How MALDI-ToF is Changing Clinical Microbiology

LASER TECHNOLOGY IDENTIFIES MICROBES AND IMPROVES ANTIBIOTIC THERAPY

EMBARGOED UNTIL: Thursday, September 12, 8:30 AM MDT

(Session 132, Paper D-968)

Stefan Zimmermann
Med. Microbiol. and Hygiene, Heidelberg, -null-, Germany

Email: stefan.zimmermann@med.uni-heidelberg.de

Phone: 49-6221-5638489

Matrix assisted Laser Desorption Ionization-Time of flight mass spectrometry (MALDI-ToF MS) is a complex technical phrase which means to use a laser technology to detect the mass spectrum of proteins of bacteria and identify them by a database comparison. In the modern microbiology lab it is an easy to use method to type bugs in a very short time with high accuracy. Within the last five years it became the dominating identification method in Europe and other parts of the world, replacing conventional methods using morphological or biochemical features. While biochemical typing methods require many hours or a full day, bugs are identified within minutes using MALDI techniques.

In dramatic cases of septicemia where the bacterial burden in the blood of the patient is very high, the causative microbe can be detected and identified in some cases within 4-6 hours in blood samples (compared to 24 or more hours with conventional techniques). Marc Bonten’s group in the Netherlands could show that the number of septic patients receiving appropriate antibiotic therapy, a key feature for survival in septicemia, improves from 64 to over 75%, if MALDI technology was used in a hospital lab. The mean identification time was reduced from 45 to 16 hours. James Musser’s team from Houston, Texas, proofed in a similar study that in blood stream infections (BSI) the hospital length of stay was reduced by 3 days (> 20% reduction) and the total hospital costs decreased by more than 40%, confirming an enormous benefit for the patient’s health.

Only two years ago we were able to expand the spectrum of analysis with MALDI-ToF MS from identification to antibiotic susceptibility testing (AST). Increasing antibiotic resistance of bacteria is one of the major global health problems and multiresistant bugs are on the rise worldwide. Whereas conventional resistance detection often takes over night, mass spectrometry can detect common resistance mechanisms, like extended spectrum ß-lactamases or carbapenemases, within 1-2 hours. This helps the clinicians to choose the right antibiotic within the first day of treatment. Rapid and appropriate antibiotic therapy has the highest odds ratio for survival in BSI shown in many studies. Up to now this promising technique was limited to ß-lactam antibiotics. At the ASM meeting in Denver a few month ago a breakthrough was reported from Sören Schubert’s group in Munich, Germany. Using an optimized approach and a new reagent mix made it possible to detect resistance mechanisms to other antibiotic classes, e.g. aminoglycosides, also within one to two hours.

An additional major thread of multiresistant bugs, especially gram-negative ones, is their capability to cause hospital outbreaks. A number of techniques are known to analyze those infections and type the bacterial strains of different involved patients. A disadvantage of many of these methods is the fact that they are time-consuming. MALDI technology offers a simpler and more rapid approach to match bacterial isolates to clonal outbreaks.

In summary, laser-based mass spectrometry is a powerful sword to fight infectious diseases and antibiotic resistance in up to date medicine.