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A review of fungal contamination in pharmaceutical products and phenotypic identification of contaminants by conventional methods

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Microbial contamination of pharmaceutical products is one of the major reasons for product recall and manufacturing problems. Knowledge of the distribution of survival microorganisms in pharmaceutical environments is critical in the process control of non sterile and sterile pharmaceutical products. This knowledge is somewhat limited by the ubiquitous distribution of microorganisms in manufacturing facilities particularly fungal distribution. Identification of these fungi isolates from pharmaceutical environments using standard identification procedures requires experienced skilled technologists. To develop the proper corrective action when out of specification results are obtained, accurate fungal identification is needed if the contamination source has to be determined and tracked. Corrective action may not be effective if erroneous information is used to solve a given problem. This review provides guidance about knowledge of fungal contamination in pharmaceutical products and outlines an economic approach to phenotypic identification using conventional methods.
... Over the years, several mould issues associated with pharmaceutical cleanrooms, cold rooms and controlled areas have been reported. For example, several vaccine and pharmaceutical companies in Europe have experienced an increase in mould contamination due to an increase in ambient temperatures and issues with items brought into cleanrooms (Lopolito et al. 2007;Sandle 2011;Vijayakumar et al. 2012). ...
... A review of fungal contamination of pharmaceutical products reported by various authors, together with recall data relating to more than 100 pharmaceutical products collated by the Federal Drug Administration (FDA) for the years between 2000 and 2010, shows that contamination by mould and yeast was found in 21% of samples (Jimenez 2007;Vijayakumar et al. 2012;Smith et al. 2013). More recently in the year of 2012, the most serious event ever-due to fungal contamination of sterile pharmaceuticalsoccurred. ...
... The majority of the fungal contamination product recalls are due to contamination by hyaline fungi such as Aspergillus and Fusarium (Chang et al. 2006;Jimenez 2007;Vijayakumar et al. 2012;Ahearn and Stulting 2014). When compared to the hyaline fungi, melanized fungi are very difficult to treat and they are resistant to common antifungal drugs. ...
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The aim of this study was to describe the incidence of contamination of pharmaceutical products by melanized fungi and to consider control measures in relation to bioburden and cleanrooms. This study reviews and analyses pharmaceutical product recalls and offers incidence rates of fungal detection from a typical cleanrooms. The recalls include some serious cases which resulted in the loss of life. Of different types of fungal contamination incidences some of the most damaging have been due to melanized fungi ('black mould'), such as Exserohilum rostratum. The focus of the article is with melanized fungi. The study concludes that, from the review of recent pharmaceutical product recalls, fungal contamination is either increasingly common within cleanroom environments or the accuracy of sampling and the level of reporting has risen. The prevalence of melanized fungi in pharmaceutical facilities rests on specific virulence factors particular to these types of fungi, which are outlined. The article identifies a gap in the way that such fungi are screened for using available cultural methods. The article provides some control strategies, including assessing the suitability of disinfectants and biocides, for reducing the risk of melanized fungal incidences within the pharmaceutical facility. Understanding the fungal risk to pharmaceutical products remains a poorly understood and often overlooked aspect of pharmaceutical microbiology. This article helps to identify this risk and offer some guidance to those involved with pharmaceutical products manufacture in relation to bio-contamination control strategies.
... Kontaminasi pada produk juga dapat berujung tuntutan hukum dan kerugian finansial untuk bisnis farmasi. Sehingga dapat diketahui bahwa menghindari kontaminasi adalah prioritas utama di bidang farmasi (29,30) Kesimpulan Berdasarkan hasil kajian risiko proses penyediaan produk semisolid di Industri X, dapat diketahui terdapat 2 proses dengan risiko yang tinggi pada produk yaitu proses pencampuran dan pengisian. Segala risiko yang terdapat pada proses-proses tersebut termasuk kategori ALARP (As Low As Reasonably Practicable) yang memerlukan tindakan penanganan yang cepat dan pengendalian berkelanjutan agar risiko dapat dicegah maupun diminimalisir. ...
