Thursday 28 February 2013

Clean Air and Containment Review

A message from the editor of the indispensable Clean Air and Containment Review journal, about the latest issue.

Clean Air and Containment Review has entered its fourth year!

CACR13 is now out featuring updates on the ISO 14644 series of standards and much else. For more information or to subscribe please visit CACR or contact John Neiger via LinkedIn and request the Contents and Abstracts.

CACR is a quarterly technical journal supported by subscribers and advertisers and it is my intention to keep it technical rather than commercial. Most articles are commissioned by me, but if you would like to write an article on any aspect of cleanroom or containment technology I would be very pleased to hear from you.

Whilst writing can I also tell you about a new book that is coming out very shortly. It is called Cleanroom Management in Pharmaceuticals and Healthcare, edited by Tim Sandle and Madhu Raju Saghee. I was involved in chapter 9: Fundamentals of pharmaceutical isolators. For more information or to order please contact the publisher. There is a very interesting pre-publication offer!

Best wishes


John Neiger, Editor
Clean Air and Containment Review – The journal to enhance your knowledge of cleanroom, clean air and containment technology

New MRSA strain

An international study has revealed that a new strain of the MRSA has made a leap from food animals to humans. Scientists from 20 institutions have conducted a research project focusing on the MRSA CC398 strain, known as pig MRSA or livestock-associated MRSA due to its prevalence among farm workers.

The study was led by Translational Genomics Research Institute (TGen).

Whole genome sequencing has shown that it was most likely an antibiotic-susceptible strain in humans in the past before transferring to food animals, where it became resistant to tetracycline and methicillin due to routine antibiotic use among animals to prevent staph infections.

This excessive application of antibiotics has caused the disease to rapidly evolve and spread back to humans.

The research was published in PLoS on-line and was titled “Persistence of Livestock Associated MRSA CC398 in Humans Is Dependent on Intensity of Animal Contact”.

The introduction to the paper reads:

“The presence of Livestock Associated MRSA (LA-MRSA) in humans is associated with intensity of animal contact. It is unknown whether the presence of LA-MRSA is a result of carriage or retention of MRSA-contaminated dust. We conducted a longitudinal study among 155 veal farmers in which repeated nasal and throat swabs were taken for MRSA detection. Periods with and without animal exposure were covered.”

The reference is:

Graveland H, Wagenaar JA, Bergs K, Heesterbeek H, Heederik D (2011) Persistence of Livestock Associated MRSA CC398 in Humans Is Dependent on Intensity of Animal Contact. PLoS ONE 6(2): e16830. doi:10.1371/journal.pone.0016830

For further details see: PLoS One

Posted by Tim Sandle

Rare Disease Day: 28th February 2013

This day at the end of February marks the sixth international Rare Disease Day.

On and around this day hundreds of patient organisations from more than 60 countries and regions worldwide are planning awareness-raising activities converging around the slogan “Rare Disorders Without Borders”.

Activities will take place across Europe, all the way to Russia, continuing to China and Japan, in the US and Canada, and as far as Australia and New Zealand.

For more information go to the website at: Rare Diseases

Posted by Tim Sandle

Wednesday 27 February 2013


The IEST has revised its standard for Product Cleanliness Levels – Applications, Requirements, and Determination.

This standard provides methods for specifying and determining product cleanliness levels for contamination-critical products. The emphasis is on contaminants that can impact product performance.

The requirements set forth in this standard are not required for all products but are intended for use in procurement and design contracts for those items where contamination control limits for parts, components, or fluids are necessary to ensure reliability and performance.

This standard provides mutually agreed-upon limits for defining significant surface cleanliness and liquid cleanliness with respect to particles and molecular residue. The standard has been modified to include alternative cleanliness level designations that are better suited to accommodate user-specific applications. These modifications are included in informative annexes at the end of the document.

For further details see IEST.

Posted by Tim Sandle

Microbial Biofilms: Current Research and Applications

A book of interest has been published on biofilms, the book is titled “Microbial Biofilms: Current Research and Applications”.

