Establishing a Microbiology Program and Custom Preclarus® Bacteriology Module within PPD Laboratories’ Central Lab to Meet the Needs of Unique Customer Programs
Laboratories must constantly review their service menu to ensure they are meeting the needs of clinical trial patients and sponsors. In this blog, our microbiology section supervisor, Ronnie Heflin, provides thoughtful discussion on the challenges and considerations that surround microbiology service offerings within a central lab.
What is clinical microbiology?
Microbiology is dedicated to the identification of microorganisms, including bacteria, yeasts, fungi and viruses. Generally, bacteriology is performed using plated agar media that grows a variety of microorganisms in a controlled environment with set temperature and humidity.
Clinical microbiology testing is necessary and required by many industries, as it is the first line of defense regarding the protection of human health from biological pathogens, disease-causing bacteria, etc. For example, an organism that is normal flora in one location of the body may be pathogenic if isolated in a different one. In our central labs, we have a dedicated bacteriology team that analyzes bacteria from various sites and sources to determine if there is susceptibility or resistance to certain antibiotics.
What are some hallmarks or challenges?
Clinical microbiology, at its core, is a challenging program. Challenges include long turnaround time, lack of automation and supplies with short shelf life. In addition, cultures can be difficult to interpret and are technique dependent. Therefore, it is essential that microbiology or bacteriology programs for clinical trials are supported with a team of experienced and well-trained scientists.
Since specimens are processed (i.e. plated on various culture media) when they arrive at the central lab, incubated and reviewed the following day (or at multiple timepoints over several days), managing the workload requires staffing every day of the week. Unlike most traditional lab testing, specimens processed on a Friday cannot be read after the weekend as the bacterial overgrowth may distort the clinical picture. Our central labs are staffed over the weekend to ensure that cultures are reviewed in a timely manner.
Another challenge is obtaining and maintaining proper certifications. Subjective culture interpretation, coupled with the need for in-depth training and experience from employees, require microbiology programs to attain Clinical Laboratory Improvement Amendments (CLIA) high complexity status. This means that labs with microbiology programs have to meet the highest standards of personnel qualifications, quality control and proficiency testing in order to maintain licensure under CLIA.
On the plus side, adding new types of specimen analyses or test methods are often simple validations since they hinge primarily on a scientist’s ability to detect pathogens with defined characteristics. This means that adding a new and unique culture method is not expensive or time-consuming and does not require extensive validation periods for new equipment or reagents.
What are some special considerations for specimen collection?
Specimen collection and transport is a critical step that ensures viability and stability of microorganisms in the specimen and that ultimately provides high-quality, reliable results to customers. Bacteriology, in its simplest form, is to sample a specimen from a site on a patient and determine whether there is an organism of interest or pathogen present. If a specimen is processed/plated and read the next day with no growth, the team needs to have confidence that it is not an issue of the microorganism becoming non-viable during transport.
It is also critical that specimens from a new region or for a new study arrive within the predetermined stability window, meaning that the sample collected onto the transport media arrives in a timely manner so that the organism of interest can be recovered. One way to ensure this is to have the sample processed/plated and incubated at the clinical trial site or a nearby location. Then, the preincubated plates or isolated organisms can be sent to a central lab for further workup. This method offers two advantages, negative (no growth) cultures can be resulted on site and, since the bacterial colonies that have already grown on agar or broth media are much more resilient than organisms in a collected sample, loss of viability in transit is minimized.
Traditionally with specimen testing in other lab areas, if there is an issue with collection or transport, it becomes apparent almost immediately. For example, a non-microbiology sample incorrectly drawn in EDTA will have obvious, extremely high levels of potassium (K) that will indicate the EDTA contamination. However, for microbiology specimens, the culture will be falsely negative without an obvious clue that there was an issue at the site or during transport. Therefore, in order to maintain accurate and high-quality data for customers, specimen stability is of utmost importance.
Which services are included in a microbiology program?
In addition to culture plating and organism identification, the central lab team also utilizes a custom microbiology module, created by the same PPD team that designed our innovative Preclarus® data solutions. This module provides comprehensive workflows and reports for culture results, organism identification and antibiotic susceptibility customized for the specific type of organism being tested.
The susceptibility patterns to antibiotics are different based on the organism genera, species and/or strain, and sometimes even the location of the body it is isolated from. A certain organism may be deemed susceptible to a given antibiotic if isolated from one area of the body but may be considered resistant if taken from another area. For example, the antibiotic erythromycin may be effective on a streptococcus bacterial isolate, but ineffective in a situation where this organism is isolated from a urine culture, since this topical antibiotic cannot be used to treat a urinary tract infection.
Antibiotic susceptibility is extremely complex and requires specialized capabilities, such as source-specific, study-specific and laboratory module rules and/or interpretations. The Preclarus module reporting allows the data to easily and efficiently be analyzed, showing the efficacy of investigational therapies and antibiotics. In addition, it provides real-time, clear results to our customers and can easily be customized for unique or diverse study requirements.
In addition, we are able to provide susceptibility testing by multiple methods according to customer need, including custom minimum inhibitory concentration (MIC) panels that can determine the lowest concentration of an antimicrobial agent that inhibits the growth of a given strain of bacteria. Our central lab team also completes microbial identification by Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, providing our customers with an innovative means for rapid, cost-effective and accurate results down to the genus/species level.