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Keselamatan pengguna adalah fokus utama industri farmasi dalam pembuatan sebuah produk yang bermutu dan terjaga keamanannya. Selama proses penyiapan produk tersebut, tentu tidak akan terlepas dari risiko kegagalan ataupun potensi berbahaya yang tidak dapat diketahui sebelumnya. Kajian risiko sudah menjadi program mandatori secara global, dengan regulasi yang bersumber pada ICH Q9 tentang Quality Risk Management dan di Indonesia sendiri diatur di Aneks ke - XIII tentang Manajemen Risiko Mutu. Tujuan penyusunan artikel ini adalah untuk mendapatkan langkah sistematis dalam mengelola risiko-risiko yang mungkin terjadi agar dapat dicegah dan diminimalisir dengan menggunakan kajian risiko. Metode yang digunakan dalam penelitian ini adalah wawancara dan diskusi di industri terkait. Hasil dari pengkajian risiko, dapat diketahui bahwa terdapat 2 proses dengan risiko yang tinggi pada produk yaitu proses pencampuran dan pengisian. Sehingga dapat disimpulkan bahwa kedua risiko tersebut menjadi prioritas dalam penanganannya dan perlu dimonitoring secara berkelanjutan. Selain itu terdapat risiko dengan nilai probabilitas(P) x severitas(S) tertinggi yaitu risiko kontaminasi pada proses pencampuran. Dengan adanya kajian risiko,diharapkan industri farmasi mampu mendeteksi lebih awal terkait risiko yang mungkin muncul dan mampu meminimalisir segala kerugian yang mungkin terjadi. Kata kunci: risiko, kajian risiko, kontaminasi
... Согласно данным FDA, за 2000-2010 гг. было отозвано более 100 серий фармацевтических продуктов, из них в 21% образцов была обнаружена контаминация плесневыми и дрожжевыми грибами [14,15]. Плесневые грибы широко распространены в окружающей среде и представляют большую опасность контаминации фармацевтических производств. ...
... 22 Subsequently, the nationwide meningitis outbreak caused by 14 000 contaminated vials of steroids from New England Compounding Pharmacy (NEC) in 2012 resulted in 64 deaths and 751 nonfatal injuries. [23][24][25] Of note, the NEC outbreak occurred after the Franck's outbreak presented in this study. The causative organism of the meningitis cases was Exserohilum rostratum, which is also a dematiaceous mold similar to that of the Bipolaris hawaiiensis in our reported cases. ...
Article
Purpose: To report the 5-year outcome of an outbreak of Bipolaris hawaiiensis fungal endophthalmitis caused by contamination of intravitreal triamcinolone from Franck's Compounding Pharmacy in Ocala, Florida. Design: Retrospective case series. Participants: Twenty-three patients (n = 25 eyes). Methods: Data was collected from the practice of a single retina specialist in Los Angeles (K.W.S) and a retina practice in New York City. Intravitreal injections of triamcinolone obtained from a single lot were subsequently found to be contaminated with Bipolaris hawaiiensis. Main outcome measures: Visual acuity; presence of vitreous cells, anterior chamber cells, or both; and detection of fungi or fungal elements in samples obtained by vitreous needle aspiration or vitreous biopsy. Results: Fungal endophthalmitis developed in 92% (23/25) of eyes. Despite aggressive local and systemic long-term therapy, severe visual loss resulted in the majority of treated eyes and the enucleated eyes showed evidence of hyphae. Conclusions: These reported cases of Bipolaris hawaiiensis endophthalmitis provide important messages for clinicians and regulatory agencies. First, patients treated with high-dose, long-term, orally administered voriconazole appeared to achieve better outcomes in treatment of Bipolaris endophthalmitis. Second, treated eyes may still show signs of deterioration, indicating the potential survival of causative organisms or fibrosis encapsulating the ciliary body, leading to hypotony. Third, several parallels can be drawn between this outbreak and the fungal meningitis outbreak after Exserohilum rostratum contamination of methylprednisolone by the New England Compounding Center.
... There are a large number of studies proving the incidence of mycotic contamination of pharmaceutical products, and referring to the fact that contaminants vary in their form of true pathogens and opportunistic pathogens. Despite this research background, few accounts of fungal degradation of pharmaceuticals and cosmetics have been published (10,11,12). Several studies have been published describing clinical hazards due to microbiologically contaminated pharmaceuticals (13)(14)(15)(16)(17). Contamination of pharmaceuticals with fungi can change physicochemical characteristics of the medicines and may be harmful or pathogenic (18). ...