The book synopsis reads:

“Biofilms are the default mode-of-life for many bacterial species. The three-dimensional structure of the biofilm provides the associated microbial communities with additional protection from predation, toxic substances and physical perturbation. The variety of microniches provided by the biofilm also promotes a huge diversity of microbial life and metabolic potential. These complex and highly structured communities help to maintain the health of soils and waters. Current applications of biofilms include the degradation of toxic substances in soil and water, the commercial production of chemicals, and the generation of electricity. However, biofilm-based infections cause harm to millions of humans annually. In addition, biofilms can affect the quality and yield of crops and cause biofouling and microbially-induced corrosion.

In this book, leading scientists provide an up-to-date review of the latest scientific research on these fascinating microbial communities and predict future trends and growth areas in biofilm-related research.

Under the expert guidance of the editors Gavin Lear and Gillian Lewis, authors from around the world have contributed critical reviews on the most topical aspects of current biofilm research. Subjects covered include quorum sensing and social interactions in microbial biofilms, biofilms in disease, plant-associated biofilms, biofilms in the soil, applications in bioremediation, biofilms in wastewater treatment, corrosion and fouling, aquatic biofilms, microbial fuel cells, and catalytic biofilms. The book is essential for everyone interested in biofilms and their applications. It is also highly recommended for environmental microbiologists, soil scientists, medical microbiologists, bioremediation experts and microbiologists working in biocorrosion, biofouling, biodegradation, water microbiology, quorum sensing and many other areas.”

The details are:

Publisher: Caister Academic Press
Editor: Gavin Lear and Gillian D. Lewis Lincoln University, Christchurch, New Zealand and University of Auckland, New Zealand (respectively)
Publication date: February 2012 Available now!
ISBN: 978-1-904455-96-7
Price: GB £159 or US $319 (hardback)
Pages: x + 228

For more information see:

Posted by Tim Sandle

Tuesday 26 February 2013

Corynebacterium diphtheria and Diphtheria Discussed in New Online Video

Diphtheria is a serious disease caused by a toxin made by a type of bacteria known as Corynebacterium diphtheria. The toxin alters protein function in people with the condition. Currently there are several subspecies of the Gram positive bacteria recognized by scientists.

Respiratory diphtheria manifests as a sore throat with low-grade fever and an adherent pseudomembrane of the tonsils, pharynx, or nose. Another form of the disease is known as cutaneous diphtheria. People with this condition have infected skin lesions which typically lack a characteristic appearance.

On this subject, the IAQ Video Network and Cochrane & Associates have announced the release of another online video to help educate the public about issues that may impact their health. Their latest educational video discusses Corynebacterium diphtheria and diphtheria.

Posted by Tim Sandle

EU monitors bioeconomy

The European Commission has announced it will launch an observatory to map progress and impact of the development of the EU's bioeconomy.

The observatory, which is part of the EC's bioeconomy action plan, will gather data to follow the evolution of markets, to map EU, national and regional bioeconomy policies, research and innovation capacities, and the scale of related public and private investments. The Commission's in-house science service JRC will run the new resource.

The observatory will start its 3-year term in March 2013 with the aim of making the data it will collect publicly available through a dedicated web portal in 2014. In this way, the observatory will support the regional and national bioeconomy strategies now being developed by EU Member States. The observatory will track a number of performance measures, including economic and employment indicators, innovation indicators, and measures of productivity, social wellbeing and environmental quality.

Source: eurobiotech

Posted by Tim Sandle

Monday 25 February 2013

Diving for novel antibiotics

The EU-project PharmaSea will bring researchers to some of the deepest, coldest and hottest places on the planet in the hunt for novel antibiotics. 

Marine organisms that live more than 6,000 meters below the sea level are considered to be an interesting source of novel bioactive compounds as they survive under extreme conditions.

Scientists from the UK, Belgium, Norway, Spain, Ireland, Germany, Italy, Switzerland and Denmark will work together to collect and screen samples of mud and sediment from huge, previously untapped, oceanic trenches. The large-scale, four-year project is backed by more than €9.5 million of EU funding and brings together 24 partners from 14 countries from industry, academia and non-profit organisations.
The PharmaSea project focuses on biodiscovery research and the development and commercialisation of new bioactive compounds from marine organisms, including deep-sea sponges and bacteria, to evaluate their potential as novel drug leads or ingredients for nutrition or cosmetic applications.

Source: eurobiotech news

Posted by Tim Sandle

Sunday 24 February 2013

FDA acronyms and abbreviations

The FDA has updated their list of FDA related acronyms and abbreviations.

