USP <62> Microbiological Examination of Non-sterile Products: Tests for Specified Microorganisms (Harmonized)

Some sausages, such as salami, incorporate starter cultures of molds [17] to improve flavor and reduce bacterial spoilage during curing. Penicillium nalgiovense, for example, may appear as a powdery white coating on some varieties of dry-cured sausage.A newly built home may be damp if the water used when building it is still drying out – for example, in the plaster on the walls. Excess moisture indoors can also be caused by condensation. Anotoanetta explained: “Many people wrongly think using bleach kills mould, but it actually just whitens it without removing the spores.”

Fleming resumed his vacation and returned in September. He collected the original mould and grew it in culture plates. After four days he found that the plates developed large colonies of the mould. He repeated the experiment with the same bacteria-killing results. [21] [24] [25] He concluded that the mould was releasing a substance that was inhibiting bacterial growth. [26] On testing against different bacteria, he found that the mould could kill only certain Gram-positive bacteria. [27] Staphylococcus, streptococcus, and diphtheria bacillus ( Corynebacterium diphtheriae) were easily killed, but there was no effect on typhoid bacterium ( Salmonella typhimurium) and a bacterium once thought to cause influenza ( Haemophilus influenzae). He prepared a culture method from which he could obtain the mould juice, which he called "penicillin" on 7 March 1929, "to avoid the repetition of the rather cumbersome phrase 'mould broth filtrate'." [28] [22] In his Nobel lecture of 1945 he gave a further explanation, saying: De Baere, T., G. Claeys, D. Swinne, C. Massonet, G. Verschragen, A. Muylaert and M. Vaneechouttel, 2002 Identification of cultured isolates of clinically important yeast species using fluorescent fragment length analysis of the amplified internally transcribed rRNA spacer 2 region. BMC Microbiol. 2:21 Aside from the GMP violations, why did the FDA issue a warning letter highlighting fungal contamination of a compressed tablet and multiple lots were recalled? Glyburide tablets are prescribed to control diabetes so the drug product is targeted for a specific patient population. According to a recent review article 5, the common infections that can cause serious complications in patients with diabetes include community-acquired pneumonia, urinary tract infections, necrotising fasciitis and foot ulcers. In contrast, certain rare infectious diseases occur predominantly in patients with diabetes, including malignant otitis externa, rhinocerebral mucormycosis, emphysematous cholecystitis and emphysematous pyelonephritis. Because these conditions can have serious complications, progress rapidly and/or be life-threatening, prompt recognition and treatment is imperative. Glycemic control, screening for foot ulcers and educating patients about foot care, and vaccination against pneumococcus and influenza are critically important strategies for preventing infection in diabetes patients. It is unlikely that the fungal contaminants would expose diabetes to infections. Mould contamination of sterile product manufacturing plants Wareing, Peter. "The Fungal Infection of Agricultural Produce and the Production of Mycotoxins". European Mycotoxins Awareness Network. Archived from the original on 19 October 2013 . Retrieved 3 August 2013. Moulds produce allergens (substances that can cause an allergic reaction), irritants and, sometimes, toxic substances.

For the effect on the cultures of staphylococci that Fleming observed, the mould had to be growing before the bacteria began to grow, because penicillin is only effective on bacteria when they are reproducing. Fortuitously, the temperature in the laboratory during that August was optimum first for the growth of the mould, below 20°C, and later in the month for the bacteria, when it reached 25°C. Had Fleming not left the cultures on his laboratory bench and put them in an incubator, the phenomenon would not have occurred. [41]