Article
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Background and purpose: Tablets and ointments are used to prevent, treat, and diagnose diseases in hospitals. Although it seems that these medications are sterile in the path of the building and packaging, their mishandling or wrong application method can cause them to be contaminated. Hence, the preservation of pharmaceutical forms from contamination before and after opening the cover in hospitals is an essential measure to be taken in health care. The objective of the present study was to investigate the challenges in fungal contaminants detection and recovery in some pharmaceuticals that were high intake for patients. Materials and methods: This study was conducted in 4 teaching hospitals on 4 types of tablets and 3 types of ointments that were high intake for patients in hospitals before and after opening and usage in Sari, Iran. Fungi were identified by using standard mycology procedures. Results: The results showed that among the samples of tablets after opening the cover in the delivery room and carrying them in container by trolley, and the samples of ointments after opening and usage, the contamination rates were 70.3% and 94.4-100%, respectively. Aspergillus species such as A. flavus and A. fumigatus were the most mold species and Rhodotorula spp. was the most yeast species isolated. However, it was documented that 16.7% of some pharmaceuticals had fungal contamination ahead of opening. Conclusion: The results showed the contamination of ointments and tablets used in hospitals after opening the cover. Although the source of contamination was not investigated in the present study, the findings revealed that most of the contaminations could be due to the storage period and mishandling in pharmacies and wrong application methods after opening. Some isolated fungi can also be harmful to patients who have a weakened immune system.
... For further species identification, fungal colonies were subcultured to a second SDA plate and then incubated for 5-7 days. Fungal identification performed based on macroscopic and microscopic morphology following the keys and description given by Samson et al., Lalitha et al., and Vijayakumar et al., [13][14][15]. To compare the fungal counts with a non-sandstorm episode (to act as a control), the same procedure was followed and samples collected for one period under non-sandstorm conditions. ...
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The impact of sandstorm dust events on local air quality and public health are becoming a greater concern in the Kingdom of Saudi Arabia. Among sandstorm dust particles, airborne fungal spores cause serious respiratory ailments to those who are exposed to the dust. Although the study of dust storm material has attracted research interest, little work has been carried out in Saudi Arabia and no major study has been conducted in the Al-Zulfi, Riyadh province region. Hence, the aim of the study was to investigate airborne fungal allergen concentrations in sandstorm dust in the Al-Zulfi city, Saudi Arabia.
... There are a large number of studies proving the incidence of mycotic contamination of pharmaceutical products, and referring to the fact that contaminants vary in their form of true pathogens and opportunistic pathogens. Despite this research background, few accounts of fungal degradation of pharmaceuticals and cosmetics have been published (10,11,12). Several studies have been published describing clinical hazards due to microbiologically contaminated pharmaceuticals (13)(14)(15)(16)(17). Contamination of pharmaceuticals with fungi can change physicochemical characteristics of the medicines and may be harmful or pathogenic (18). ...
Article
Full-text available
Background and purpose: Tablets and ointments are used to prevent, treat, and diagnose diseases in hospitals. Although it seems that these medications are sterile in the path of the building and packaging, their mishandling or wrong application method can cause them to be contaminated. Hence, the preservation of pharmaceutical forms from contamination before and after opening the cover in hospitals is an essential measure to be taken in health care. The objective of the present study was to investigate the challenges in fungal contaminants detection and recovery in some pharmaceuticals that were high intake for patients. Materials and Methods: This study was conducted in 4 teaching hospitals on 4 types of tablets and 3 types of ointments that were high intake for patients in hospitals before and after opening and usage in Sari, Iran. Fungi were identified by using standard mycology procedures. Results: The results showed that among the samples of tablets after opening the cover in the delivery room and carrying them in container by trolley, and the samples of ointments after opening and usage, the contamination rates were 70.3% and 94.4-100%, respectively. Aspergillus species such as A. flavus and A. fumigatus were the most mold species and Rhodotorula spp. was the most yeast species isolated. However, it was documented that 16.7% of certain pharmaceuticals had fungal contamination ahead of opening. Conclusion: The results showed the contamination of ointments and tablets used in hospitals after opening the cover. Although the source of contamination was not investigated in the present study, the findings revealed that most of the contaminations could be due to the storage period and mishandling in pharmacies and wrong application methods after opening. Some isolated fungi can also be harmful to patients who have a weakened immune system.