These can be found at: FDA

Posted by Tim Sandle

Saturday 23 February 2013

Identifying Bacteria - Introducing the Gram Stain

Microorganisms found in pharmaceutical and healthcare environments require identification in order to determine the species. This is important so that the origin of contamination can be assessed and the origin of contamination determined. This is commonly performed by using a standing technique called the Gram stain, which is based is a type of "phenotypic identification method" and it undertaken so that the microbiologist can understand the general profile for microorganisms.

The first step of most identification schemes is to describe the colony and cellular morphology of the microorganism. Colony morphology is normally described by directly observing growth on agar, where the colony will appear as a particular shape (such as raised, crenated, spherical and so on) and the colony will have a particular pigment. Some microbiologists will attempt to identify the microorganism based on such visual identification. This is not normally encouraged as considerable experience is required to do this and the variety of microflora cannot be characterised with any degree of accuracy. Furthermore, the characteristics of a microorganism are often dependent upon the type of culture medium used. Nevertheless, a description of the morphology can assist with further stages of identification.

Cellular staining provides important information relating to the composition of the microbial cell wall, as well as the shape of the organism. Of these, the most frequently used method is the Gram stain.

The Gram stain method employed includes the four-step technique: Crystal violet (primary stain); iodine (mordant); alcohol (decolorizer); and safranin (counter stain). Done correctly, Gram-positive organisms retain the crystal violet stain and appear blue; Gram negative organisms lose the crystal violet stain and contain only the counter-stain safranin and thus appear red. Common pitfalls in this method are that heat fixation may cause Gram-positive cells to stain Gram-negative and older cultures may give Gram-variable reaction; using too much decolorizer could result in a false Gram-negative result and not using enough decolorizer may yield a false Gram-positive result.

The Gram reaction is based on the differences in the cell wall composition for the two cellular 'groups'. The bacteria that retained the stain (the Gram-positive bacteria) have a higher peptidoglycan and lower lipid content than those that do not retain the stain (the Gram-negative bacteria). The effect of the solvent is to dissolve the lipid layer in the cell wall of the Gram-negative bacteria, thereby causing the crystal violet to leach out; whereas for Gram-positive bacteria the solvent dehydrates the thicker cell walls, blocking any diffusion of the violet-iodine complex, which closes the pores of the cell and retains the stain. There are now several automated Gram stain devices available on the market that can reduce the labour requirement required when performing several multiple Gram stains and, possibly, improve accuracy.

In addition to the difference based on cell wall, microscopic examination of the stains allows the cellular shape to be determined. Bacteria commonly fall into the categories of coccus (spherical), rod, vibrio (curved), spirilla (spiral) and plemomorphic (variable).

Posted by Tim Sandle

Friday 22 February 2013

Glucans and the Bacterial Endotoxin Test

The issue of beta-glucans and the relationship of these substances to the LAL test remains an important area not described in great detail in compendial or regulatory documents. β-Glucans (beta-glucans) are polysaccharides of D-glucose monomers linked by β-glycosidic bonds. Glucans are important because they can react with certain lysates and cause interference with the LAL test.

In relation to this area of pharmaceutical concern, Tim Sandle has written an introductory paper. It can be accessed here: glucans.

Posted by Tim Sandle

Thursday 21 February 2013

Cleanrooms and Air Quality – A Risk-Based Approach

Cleanrooms are highly controlled environments where the air quality is monitored to ensure the extreme standards of cleanliness required for the manufacture of pharmaceutical, electronic, and healthcare goods. These stringent standards usually require high fresh air rates, extensive filtering, temperature, and humidity control - all of which results in increased energy usage.

Protection from uncontrolled ingress of external ambient air is achieved by creating a pressure differential between the cleanroom and its surroundings. Contamination control is the primary consideration in cleanroom design; however, the relationships between contamination control and airflow are not well understood. Contaminants such as particles or microbes are primarily introduced to cleanrooms by people, although processes in cleanrooms may also introduce contamination. During periods of inactivity or when people are not present, it is possible to reduce airflow and maintain cleanliness conditions.

In relation to the risk assessment of cleanrooms, Tim Sandle has written a free-to-view online paper. Access it here: Sandle cleanrooms.

Posted by Tim Sandle

Wednesday 20 February 2013

Electron beam for sterilisation

Electron beam processing, commonly referred to as e-beam, is a sterilisation method which uses high energy electrons to sterilise an object. In terms of sterilisation technology, it is a method of irradiation and is sometimes described as electron irradiation - the act of applying radiation, or radiant energy, to some material.

