Got GAS? Ease the Bloat with Real-Time Whole-Genome Sequencing

Financial support: Support for this study was received from the German Research Foundation (grant no.WO 1746/1-2 toM.W. and grant no. KA 4199/ 1-1 to T.H.). Additional funding was received from the Innovative Medicines Initiative Joint Undertaking (grant no. 115737-2 to K.K., Combatting bacterial resistance in Europe—molecules against gram-negative infections [COMBACTE-MAGNET]). The funders had no role in the preparation of this manuscript. Potential conflicts of interest: All authors report no conflicts of interest relevant to this article.


Got GAS? Ease the Bloat with Real-Time Whole-Genome Sequencing
To the Editor-Annually, more than 10,000 patients in the United States acquire an infection caused by invasive group A Streptococcus (GAS). The fatality rate of this illness is 11.7%, and many infections are transmitted person to person. 1,2 Outbreak investigations of postsurgical group A Streptococcus (GAS) infections can substantially disrupt surgical throughput if staff require furloughing, and they can be extremely labor intensive when surgeons practice at multiple facilities. 3 One benefit that has received little attention is the labor-saving potential that whole-genome sequencing (WGS) offers infection preventionists (IPs) when the turnaround time is sufficiently rapid to inform investigations and mitigation efforts. 4 Here, we highlight an outbreak involving 22 surgical staff, several of whom practice at multiple facilities that often care for the same patients within a regional care network.
On day 0, patient A underwent a procedure at community hospital X, performed by surgeon I who also practices at referral hospital Y (Table 1). On day 5, patient A developed an invasive GAS surgical wound infection while at hospital X. On day 7, patient B underwent a procedure performed by surgeon II at hospital X. On day 8, patient B developed a complication requiring escalation of care to hospital Y for follow-up surgery, again performed by surgeon II. On day 13, GAS was isolated from the surgical wound of patient B while at hospital Y. The 2 GAS isolates were sent for WGS, using methods described previously. 4,5 Simultaneously, IP staff initiated a retrospective review of all laboratory results beginning 6 months prior to the first surgery. Involved surgical staff at all facilities were contacted to have their throats and groins swabbed. Mitigation planning was begun in case staff furloughing would be required pending decolonization.
The core genome sequences of the 2 isolates differed bỹ 40,000 nucleotide changes, indicating that they were genetically unrelated. 5 The WGS results were available within a week, before all staff had been swabbed and before any culture results of those that had been swabbed were available. On other occasions, results have been available in <50 hours. 4 For this event, WGS permitted earlier termination of the investigation and faster resumption to full surgical capacity, saving time, labor, and money ( Table 1). The costs in Table 1 were calculated based on material and labor costs in this region 6 for screening all involved operating room staff (n = 22). If WGS had determined that the isolates were related, the cost would have been $80.00 more for the WGS approach compared to the conventional approach (not using WGS). When WGS revealed that the isolates were unrelated, the cost savings were substantial because surgical throughput was not slowed or disrupted, and IPs were able to devote their time and efforts to other issues. Currently, WGS has become faster, less Ebola virus is an enveloped RNA virus with a filamentous appearance and a uniform diameter of~80 nm, but Ebola virus particles vary greatly in length. In general, the median particle length of Ebola viruses ranges from 974 to 1,086 nm. 7 In contrast, bacteriophage Φ6 has a pleomorphic appearance and a uniform diameter of~80 nm, 8 which is almost 10 times shorter than the average length of an Ebola virus particle (Figure 1). In microbial fermentations, small increases in hyphal length (eg, the formation of pellets or clumps) can cause large increases in broth viscosity because filamentous bioparticles have higher adhesion forces than spherical bioparticles. 9 Thus, the adhesion capability of Φ6 on PPE may be much lower than that of Ebola virus. Thus, the bacteriophage Φ6 might not be an ideal surrogate virus.
In detailed studies, Casanova et al 5 found that no Φ6 transfer to inner gloves, hands, or face among 10 healthcare workers. Only 1 healthcare worker had Φ6 on scrubs at low levels (1.4 × 10 2 ) This contamination rate was much lower than that of nonenveloped bacteriophage MS2: 2 healthcare worker had MS2 on scrubs, 1 had it on hands, and 7 had it on inner gloves (at 10 1 -10 6 ). Despite these differences, the fault trees for MS2 and Φ6 contamination suggested similar pathways. 6 Similarly, very low levels of Φ6 contamination (much lower than those of MS2) have also been reported in previous studies. 3,4 However, for the aforementioned reason, the risk the doffing protocol for Ebola-level PPE may be underestimated when Φ6 is selected as the surrogate virus. Also, the risk that the doffing protocol for Ebola-level PPE may be overestimated when MS2 is selected as the surrogate virus must be considered.
Different from Φ6 and MS2, M13 is a filamentous bacteriophage with a~900 nm particle length, 10 which is very close to the average length of Ebola viruses (Figure 1). The M13 bacteriophage can be easily cultured and detected with the visible fluorescent marker, making it an ideal surrogate virus for the biocontainment study on the Ebola-level PPE. Presumably, a more accurate contamination rate after doffing Ebola-level PPE could be achieved using the surrogate virus M13. Nevertheless, we agree with the authors that the doffing protocols should be improved for better protections against all types of viruses, especially the filamentous Ebola viruses with high adhesion capabilities. acknowledgments Financial support: No financial support was provided relevant to this article.
Potential conflicts of interest: All authors report no conflicts of interest relevant to this article.