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Fungi are microorganisms that can represent a high risk during the production of drugs in pharmaceutical industries. The correct identification of this contaminant has a great importance to assist in risk analysis and in taking preventive and corrective actions during the production chain. The aim of this study was to accomplish an integrative literature review regarding the occurrence of filamentous fungi in pharmaceutical industries and the methodologies used for their identification. The most common genera identified were: Aspergillus, Cladosporium, Penicillium and Fusarium, being reported in studies from three countries. The identification methodologies found were: morphological methods (evaluation of macroscopic and microscopic aspects), phenotypic characterization, proteomic analysis by MALDI-TOF MS and analysis of DNA sequences from the ITS and D1/D2 regions of the ribosomal DNA. Few studies related to the identification of filamentous fungi and their diversity in pharmaceutical industries were identified in the consulted literature, indicating that this topic needs to be further explored
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Background In silico bacterial, viral, and human truth datasets were generated to evaluate available metagenomics algorithms. Sequenced datasets include background organisms, creating ambiguity in the true source organism for each read. Bacterial and viral datasets were created with even and staggered coverage to evaluate organism identification, read mapping, and gene identification capabilities of available algorithms. These truth datasets are provided as a resource for the development and refinement of metagenomic algorithms. Algorithm performance on these truth datasets can inform decision makers on strengths and weaknesses of available algorithms and how the results may be best leveraged for bacterial and viral organism identification and characterization. Source organisms were selected to mirror communities described in the Human Microbiome Project as well as the emerging pathogens listed by the National Institute of Allergy and Infectious Diseases. The six in silico datasets were used to evaluate the performance of six leading metagenomics algorithms: MetaScope, Kraken, LMAT, MetaPhlAn, MetaCV, and MetaPhyler. Results Algorithms were evaluated on runtime, true positive organisms identified to the genus and species levels, false positive organisms identified to genus and species level, read mapping, relative abundance estimation, and gene calling. No algorithm out performed the others in all categories, and the algorithm or algorithms of choice strongly depends on analysis goals. MetaPhlAn excels for bacteria and LMAT for viruses. The algorithms were ranked by overall performance using a normalized weighted sum of the above metrics, and MetaScope emerged as the overall winner, followed by Kraken and LMAT. Conclusions Simulated FASTQ datasets with well-characterized truth data about microbial community composition reveal numerous insights about the relative strengths and weaknesses of the metagenomics algorithms evaluated. The simulated datasets are available to download from the Sequence Read Archive (SRP062063).
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Aims: The aim of this study was to develop and evaluate a real-time PCR technology for microbiological control methods to examine individualized cell therapeutics, an emerging class of pharmaceutical formulations. Methods and results: Oligonucleotide primers and hybridization probe for bacterial detection targeting the 16S rRNA gene and were adapted based on Nadkarni et al.; 2002. For detection of yeast and molds, primers and probe were designed from conserved sequences of the 18S rRNA gene in this study. The real-time PCR assays were tested on genomic DNA of Escherichia coli and Candida albicans to assess efficiency and linear dynamic range. After successful establishment of robust real-time PCRs, applicability of the assays was evaluated by extracting microbial target DNA from cell-based preparations. Different commercial DNA extraction methods were compared identifying the MagNA Pure DNA Isolation Kit III as the method of choice. Sensitivity was examined for different strains and a detection limit of 10(2) -10(3) CFU mL(-1) in a sample containing ~ 10(6) mammalian cells mL(-1) was achieved. Conclusion: This study reports the successful establishment of two qualitative real-time PCR assays enabling in general the broad range detection of microbial contaminants in a cell-based sample matrix. Significance and impact of the study: Individualized cell therapeutics tend to have a short shelf-life. Due to lengthy incubation periods compendial testing according to current pharmacopoeial guidelines may not be applicable. We report a suitable alternative method upon which future microbiological quality control methods for such products could be based on. However, to implement valid rapid microbiological testing methods using real-time PCR technology further challenges needs to be addressed. This article is protected by copyright. All rights reserved.