As an introduction to the subject, Tim Sandle has written an article for the journal European Medical Hygiene.

The reference is:

Sandle, T. (2013). Electron beam processing: a rapidly developing sterilisation technology, European Medical Hygiene, Issue 3, pp914

For details, please see EMH or contact Tim Sandle for further details.

Posted by Tim Sandle

Tuesday 19 February 2013

Multi drug resistant tuberculosis

Follow this link to download the extensive 2012 WHO report on tuberculosis. A comprehensive and up-to-date assessment of the TB epidemic and progress in implementing and financing TB prevention, care and control at global, regional and country levels using data reported by 204 countries and territories that account for over 99% of the world’s TB cases.

Thanks to catchthemicrobe for the news.

Posted by Tim Sandle

Monday 18 February 2013

NIBSC becomes part of the MHRA

On 1 April 2013 the National Institute for Biological Standards and Control (NIBSC), currently a centre of the Health Protection Agency (HPA), will join the UK Medicines and Healthcare products Regulatory Agency (MHRA). The two organisations already work closely together and have common interests in managing risks associated with biological medicines, facilitating development of new ones safely and effectively, and maintaining UK expertise in this area.

All other divisions of the Health Protection Agency will transfer to a new body, Public Health England (PHE), on 1 April 2013.

NIBSC and its staff will continue to operate as normal from the present site at South Mimms in Hertfordshire, and NIBSC will continue to use business systems currently hosted by the HPA, though they will now be owned and operated by PHE.

For further details, see MHRA.

Posted by Tim Sandle

Dimorph and Filamentous Fungi

The primary risk to the immunocompromised patient arises from nosocomial infections (or hospital acquired infections). A risk to patients additionally can arise from administered medicines. Until the late 1990s the primary risk was generally regarded as arising from bacteria. However, since 2001 the second most common recall for pharmaceutical medicines has been due to fungal contamination. Moulds are ubiquitous in nature and, therefore they pose a risk to pharmaceutical manufacturing operations. Aspergillus spp., Penicillium spp., Trychophyton spp., and other filamentous fungi have, in some cases, caused significant microbial contamination issues in production environments and manufactured products.

With this important subject, Tim Sandle has written a freely accessible chapter for the book ‘Bacterial and Mycotic Infections in Immunocompromised Hosts: Clinical and Microbiological Aspects’ (edited by Maria Teresa Mascellino), which presents an introduction to this topic of fungal infections of the immunocompromised person. The book is published by OMICS Group eBooks.

The chapter can be viewed as a downloadable pdf document here.

Posted by Tim Sandle

Saturday 16 February 2013

GMP Review: Microbiology Laboratories

The current issue of the GMP Review contains an article titled “Good Practices for Pharmaceutical Microbiology Laboratories”. The article is a critical review of the 2011 WHO document on this important subject. The article has been written by Tim Sandle.

An extract from the article reads:

“The WHO document has a relatively narrow scope in terms of the perceived activities of a pharmaceutical microbiology laboratory and the scope is certainly inwards, in terms of the way a laboratory is run, rather than focusing outwards on the activities which laboratory staff might undertake. For example, the document is concerned with viable microbiological environmental monitoring within the laboratory but not with the activities of microbiology staff going into process areas to take airborne particle counts and to collect viable monitoring samples. This seems a little limited since the case for monitoring in an unclassified laboratory is somewhat debatable and the latter is something which occupies the time of many laboratory staff.”

The reference is:

Sandle, T. (2012) “Good Practices for Pharmaceutical Microbiology Laboratories”, GMP Review, Vol. 11, No.2, July 2012, pp12-14

To find out more about the GMP review go to the journal’s webpage here.

Posted by Tim Sandle

Friday 15 February 2013

ISO 15189:2012

ISO 15189:2012 ‘Medical laboratories — Particular requirements for quality and competence’ is a new standard intended to improve the quality and reliability of medical laboratories. The standard aims to provide advice to clinicians; and cover such areas as collection, transport, reception, and examination of samples and finishing with their reporting and interpretation.

ISO 15189:2012 is closely aligned to the requirements for testing and calibration laboratories ISO/IEC 17025 and the widely respected quality management standard ISO 9001.

