By Richard R. Watkins, MD, MS, FACP, FIDSA

Associate Professor of Internal Medicine, Northeast Ohio Medical University; Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH

Dr. Watkins reports no financial relationships relevant to this field of study.

SYNOPSIS: A genomic and epidemiologic investigation of an outbreak at the National Institutes of Health Clinical Center determined that S. koreensis was an opportunistic human pathogen that persisted in a reservoir in the hospital plumbing.

SOURCE: Johnson RC, Deming C, Conlan S, et al. Investigation of a cluster of Sphingomonas koreensis infections. N Engl J Med 2018;379:2529-2539.

Sphingomonas koreensis is a nonfermenting, Gram-negative bacillus that resides in aqueous reservoirs. It is a very rare human pathogen, with only two previously published cases. Johnson and colleagues reported the results of an epidemiologic investigation of an outbreak of S. koreensis that occurred at the National Institutes of Health (NIH) Clinical Center.

NIH opened a new inpatient hospital building in 2005. In 2016, a cluster of Sphingomonas infections was identified that occurred in 37 patients starting in 2001. Between 2006 and 2016, 12 clinical isolates of S. koreensis were identified. The median length of stay was 44 days until a positive culture occurred. Nine of the 12 patients were stem-cell transplant recipients and eight had S. koreensis bacteremia. One patient had S. koreensis grow from a urine culture with a low colony count, which was thought to represent bacteriuria and not a true urinary tract infection. Three of the 11 patients died. Of the six Sphingomonas cases identified in 2016, four were S. koreensis. Because of the association between Sphingomonas and water sources, between November 2016 and December 2017 the investigators obtained samples from faucets in the rooms where patients were residing when they acquired S. koreensis infections, the main municipal intake pipe, smaller pipes supplying the rooms with known culture-positive sinks, ice machines, and the isolated components from three disassembled culture-positive sinks, including any visible biofilm. Investigators used whole-genome DNA sequencing and shotgun megagenomic sequencing to assess the clinical and environmental isolates.

S. koreensis grew in 22 of 56 (39%) samples from faucets and nine of 17 (53%) water samples collected from faucets in the rooms of patients who had S. koreensis. Nine faucets that were positive for S. koreensis were replaced, but six became recolonized within five to 90 days.

The environmental samples were resistant to multiple antibiotics, which matched the patient isolates. Furthermore, isolates taken from sink components and water samples had > 99.7% average nucleotide identity to the S. koreensis isolated from clinical samples in 2016. This is strong evidence that the sinks or water was the most likely source of the nosocomial S. koreensis outbreak. Interestingly, the chlorine concentration in the cold water was adequate, but it was well below the recommended value in the hot water. Also, the hot water temperature ranged from 46-49°C, which is lower than the hospital standard of 51°C or greater. In December 2016, the free concentration of chlorine was increased to 1.0 mg/L in the hot water, and the water temperature was increased from 46-49°C to 60°C. No further S. koreensis infections occurred after these measures were implemented. In addition, subsequent environmental cultures from sinks immersed in 71°C water baths for 20 minutes were negative.

COMMENTARY

The transmission of waterborne pathogens, such as Legionella, Pseudomonas, and nontuberculous mycobacteria, is a well-known risk in healthcare settings and occasionally can lead to institutional outbreaks. For such an event to occur at the NIH Clinical Center is disconcerting, but not unfathomable. Previous studies have shown that waterborne bacteria colonize pipes in newly constructed facilities not yet in use in which water has stagnated. This likely is the route by which the S. koreensis disseminated throughout the hospital.

The S. koreensis isolates were resistant to multiple antibiotics, including aminoglycosides, beta-lactams, and levofloxacin. They were susceptible to trimethoprim-sulfamethoxazole and ciprofloxacin. Other Sphingomonas clinical isolates were less antibiotic resistant. The pervasiveness of Sphingomonas in clean water supplies makes it a conundrum for healthcare institutions, especially for immunocompromised patients. It is notable that nine of the 12 clinical samples with S. koreensis came from stem-cell transplant patients, underscoring the risk these patients face from waterborne bacteria. The steps taken by the staff at the NIH Clinical Center to mitigate their S. koreensis outbreak are effective against many opportunistic waterborne pathogens and should be applicable to other healthcare settings.

One limitation to the study is the lack of metagenomic data for the isolates prior to 2016 from patients and sinks. Another is that the genomic methods used are not yet widely available, thus limiting the generalizability of the methods to other settings. It is hoped that as the cost of metagenomic analysis decreases, its use as part of epidemiologic investigations will become more commonplace.

Patients go to healthcare institutions with the goal of getting better and do not expect to acquire a nosocomial infection. Clinicians and microbiologists alike must be vigilant in recognizing unusual clusters of illnesses and ideally have access to sophisticated methods, such as whole-genome sequencing, to rapidly identify and curtail nosocomial outbreaks.