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A study was undertaken to compare microbial recoveries from pharmaceutical grade cleanrooms using two different incubation regimes and a general-purpose agar (Tryptone Soy Agar). One temperature regime (A) incubated plates first at 30°C to 35°C, followed by 20°C to 25°C; the second temperature regime (B) began the incubation with plates at 20°C to 25°C, followed by 30°C to 35°C. The experimental outcomes demonstrated that there was no significant difference with the total microbial count when measured using a t-test (0.05 significance level; 95% confidence interval). However, with the recovery of fungi, the second incubation regime (B), which began with the lower 20°C to 25°C temperature, produced higher incidents and numbers of fungi. While this finding might provide the basis for adopting one incubation regime over another, a review of the types of cleanrooms recovering fungi suggests that fungal incidents are low, and they are more often confined to specific areas. Thus, as an alternative, incubation regimes could be varied to suit different cleanroom environments or a selective mycological agar adopted for specific areas.
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AimsTo determine the Minimum Inhibitory Concentrations (MIC) of a range of cleanroom fungi against three disinfectants common to the pharmaceutical and healthcare sectors: biguanide (Chlorhexidine) and two quaternary ammonium compounds (benzalkonium chloride and Cetrimide).Methods and resultsThe in vitro fungicidal activities of the three biocides were studied against 112 cleanroom fungal isolates by using broth microdilution technique (CLSI M38-A2 standard).Conclusions Minimum Inhibitory Concentration (MIC) for all three biocides against hyaline fungi showed results of not more than 16 μg/ml. Alternaria showed less than 32 μg/ml and other dematiaceous fungi reported that 8 to 16 μg/ml for Biguanides and QACs. This study clearly demonstrates that the most frequently isolated microorganisms from an environmental monitoring programme may be periodically subjected to broth microdilution testing with cleanroom disinfectant agents used in the disinfection programme confirm their sensitivity profile.Significance and impact of the studyNo large collection of data exists on the activity of biocides on pharmaceutical cleanroom fungal isolates. This is the first study report with large collection of cleanroom fungal isolates tested against common biocides using the broth microdilution antifungal susceptibility testing to determine the MIC value. The data presented supports a quality control procedure for cleanroom disinfection.This article is protected by copyright. All rights reserved.
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Fungal endophthalmitis is a rare but serious infection. In March 2012, several cases of probable and laboratory-confirmed fungal endophthalmitis occurring after invasive ocular procedures were reported nationwide. We identified 47 cases in 9 states: 21 patients had been exposed to the intraocular dye Brilliant Blue G (BBG) during retinal surgery, and the other 26 had received an intravitreal injection containing triamcinolone acetonide. Both drugs were produced by Franck’s Compounding Lab (Ocala, FL, USA). Fusarium incarnatum-equiseti species complex mold was identified in specimens from BBG-exposed case-patients and an unopened BBG vial. Bipolaris hawaiiensis mold was identified in specimens from triamcinolone-exposed case-patients. Exposure to either product was the only factor associated with case status. Of 40 case-patients for whom data were available, 39 (98%) lost vision. These concurrent outbreaks, associated with 1 compounding pharmacy, resulted in a product recall. Ensuring safety and integrity of compounded medications is critical for preventing further outbreaks associated with compounded products. Download MP3 Length: 1:42
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Fungal infections are becoming increasingly frequent, with Aspergillus and Candida infections occurring most often. This article reviews the different patient groups that are susceptible to fungal infections and the techniques for identifying the causative agents. Also considered are the changing trends in the incidence of fungal infections and the spectrum of fungal species. All patients with a compromised immune system are at risk of developing fungal infections. Hospitilization itself increases the risk of fungal infections in immunocompromised patients, for example through measures such as prolonged catheterization. Neutropenia due to underlying hematological malignancy or induced by chemotherapy is an important risk factor for the development of fungal infections. The most frequent causative agents are Candida albicans and Aspergillus fumigatus. Fungal infections in this patient group are a major cause of morbidity and mortality and prevention is therefore critical. Bone marrow transplant patients are at increased risk, with invasive Aspergillus infection being the leading cause of death in this group. Solid-organ transplantation also carries an increased risk of infection because of the use of immunosuppressive therapy to limit the risk of rejection. Each type of solid-organ transplant