Posted by Tim Sandle

Thursday 14 February 2013

Pharmaceutical Cleaning Validation

Cleaning validation is a requirement in industries such as pharmaceutical manufacturing which adhere to Good Manufacturing Practice (GMP) and Quality Systems Regulations (QSR), and is specific to the cleaning method and cleaner employed. Simply stated, validation is a documented guarantee that cleaning can be performed reliably and repeatedly to satisfy a predetermined level of cleanliness. Validation is achieved by demonstrating at least three times that the cleaning process removes residues down to acceptable levels.

Testing for acceptable residues includes:
  • Residue identification
  • Residue detection method selection
  • Sampling method selection
  • Setting residue acceptance criteria
  • Methods validation and recovery studies
  • Writing a procedure and training operators
The above is an extract from an article on cleaning validation, published by Pharmaceutical Online. 

Posted by Tim Sandle

Wednesday 13 February 2013

Antimicrobial effect of copper surfaces

The impact of copper surfaces has been found to have a ‘halo’ effect on surrounding non-copper materials, helping to reduce the presence of bacteria in healthcare environments, new research has found.

Several studies have been published during 2012 showed the efficacy of copper and copper alloys in reducing, or in some cases completely eradicating, bacteria on key touch surfaces in hospitals.

Further research carried out in the neonatal intensive care unit (ICU) at Aghia Sofia Children’s Hospital in Greece shows that, as well as contamination being 90% lower on copper surfaces, they also exert a ‘halo’ effect, with non-copper surfaces up to 50cm away also exhibiting a reduction of around 70% compared to surfaces not in such close proximity.

For further details, see Cleanroom Technology.

Posted by Tim Sandle

Tuesday 12 February 2013

ASM to hold meeting on 'citizen microbiology'

Citizen science involves people participating in both scientific thinking and data collection. One of several citizen science bodies around the world, the UK-EOF, describes the activity as:

“Volunteer collection of biodiversity and environmental data which contributes to expanding our knowledge of the natural environment, including biological monitoring and the collection or interpretation of environmental observations.”

Surprisingly, there are not many citizen science projects in microbiology even though microbes are of interest to the majority of the public, as well as being tractable for these kinds of studies.

However, now, in relation to the popularity of this growing trend, the American Society for Microbiology (ASM) is to host a session at a conference in May. 

According to the ASM:

"This is going to rock.  Citizen microbiology – highlighted at the American Society for Microbiology Annual Meeting in Denver in May.  The details on the session are below.  Sunday May 19 at the American Society for Microbiology General Meeting in Denver.  If you are interested in attending Register here.  If you work on some aspect of Citizen Microbiology please consider submitting an abstract for a talk or poster. The deadline is January
15 17.  We will highlight ALL accepted abstracts in some way both during the session and in blogs, tweets, interviews, etc.  So please consider participating."

Posted by Tim Sandle

Monday 11 February 2013

USP Microbiology Workshop

Microbiological Control of Compendial Articles: A USP Workshop on Current Status and Future Directions of Compendial Standards

March 18–19, 2013, USP Meetings Center, Rockville, MD

The workshop will present information on revisions to current USP Microbiology
chapters and potential and draft chapters in the areas of:

Bioburden control of nonsterile products, Microbiological Control and Monitoring of Aseptic Processing Environments.

Sterilization methods, Validation of alternate microbiological methods, Rapid/Modern microbiological
methods, Depyrogenation methods and Endotoxin Limits.

A roundtable on the recent contamination related issues in sterile compounding is also on the hot topics covered.

Key Objectives Include
  • Providing an overview of recent and current work of the USP General
  • Chapters Microbiology Expert Committee through new and revised
  • chapters and chapter proposals in order to solicit feedback on the
  • committee’s current and future standards-setting activities
  • Fostering conversation that focuses on better understanding the needs
  • of stakeholders
Speakers representing USP Microbiology Expert Committee, FDA, European Pharmacopeia and Japanese Pharmacopeia are scheduled to speak

For additional details visit the link USP Workshop on Compendial Microbiology

Or contact:

Radhakrishna Tirumalai

Posted by Tim Sandle

Sunday 10 February 2013

FDA: proposed guidance documents for 2013

The FDA has issued its work schedule for 2013. Listed below are the guidance documents that it intends to produce or update during 2013:
  • Quality Systems Approach to Pharmaceutical cGMP Regulation
  • Uniformity of In-Process Mixtures
  • Control of Highly Potent Compounds
  • Contract Manufacturing Arrangements for Drugs: Quality Agreements
  • Submission of Field Alert Reports and Biological Product Deviation Reports

