More rapid testing for Group B streptococcus detection

June 20, 2013

Group B streptococcus (GBS) has been shown to cause early-onset neonatal sepsis, and neonatal infection most often occurs when the infant comes into contact with this bacterium during delivery. Maternal colonization is therefore a common prerequisite for neonatal infection to occur, and as such, obstetricians routinely screen for vaginal-rectal colonization by GBS between 35 and 37 weeks. Clear guidelines have been proposed by the Centers for Disease Control for prophylaxis against GBS, and these guidelines have resulted in a significant reduction in the incidence of early onset neonatal sepsis.1

The current screening algorithm is centered around a 24- to 48-hour culture, which is traditionally the length of time required to culture the organism from a vaginal-rectal swab. While the physician is interested in asking the simple clinical question, “Is this patient colonized with GBS?” the lab receives a specimen, and is asked to isolate GBS from a number of vaginal co-colonizers. The laboratory scientist is forced to eliminate competing pathogens, and may do so by using selective enrichment media and antibiotics and optimizing growth conditions for GBS. In addition, plates may be overgrown by proteus, and to make matters even worse, a small percentage of GBS may present as non-beta hemolytic. Isolating GBS by this approach is analogous to searching for a used car on the Internet without having access to a search engine.

To overcome this hurdle, researchers have sought ways to eliminate much of the effort that goes into culture-based traditional assays. The use of chromogenic agar, for example, is one technique that allows for the detection of a specific bacterium of interest in a complex mixture of co-colonizers. Another approach is to use nucleic acid amplification technology (NAAT), in which primers are developed which target specific oligonucleotides unique to the organism in question. While this approach is truly rapid, it is more costly, and may be prohibitive in low-resource settings. To extend the analogy used above, when looking for GBS in a vaginal-rectal swab, using the NAAT approach might be akin to asking the CEO of Google to do your search for you.

What we need is a rapid test which allows for the detection of GBS in a short enough time to allow for patients who require antibiotic prophylaxis to receive sufficient treatment before delivery. The duration of antibiotic exposure is not insignificant: at least four hours of IV antibiotic is recommended for optimal prophylaxis. Considering that the active phase of labor for a multiparous woman is only two hours, it is easy to see that testing for GBS in an intrapartum setting will require that the test be processed in as short an amount of time as possible.

We have recently reported on the use of a 6.5-hour test for the isolation and detection of GBS. This test, while certainly too time-consuming for use in an intrapartum setting, may prove to be useful in the setting of threatened preterm labor. In this scenario, which affects more than 10% of pregnancies, the specimen would be collected and processed, and then patients treated accordingly. Indeed, we have recently shown that this test performed well in an antepartum setting of 356 patients, with sensitivity of 97.1% and a specificity of 88.2%.2 This test also has the unique ability to allow for the simultaneous determination of antibiotic susceptibility and pathogen identification, all within the 6.5-hour time frame.3 By utilizing a membrane-bound antibody specific for GBS, the bacterium is pulled out of a complex solution and then allowed to grow, either in the presence or absence of selected antibiotics. After a brief culture, the membrane is washed, and any bound bacteria are detected with an additional labeled antibody.

While this test may not be suitable for use yet on the labor and delivery unit, it is showing great promise in the ability to detect GBS. By converting to an ELISA format, we have already seen results in as little as 30 minutes. Once this assay has been optimized, we may soon have the ability to offer pregnant women an improved, more targeted method of GBS prophylaxis.

Jonathan Faro, MD, PhD, is an assistant professor of Ob/Gyn at UTHSC-Houston. His research interests include rapid diagnostic tests for use in antepartum patients. Through a collaboration with Nanologix, Inc., he has worked to develop a rapid method for the detection of Group B streptococcus.

References

  1. Verani JR, McGee L, Schrag SJ. Prevention of perinatal Group B streptococcal disease revised guidelines from CDC, 2010. MMWR. 2010;59(10):1-36.
  2. Faro JP, Bishop K, Riddle G, et al. Accuracy of an accelerated, culture-based assay for detection of Group B streptococcus. Infec Dis Ob Gyn. 2013;(2013):1-4.
  3. Faro JP, Bishop K, Riddle G, et al. Rapid test for growth and determination of antibiotic sensitivity of Group B streptococcus (GBS) in antepartum women. Poster presented at: SMFM 32nd Annual Meeting; February 2012; Dallas, TX.