brings its own particular risk factors. Although the majority of fungal infections in this group are caused by Candida and Aspergillus species, emerging opportunistic fungal pathogens, such as Histoplasma and Cryptococcus species are also on the increase. People infected with HIV are particularly susceptible to virulent and persistent fungal disease. Cryptococcus neoformans, Histoplasma, Penicillium marneffei and Coccidioides are the most frequently observed pathogens. In addition, superficial Candida infections may affect up to 95% of the HIV-positive population. Pneumocystis carinii, now classified as a fungus will not be considered in this review. Other high-risk groups include burns patients, those with lung disease and those undergoing surgical procedures, particularly to the gastrointestinal tract. Patients treated in intensive care units also have high rates of nosocomial infections, most frequently caused by Candida species. In addition, a number of rare congenital defects, such as chronic granulomatous disease, can lead to increased susceptibility to fungal disease. Early diagnosis of the pathogenic species is important as this can guide initial treatment. Traditionally, most information on fungal pathogens has been obtained from culture and microscopic analysis of samples taken from autopsies, but advances in molecular biology have resulted in a number of new techniques for identifying infecting species. Restriction fragment length polymorphism analysis has been used successfully to differentiate non-albicans Candida species, although the results can often be difficult to interpret. DNA hybridization analysis produces clearer banding patterns than restriction enzyme analysis, but the technique is often too time-consuming for patients in need of urgent treatment. Electrophoretic karyotyping is one of the better molecular procedures for differentiating between genetically related Candida species, but is also time-consuming and can have variable results. Two popular techniques that offer great potential for precision, sensitivity and speed of molecular typing are random amplification of polymorphic DNA and polymerase chain reaction fingerprinting. To date, however, these technologies are limited to research laboratories. Another promising technique is the use of microsatellite markers to distinguish different pathogenic strains. Although expensive and time-consuming, the technique is reliable and enables results to be obtained with small or degraded amounts of DNA. Although Candida and Aspergillus continue to be the cause of most systemic fungal infections, surveillance of fungal pathogens has identified some changing epidemiological trends. Monitoring on a national scale has revealed a steadily increasing prevalence of fungal infections over the past few decades in addition to a change in the type of infections seen. For example, a substantial shift in the epidemiology of Candida species has taken place recently, leading to an increase in non-albicans species. These species cause infections with higher complication and death rates than those resulting from C. albicans. Most worrying is the emergence of C. krusei, which is resistant to many antifungal agents. Although still rare, endemic diseases such as histoplasmosis and blastomycosis are also increasing in areas not normally associated with these diseases. This has resulted partly from more frequent global dispersal of fungi caused by increased travel and other risk factors. In addition, because of the increase in immunocompromised individuals resulting from the emergence of HIV and the use of chemotherapy and other medical interventions, new opportunistic fungi are now causing significant problems. In conclusion, many factors can increase the risk of developing fungal infection, and minimizing these risks, wherever possible, will reduce the burden of disease. New drugs or new formulations of old drugs could improve the prognosis of patients at highest risk of developing fungal infections.
Book
The first and second editions of Fungi and Food Spoilage established a reputation as the foremost book on foodborne fungi. This completely revised and updated third edition is an invaluable reference for food microbiologists investigating fungal spoilage and sources of mycotoxin contamination in foods. The introductory chapters of the book deal with the ecology of food spoilage and give an overview of how food processing, packaging and storage affect fungal growth. Subsequent chapters cover the fundamentals of classifying and naming fungi and current methods for isolation and enumeration, including general and special purpose media, incubation conditions, etc. The major part of the book provides keys, descriptions and illustrations of all yeasts and moulds commonly encountered in foods. Characteristics of the species, including their ecology and potential for mycotoxin production, are also included. The broad and practical nature of the coverage will appeal to microbiologists, mycologists and biotechnologists in the food industry, academic, research and public health institutions. Dr John Pitt and Dr Ailsa Hocking are both Honorary Research Fellows at CSIRO Food Science Australia, North Ryde, NSW, Australia. © Springer Science+Business Media, LLC 2009. All rights reserved.