For further details, see FDA

Posted by Tim Sandle

Saturday 9 February 2013

PMF Newsletter

A new edition of the Pharmaceutical Microbiology Forum (PMF) Newsletter has been issued:

In this issue:
  • The Current State of Rapid Microbiological Methods - Dr. Michael J. Miller
  • Variability and the LAL assay - Dr. Tim Sandle

This can be viewed at PMF

Posted by Tim Sandle

Friday 8 February 2013

Risk identification: different medicinal products in shared facilities

Risk identification in the manufacture of different medicinal products in shared facilities

The European Medicines Agency has published a draft document titled: “EMA: Guideline - setting health based limits for risk identification in the manufacture of different medicinal products in shared facilities”.  According to the guide: “When different medicinal products are produced in shared facilities, the potential for cross contamination becomes an issue for concern.”  The guide attempts to set out regulatory advice in relation to this. CHMP / CVMP has published this document for comment by 30 June 2013.

To view the draft, see EMA

Posted by Tim Sandle

E-guide to cleanrooms

Posted by Tim Sandle

Tuesday 5 February 2013

Pharmig News #51

The latest edition of Pharmig News has been issued and sent to members. Among the main features are:
  • New editions to the National Collection of Industrial and Marine Bacteria (NCIMB)
  • A report on Pharmig’s 20th anniversary conference, by Tim Sandle
  • A discussion on the role of rapid microbiological methods by Nigel Halls
  • A review of the FDA Guidance on Pyrogens and Endotoxin by Tim Sandle
  • A student’s experience of the University of Manchester Pharmaceutical Microbiology Master’s degree (by Sarah Harper)
  • Plus a roundup of regulatory issues of relevance to microbiologists
To obtain a copy of the newsletter, please contact the Pharmig office or follow this link

Posted by Tim Sandle

New Device Traps Particulates, Kills Airborne Pathogens

A new device called a soft x-ray electrostatic precipitator protected immune-compromised mice from airborne pathogenic bacteria, viruses, ultrafine particles, and allergens, according to a paper published online ahead of print in the journal Applied and Environmental Microbiology. The SXC ESP device multiple potential uses, and Washington University is working on licensing the technology.

"Small particles are difficult to remove, and our device overcomes that barrier," says Pratim Biswas of Washington University, St. Louis. "The device not only captures particles with a high level of efficiency that has never before been achieved; it also inactivates them. Even bioterror agents are blocked and completely inactivated."

The range of potential uses includes indoor protection of susceptible populations, such as people with respiratory illness or inhalation-induced allergies, and young children; protection of buildings from bio-terror attack; protection of individuals in hospital surgical theaters (for example, during open organ surgery); protection in cleanrooms for semiconductor fabrication; removal of ultrafine particles in power plants; and capture of diesel exhaust particulates.

The device could be used in homes, with a cost similar to that of high efficiency air cleaners. It could also be added into stand-alone indoor air cleaners, or incorporated into HVAC systems in homes, offices, and aircraft cabins. In the study, the device exceeded standards for high efficiency articulate air filters, which must be capable of removing particles larger than 0.3 micrometers with 99.97 percent efficiency.

The SXC ESP works by placing a charge on the particles and then using an electrical field to trap the particles. The SXC unit then also completely inactivates biological particles by irradiating them and photoionizing them—as UV light does, only more energetically.

Source: American Society for Microbiology

Posted by Tim Sandle

Monday 4 February 2013

Microorganisms in water pipework

The American Society for Microbiology have issued an interesting report titled “Microbes in Pipes: The Microbiology of the Water Distribution System”.

According to ASM: “Most microbes in distribution systems probably do not pose health threats, but when they form biofilms, they can cause physical damage such as corroding pipes and blocking valves. In addition to forming biofilms, some non-pathogenic microorganisms can break down chemicals used to minimize microbial growth and others may release nutrients into the distribution system that support downstream growth of opportunistic pathogens. The extent to which these processes occur in water distribution systems is largely unknown, because these ecosystems have not been characterized.”

To read more, go to the ASM website.