A large and taxonomically diverse number of fungal species form molds. The growth of hyphae results in discoloration and a fuzzy appearance, especially on food. [3] The network of these tubular branching hyphae, called a mycelium, is considered a single organism. The hyphae are generally transparent, so the mycelium appears like very fine, fluffy white threads over the surface. Cross-walls (septa) may delimit connected compartments along the hyphae, each containing one or multiple, genetically identical nuclei. The dusty texture of many molds is caused by profuse production of asexual spores ( conidia) formed by differentiation at the ends of hyphae. The mode of formation and shape of these spores is traditionally used to classify molds. [4] Many of these spores are colored, making the fungus much more obvious to the human eye at this stage in its life-cycle. Get an urgent GP appointment if you cough up blood. Call 111 if you cannot see your GP. What happens at your appointment The effectiveness of an antimicrobial preservative system in a multiple-dose, aqueous drug product is demonstrated using the methods found in USP <51>. The difference in the antimicrobial effectiveness acceptance criteria for the log reduction of bacteria versus fungi for different dosage forms ( Table 2) is a concession to the reduced effectiveness of antimicrobial preservatives against yeast and mould. The reader will notice that the acceptance criteria are not harmonised with the Ph. Eur. requiring log reductions for fungi. The author questions the less stringent requirements for fungi in USP <51> is justified. Clinical aspects of fungal infections Efforts were made to coax the mould into producing more penicillin. Heatley tried adding various substances to the medium, including sugars, salts, malts, alcohol and even marmite, without success. [63] At the suggestion of Paul Fildes, he tried adding brewing yeast. This did not improve the yield either, but it did cut the incubation time by a third. [59] The team also discovered that if the penicillin-bearing fluid was removed and replaced by fresh fluid, a second batch of penicillin could be prepared, [59] but this practice was discontinued after eighteen months due to the dangerThe tablets were manufactured at the EuroPharm Hong Kong facility using a wet granulation that was dried in a tray dryer oven at 50°C for four hours to a water content of three per cent. The granulation was held at 20°C for five to 14 days prior to tablet compression. A typical formulation is allopurinol, 100 or 300 milligrams, corn starch, FD&C Yellow No. 6 Lake (yellow tablets only), lactose, magnesium stearate and povidone. A possible source of the Rhizopus microsporus was the corn starch used in the tablet manufacture that contained two cfu of Rhizopus/g. Although the ascospores of Rhizopus microsporus are thermotolerant and would survive four hours at 50°C, it appears unlikely that a granulation dried to three per cent water content and stored at 20°C for five to 14 days prior to tablet compression would become highly contaminated due to low water activity and the short time frame.

The Infectious Diseases Society of America recommends the antifungal agent Voriconazole treatment for Aspergillus osteomyelitis for a minimum of six to eight weeks for non-immuno-compromised patients with, as necessary, surgical debridgement and stabilisation of the spine. With these patients the death rate is 20 – 30 per cent, while it is around 100 per cent for immune-compromised patients. The contaminating fungus was subsequently redefined as Exserohilium rostratum, a fungus so rare that the Tennessee state health commissioner Dr John Dreyzehner described it as a fungus most physicians never see it in a lifetime of practicing medicine. According to the ASM Manual of Clinical Microbiology, phaeohyphomycosis of the skin, subcutaneous tissue, cornea, nasal sinuses and brain have been documented. Mould and damp are caused by excess moisture. Moisture in buildings can be caused by leaking pipes, rising damp in basements or ground floors, or rain seeping in because of damage to the roof or around window frames. The Food Standards Agency (FSA) advises against salvaging mouldy bread, as porous food can be contaminated below the surface . You can’t prevent your food going mouldy, but you can slow the process down. Mould likes warm, damp conditions with plenty to feed on. A clean, dry and well-ventilated kitchen can help keep mould at bay.

This review article will examine microbial testing conducted in the pharmaceutical industry directed towards the detection, enumeration and the identification of fungi, the clinical aspects of fungal contamination and the product recalls associated with fungal contamination. It is the belief of the author that microbiologists working in the pharmaceutical and medical device industries should give fungi more attention in their microbial contamination control programmes. Compendial microbial tests Houbraken, J.; Frisvad, J.C.; Seifert, K.A.; Overy, D.P.; Tuthill, D.M.; Valdez, J.G.; Samson, R.A. (2012-12-31). "New penicillin-producing Penicillium species and an overview of section Chrysogena". Persoonia - Molecular Phylogeny and Evolution of Fungi. 29 (1): 78–100. doi: 10.3767/003158512X660571. PMC 3589797. PMID 23606767.