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Fungi rarely cause disease outbreaks associated with use of microbe-contaminated drugs. These rare episodes typically involve a restricted spectrum of common environmental species with relatively low virulence, rather than classical pathogens. Review of data involving over-the-counter contact lens solutions and prescription drug-related recalls revealed six episodes during the past decade with significant adverse health and financial impact (including loss of vision and death). Contaminations involved fungi mostly identified with the genera Aspergillus, Exserohilum, Fusarium, Paecilomyces, and Rhizopus. These organisms are noted for their capacity to produce resistant morphotypes (chlamydoconidia, ascospores) under various adverse conditions, generally with temperature survival/tolerances markedly in excess of maximal growth temperatures. High constituent levels of melanin, trehalose and heat-shock proteins facilitate differential survival of morphotypes following exposures to toxic chemicals and temperatures above 80 °C. Adverse environmental factors that induce resistant morphotypes are suggested to occur more readily in situ than during in vitro testing. Rare unexplained, sporadic drug contamination episodes with select thermotolerant fungi may relate, in part, to resistant dormant stages.
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Mucormycosis is an invasive fungal infection with a high fatality rate. We investigated an outbreak of mucormycosis in a pediatric hospital to determine routes of pathogen transmission from the environment and prevent additional infections. A case was defined as a hospital-onset illness consistent with mucormycosis, confirmed by culture or histopathology. Case-patient medical records were reviewed for clinical course and exposure to items and locations within the hospital. Environmental samples were collected from air and surfaces. Fungal isolates collected from case-patients and the environment were identified using DNA sequencing. Five case-patients had hospital-associated cutaneous mucormycosis over an eleven month period; all subsequently died. Three case-patients had conditions known to be associated with susceptibility to mucormycosis, while two had cardiac conditions with persistent acidosis. The cases occurred on several different wards throughout the hospital, and hospital linens were the only exposure identified as common to the case-patients. Rhizopus species were recovered from 26 (42%) of 62 environmental samples from clean linens and associated areas, and from one (4%) of 25 samples from non-linen-related items. Case-patients were infected with Rhizopusdelemar, which was also isolated from cultures of clean linens and clean linen delivery bins from the off-site laundry facility. Hospital linens were identified as a vehicle that carried Rhizopusdelemar into contact with susceptible patients. Fungal species identification using DNA-based methods is useful for corroborating epidemiologic links in hospital outbreak investigations. Hospital linens should be laundered, packaged, shipped, and stored in a manner that minimizes exposure to environmental contaminants.
Article
Purpose To report a series of cases with fungal endophthalmitis occurring after intravitreal injection of triamcinolone derived from a single lot prepared by a compounding pharmacy. Design Retrospective, observational case series. Participants Seventeen eyes treated with triamcinolone obtained from a single lot subsequently found to be contaminated with Bipolaris hawaiiensis. Methods A retrospective chart review in a single retina practice was performed for 15 patients (n = 17 eyes) who received intravitreal injections of triamcinolone obtained from a single compounding pharmacy. Medical records and cytologic and microbiologic results were reviewed from December 2011 through January 2013. Main Outcome Measures Visual acuity; presence of vitreous cell, anterior chamber cell, or both; and fungal detection in samples obtained by vitreous needle aspiration or vitreous biopsy. Results Fungal endophthalmitis developed in 82% (14/17) of eyes after intravitreal triamcinolone obtained from the same lot. Median onset was 83 days (range, 6–322 days). Preinjection visual acuity ranged from 20/20 to counting fingers (median, 20/50). Median visual acuity at last follow-up was 20/400 (range, 20/30–no light perception). The most common signs and symptoms included decreased vision (57% [8/14]), vitreous cell (64% [9/14]), and anterior chamber cell (50% [7/14]). Fungus was detected by cytologic or culture examination in 7% (1/14) from initial vitreous tap. By comparison, vitreous samples obtained by pars plana vitrectomy (PPV) resulted in fungus-positive cytologic results in 43% (6/14) of eyes and positive culture results in 36% (5/14) of eyes. All culture-positive specimens (100% [5/5]) were identified as B. hawaiiensis. Overall, fungal infection was confirmed in 57% (8/14) of eyes by either cytologic or microbiologic analysis. Conclusions Fungal endophthalmitis resulting from B. hawaiiensis developed in a series of eyes after intravitreal injections of triamcinolone obtained from a single compounding pharmacy. Clinical presentation of infection can be delayed up to 10 months. Vitreous tap may be inadequate, and direct vitreous biopsy by PPV may be preferred to identify fungal endophthalmitis and facilitate prompt diagnosis and treatment.