The microbiology laboratory plays two major roles in antibiotic stewardship program. The first role is to provide pathogen detection and identification from the clinical specimens. This facilitates specific antibiotic therapy, which in some cases is all that is needed to provide optimal therapy. This also allows discontinuation of unnecessary antibiotic therapy which is not too uncommon. The second rule of Clinical Microbiology laboratory is to provide antibiotics susceptibility testing which facilitates strain-specific antibiotic therapy leading to deescalation of broad-spectrum antibiotics. The role of Clinical Microbiology laboratory on antibiotic stewardship is illustrated in this slide for the diagnosis of bacteremia. Here we have a septic patient that is being empirically treated with Vancomycin to cover gram-positive organisms, and the goal is to detect and identify the pathogen, which in this case is Methicillin-sensitive Staph aureus, and deescalate therapy to a beta-lactam antibiotic. Here is how it is currently done in many laboratories. On day minus one, blood culture is obtained. On day zero, positive blood culture is detected. The same day gram-staining shows gram-positive cocci in clusters, which is suggestive of Staph. Typically a day later, by biochemical testing, it is identified as Staph aureus. On day two or three the antibiotic susceptibility assays identify it as Methicillin-sensitive Staph aureus. The critical thing for the management of this patient is to deescalate therapy from Vancomycin to a penicillinase-resistant Penicillin such as nafcilin because beta-lactams have been shown to be superior to Vancomycin in patients with invasive Methicillin-sensitive Staph aureus infection. The microbiology laboratory uses a variety of conventional and non-conventional methods to guide antimicrobial therapy. The gram stain, one of the oldest tools available, can still quickly tell us if the pathogen is more likely to be Strep, Staph or Neisseria. The microbiological culture for bacteria and fungi, which is a gold standard for microbial detection can also, in a matter of one to two days, detect non-fastidious pathogens. Unconventional automated systems can be used to perform identification and antimicrobial susceptibility testing for bacteria and yeast. In the past decade, Clinical Microbiology laboratory has been revolutionized by molecular methods which allow pathogen detection, identification and even antimicrobial susceptibility testing, all in minutes to hours. For example, antigen tests with lateral flow assay such as the Cryptococcal antigen tests and Clostridium difficile rapid membrane enzyme immunoassay allow rapid detection of these pathogens in blood and stool. Nucleic acid amplification tests such as on-demand PCR or batched PCR tests are allowing rapid and accurate detection of all kinds of pathogens. In several instances, they can also simultaneously provide genotypic antibiotic susceptibility results. We now also have a new tool called MALDI-TOF or Matrix-assisted Laser Desorption Ionization Time of Flight Mass Spectrometry for unbiased identification of bacterial and fungal pathogens growing in culture in just a few minutes. Even when culture and other tests are negative but signs of infection are present, we can use an unbiased nucleic acid amplification tests to identify the pathogen. In these cases, broad range PCR combined with amplicon sequencing is used to provide pathogen detection and identification. Going back to our example of bacteremia where conventional methods allowed deescalation of therapy on day two or three, with molecular methods, positive blood cultures can be identified in real time, and in the case of Staph and enterococcus also provide information on Methicillin and Vancomycin susceptibility. All of this is expected to provide same day deescalation of therapy. In fact, this is what we and others have found when make a PCR for detection of Methicillin-resistant Staph is provided on positive blood cultures. Just by reporting Methicillin result at the same time as identification result, we could reduce the time to Vancomycin replacement and reduce Vancomycin therapy, and shorten time to patient discharge. For resistance mechanisms that cannot be detected easily with molecular methods, we can expect in the near future to see emergence of phenotypic antibiotic susceptibility testing methods that can provide same-day results, thus making early deescalation possible for all drug-bug combinations. No matter what method the lab is using, the lab should only test and report selective antibiotics in order to improve targeted antimicrobial use. The decision on which antibiotics to test and report is based on recommendations by clinical and laboratory standards institute and consensus guidelines, local antibiotic stewardship program, drugs available on hospital formulary, and drugs and methods available for testing. Given that it takes time to perform antibiotic susceptibility testing, the Clinical Microbiology laboratory also plays a critical role in periodic development of antibiograms to guide empiric therapy until patient-specific results become available. Cumulative antibiogram should provide analysis of a large number of unique isolates and should be tailored for inpatient, outpatient, emergency department, intensive care unit and other units. Here's an example of an antibiogram for gram-negative rods for Stanford Healthcare. It shows the method used, number of isolates tested per species to present susceptibility for each antibiotic and limitation of results. In conclusion, the microbiology laboratory plays an important role in antimicrobial therapy of patients with infectious diseases. However, the practitioners play a critical role in empowering the laboratory to make a diagnosis. The practitioner must order the right tests in order for the lab to detect the pathogen. The practitioner must also collect the right specimen in order for the pathogen to be detected, or otherwise a laboratory may never detect that insulting pathogen and the antibiotics as a result, and the antibiotics susceptibility results provided may not be relevant. Thank you. This concludes this session.