Posted by Tim Sandle

Sunday 3 February 2013

Antibiotic classification

An antibiotic is an agent that either kills or inhibits the growth of a microorganism. This useful infographic outlines some of the major categories of antibiotics available.

Antibiotic classification chart

The successful outcome of antimicrobial therapy with antibacterial compounds depends on several factors. These include host defense mechanisms, the location of infection, and the pharmacokinetic and pharmacodynamic properties of the antibacterial. A bactericidal activity of antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic activity and division of bacterial cells.

Antibacterial antibiotics
are commonly classified based on their mechanism of action, chemical structure, or spectrum of activity. Most target bacterial functions or growth processes. Those that target the bacterial cell wall (penicillins and cephalosporins) or the cell membrane (polymyxins), or interfere with essential bacterial enzymes (rifamycins, lipiarmycins, quinolones, and sulfonamides) have bactericidal activities. Those that target protein synthesis (macrolides,lincosamides and tetracyclines) are usually

bacteriostatic (with the exception of bactericidal aminoglycosides).

Classification of antibiotics on the basis of chemical structure:

  1. Carbohydrate containing Antibiotics:
  2. Pure saccharides antibiotics: examples; Streptozotocin
  3. Aminoglycosides: examples; Streptomycin
  4. N/O glycosides: eg. Chromomycin
  5. Other: eg; Lincomycin
  6. Macrocyclic lactone antibiotics: eg. Erythromycin
  7. Quinolones antibiotics; eg. Fluroquinolone
  8. N-containing heterocyclic antibiotics: eg. Beta-lactum
  9. O-containing heterocyclic antibiotics: eg. Cycloserine
  10. Alicyclic antibiotics: eg. Cycloheximide
  11. Aromatic antibiotics (Nitrobenzene): eg. Chloramphenicol
  12. Aliphatic amine antibiotics: eg. Spermidine
  13. Peptide antibiotics: eg. Polymyxin, Bacitracin, Gramicidin
Classification of antibiotics on the basis of origin:

Microbial origin:

  • Bacillus polymyxa: Polymyxin
  • Chromobacter violaceum: Bacitracin
  • Micromonospora spp: Gentamycin
  • Penicillium notatum: Penicillin
  • Cephalosporin spp: Cephalosporin
  • Streptomyces griseus: Streptomycin
  • S. venezuelue: Chloramphenicol
  • S. erythreus: Erythromycin
  • S. mediterranae: Rifampicin

Further categorization is based on their target specificity. "Narrow-spectrum" antibacterial antibiotics target specific types of bacteria, such as Gram-negative or Gram-positive bacteria, whereas broad-spectrum antibiotics affect a wide range of bacteria. Following a 40-year hiatus in discovering new classes of antibacterial compounds, four new classes of antibacterial antibiotics have been brought into clinical use: cyclic lipopeptides (such as daptomycin), glycylcyclines (such as tigecycline), oxazolidinones (such aslinezolid), and lipiarmycins (such as fidaxomicin).

Classification of antibiotics on the basis of range of activity (spectrum of activity):

1.Narrow spectrum:

Active towards relatively fewer microorganisms.
Examples: macrolides, Polymyxin

2. Moderate spectrum:

Active towards Gram Positive bacteria as well as some systemic and UTI causing Gram negative bacteria.
Examples: Aminoglycosides, Sulfonamide

3. Narrow-Broad spectrum:

Active against Gram positive and gram negative
Examples: Beta-lactum

4. Broad spectrum:

Active against Gram positive and Gram negative except Pseudomonas and Mycobacteria.
Examples: Chloramphenicol, Tetracycline

5. Anti-mycobacterial antibiotics:

Examples: Ethambutol, Rifampicin, Isoniazid, Pyrazinamide

Classification on the mode of action

Protein synthesis inhibitors

Major groups: aminoglycosides, tetracyclines, macrolides

General mechanism of action: Protein synthesis inhibiting antibiotics primarily target the bacterial ribosome (70S) which is made up of a small, 30S subunit and a large, 50S subunit. A ribosome is an essential, complex molecule made up of proteins and RNA and is responsible for synthesizing proteins. Aminoglycosides, macrolides, and other protein synthesis inhibitors target and prevent specific stages of protein synthesis at specific locations on 70S ribosomes. Bacterial death occurs because the cell cannot make proteins required for essential cellular processes.

