic therapy. Here general characteristics of neutropenic infections developing in solid tumour patients are outlined and key points for risk assessment are highlighted. In addition, options and limits of anti-infective therapy as well as prophylaxis of infections are reviewed. Importance of a fully functional institutional infection control system and multidisciplinary patient management is also emphasised.

[Cost effectiveness of posaconazole versus fluconazole/itraconazole in the prophylactic treatment of invasive fungal infections in Mexico]. / Costo efectividad de posaconazol versus fluconazol/itraconazol en el tratamiento profiláctico de las infecciones fúngicas invasivas en México.

UNLABELLED: Cost effectiveness of posaconazole versus fluconazole/itraconazole therapy in the prophylaxis against invasive fungal Infections among high-risk neutropenic patients in Mexico. OBJECTIVE: To estimate the cost effectiveness and long-term combined effects of Posaconazole versus fluconazole/itraconazole (standard azole) therapy in the prophylaxis against invasive fungal Infections among high-risk neutropenic patients in Mexico. METHODS: A previously validated Markov model was used to compare the projected lifetime costs and effects of two theoretical groups of patients, one receiving Posaconazole and the other receiving standard azole. The model estimates total costs, numbers of IFIs, and QALY per patient in each prophylaxis group. To extrapolate trial results to a lifetime horizon, the model was extended with one-month Markov cycles in which mortality risk is specific to the underlying disease. Data on the probabilities of IFI were obtained from Study Protocol PO1899. Drug costs were taken from average wholesale drug reports for 2009. Cost and health effects were discounted at 5% according to the Mexican guideline. The analysis was conducted from the Mexican healthcare perspective using 2008 unit cost prices. RESULTS: Our model projects an accumulated cost to the Mexican healthcare system per patient receiving the Posaconazol regimen of $US 5,634 compared to $US 7,463 for the standard azole regimen. The accumulated discounted effect is 3.13 LY or 2.25 QALYs per patient receiving Posaconazol, compared to 2.96 LY or 2.13 QALYs per patient receiving standard azole. Posaconazol remained the dominant strategy across each scenario. Probabilistic sensitivity analysis tested numerous assumptions about the model cost and efficacy parameters and found that the results were robust to most changes. CONCLUSION: Posaconazole provides modest incremental benefits compared with standard azole therapy in the prophylaxis against IFIs among high-risk neutropenic patients. Routine Posaconazole use appears a cost saving when the likelihood of IFIs or the cost of treatment medications is high.

In vitro antimicrobial activity of ten medicinal plants against clinical isolates of oral cancer cases.

BACKGROUND: Suppression of immune system in treated cancer patients may lead to secondary infections that obviate the need of antibiotics. In the present study, an attempt was made to understand the occurrence of secondary infections in immuno-suppressed patients along with herbal control of these infections with the following objectives to: (a) isolate the microbial species from the treated oral cancer patients along with the estimation of absolute neutrophile counts of patients (b) assess the in vitro antimicrobial activity medicinal plants against the above clinical isolates. METHODS: Blood and oral swab cultures were taken from 40 oral cancer patients undergoing treatment in the radiotherapy unit of Regional Cancer Institute, Pt. B.D.S. Health University,Rohtak, Haryana. Clinical isolates were identified by following general microbiological, staining and biochemical methods. The absolute neutrophile counts were done by following the standard methods. The medicinal plants selected for antimicrobial activity analysis were Asphodelus tenuifolius Cav., Asparagus racemosus Willd., Balanites aegyptiaca L., Cestrum diurnum L., Cordia dichotoma G. Forst, Eclipta alba L., Murraya koenigii (L.) Spreng. , Pedalium murex L., Ricinus communis L. and Trigonella foenum graecum L. The antimicrobial efficacy of medicinal plants was evaluated by modified Kirby-Bauer disc diffusion method. MIC and MFC were investigated by serial two fold microbroth dilution method. RESULTS: Prevalent bacterial pathogens isolated were Staphylococcus aureus (23.2%), Escherichia coli (15.62%), Staphylococcus epidermidis (12.5%), Pseudomonas aeruginosa (9.37%), Klebsiella pneumonia (7.81%), Proteus mirabilis (3.6%), Proteus vulgaris (4.2%) and the fungal pathogens were Candida albicans (14.6%), Aspergillus fumigatus (9.37%). Out of 40 cases, 35 (87.5%) were observed as neutropenic. Eight medicinal plants (A. tenuifolius, A. racemosus, B. aegyptiaca, E. alba, M. koenigii, P. murex R. communis and T. foenum graecum) showed significant antimicrobial activity (P < .05) against most of the isolates. The MIC and MFC values were ranged from 31 to 500 µg/ml. P. aeruginosa was observed highest susceptible bacteria (46.6%) on the basis of susceptible index. CONCLUSION: It can be concluded that treated oral cancer patients were neutropenic and prone to secondary infection of microbes. The medicinal plant can prove as effective antimicrobial agent to check the secondary infections in treated cancer patients.

Central venous catheter infections and antibiotic therapy during long-term home parenteral nutrition: an 11-year follow-up study.

BACKGROUND: Catheter-related bloodstream infections are a serious and common complication in patients receiving home parenteral nutrition (HPN). METHODS: Prevalence of infections, type of agents, and effectiveness of antibiotic therapy were evaluated in 296 patients (133 males, 163 females; mean age 58.2 +/- 13.5 years) receiving HPN for at least 3 months, from January 1995 to December 2006. Patients underwent 99,969 (331 +/- 552; minimum 91, maximum 4353) days of catheterization, corresponding to 93,236 (311 +/- 489; minimum 52, maximum 4353) days of HPN. RESULTS: Fifty-two patients (24 males and 28 females; 35 oncological and 17 nononcological) were diagnosed with 169 infections. The overall corresponding infection rate was 2.0 per 1000 days of catheterization, with a progressive, regular decrease with time. In 30 cases, immediate central venous catheter removal was necessary. Infections were eradicated in 103 of 139 (74%) cases. As to the most common causative agent, 86 (51%) infections were due to Staphylococcus epidermidis. Of these, 64 were treated from 1995 to 2004, 57 of them (89%) successfully; 22 were treated from 2005 onward, only 7 of them (32%) successfully. CONCLUSIONS: Although the global infection rate has progressively decreased over the years, S epidermidis has shown an alarming increase in resistance to antibiotic treatment in the last 2 years, suggesting the need for strategies to prevent central venous catheter infection.

Antifungal prophylaxis in adult hematopoietic stem cell transplant recipients.

Invasive fungal infections (IFIs) are a frequent, costly and potentially life-threatening complication in hematopoietic stem cell transplant (HSCT) recipients. Most prevalent among the causative pathogens are Candida spp. and Aspergillus spp. Risk factors that further increase the risk of IFIs in this patient population include allogeneic transplant and acute graft versus host disease. Among strategies to improve outcomes is the administration of antifungal prophylaxis. However, optimal administration requires the identification of patients who are at the highest risk of developing a fungal infection, thus restricting concerns of drug cost, toxicity and resistance to those most likely to benefit. Currently, there are several antifungal agents recommended by the National Comprehensive Cancer Network for the prophylaxis of IFIs. These include fluconazole, itraconazole, voriconazole, posaconazole and micafungin. Fluconazole was widely considered the standard agent for prophylaxis in patients at lower risk of mold infections. New data support the efficacy of the newer triazole posaconazole and the echinocandin micafungin in this patient population..