Effects on humans – Humans, and other eukaryotic cells synthesize proteins using a 80S (not 70S) ribosome which is not targeted by these inhibitors. (other side effects are possible).

Nucleic acid synthesis inhibitors

Major groups: Antifolates, topoisomerase inhibitors (floroquinolones)

General mechanism of action: These antibiotics target different stages and pathways of nucleic acid (DNA, RNA…) synthesis. In summary, antifolates (includes sulfonamides) inhibit enzymes involved in folate/folic acid (vitamin B9) synthesis. Folate is an essential ingredient for the synthesis of pyrimidine and purines, two molecules found in nucleotides, the building blocks of DNA and other nucleic acids. Topoisomerase inhibitors prevent DNA replication by inhibiting topoisomerase activity. Toposiomerases are enzymes that relieve DNA supercoil stress during DNA replication. By inhibiting topoisomerase activity, DNA replication is greatly hindered and cell division rate is diminished.

Effects on humans – Humans acquire folate from dietary sources, they do not have a synthesis pathway for folate and are not affected by antifolates in the same way bacteria are. Topoisomerases can be found in human cells; however the molecular makeup of human topoisomerases differs from those found in bacteria. (other side effects are possible).
Cell wall synthesis inhibitors
Major groups: Beta-lactams (cephalosporins, penicillins)

General mechanism of action: As the name implies, this group of antibiotics inhibits certain stages in bacterial cell wall synthesis. A major structural component in the bacterial cell wall (more so in Gram-positive bacteria) is an essential polymer called peptidoglycan. Beta-lactam antibiotics bind to PBPs or penicillin binding proteins which are involved in the final stages of peptidoglycan synthesis. By inhibiting PBP function, peptidoglycan cannot be properly synthesized and the cell lyses.

Effects on humans – Human cells do not use nor synthesize peptidoglycan and are therefore not susceptible to beta-lactam antibiotics. (other side effects are possible).

Classification of antibiotics on the basis of effects of their activity:

1. Bactericidal:

Kills bacteria
Examples: Aminoglycosides, Penicillin, Cephalosporin.

2. Bacteriostatic:

Inhibits the growth of bacteria
Examples: Sulfonamide, tetracycline, chloramphenicol, trimethoprim, macrolides, Lincosamide.

Classification of antibiotics on the basis of Route of administration:

1. Oral antibiotics:

Acid stable antibiotics,
Examples; Penicillin V

2. Parenteral route:

Intravenous administration
Examples; Penicillin G
READ MORE: Controlling antimicrobial resistance

 Posted by Tim Sandle, for Pharmaceutical Microbiology

Saturday 2 February 2013

Controlling antimicrobial resistance

Antimicrobials are drugs used to treat an infectious organism, and include antibiotics (used to treat bacteria), antivirals (for viruses), antifungals (for fungal infections) and antiparasitics (for parasites).

Antibiotic resistance is a form of drug resistance whereby some (or, less commonly, all) sub-populations of a microorganism, usually a bacterial species, are able to survive after exposure to one or more antibiotics; pathogens resistant to multiple antibiotics are considered multidrug resistant(MDR) or, more colloquially, superbugs.

Nowadays fewer new antibiotics are being developed, meaning we have fewer options and stronger and stronger drugs in our antibiotics armory have to be used to treat common infections once they become resistant. This means we are now facing a possible future situation where we will be without effective antibiotics.

Antimicrobial resistance is a responsibility of each and every one of us, be it a patient, healthcare professional or policy maker. This is the theme of an interesting article in the journal European Hospital.

The article states:

“In the past four years, in more than a third of EU/EEA countries, there has been a significant increase in the trend towards combined resistance to both Klebsiella pneumoniae and E. Coli; on a more positive note methicillin- resistant Staphylococcus aureus (MRSA) has shown a decrease or stabilization in most European countries.”
  1. The seven most important measures for dealing with antimicrobial resistance are: 
  2. making sure antimicrobials are used appropriately in both humans and animals 
  3. preventing microbial infections and their spread 
  4. developing new effective antimicrobials or alternatives for treatment 
  5. cooperating with international partners to contain the risks of AMR 
  6. improving monitoring and surveillance in human and animal medicine 
  7. promoting research and innovation 
  8. improving communication, education and training.
To view the article, go to EH.

Posted by Tim Sandle

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