Serratia Species

Microbiology

The genus Serratia, family Yersiniaceae fam.nov, order Enterobacterales ord.nov (former family Enterobacteriaceae), contains at least 15 species. Serratia marcescens is the primary pathogenic species in humans, but a few cases of human infections are caused by S. liquefaciens , S. rubidaea , S. plymuthica , S. odorifera , S. ficaria , and S . fonticola , which are diverse groups containing several biogroups based on DNA hybridization analyses. ^,

The facultatively anaerobic, motile, gram-negative bacilli are recovered readily in the laboratory on enriched, non-selective and selective enteric agar. S. marcescens was originally considered to be a nonpathogenic saprophytic water organism and often used as a biological marker to trace environmental contamination because it can produce the red pigment prodigiosin. Serratia has emerged as an important pathogen that is associated with a variety of human infections. Isolates of S. marcescens of environmental origin are more likely to be red pigmented and are of low virulence while clinical isolates are rarely pigmented. ^, Serratia spp. generally are easily identified, except for the S. liquefaciens group. Most human isolates of Serratia spp. do not ferment lactose (and therefore appear as colorless colonies on the enteric agars), but they reduce nitrate to nitrite, are catalase positive and cytochrome oxidase negative, and ferment glucose and a number of other sugars. S. marcescens and the other Serratia spp. do not produce many virulence factors. Hydrolytic enzymes, including gelatinase, lipase, and DNAse are commonly produced, an uncommon property somewhat among the members of Enterobacterales; resistance to colistin and cephalothin are also distinguishing features. These and other extracellular enzymes may be virulence factors that promote tissue invasion. The most important biochemical tests for differentiating among Serratia spp. are the finding of lysine and ornithine decarboxylase and acid production from several sugars. ^,

Epidemiology

Because Serratia spp. are not a common component of human fecal flora, human infections are thought to result from environmental contamination. Serratia can survive in harsh settings, including disinfectants, and has been mostly associated with healthcare associated infections (HAIs) in the setting of outbreaks. In neonatal intensive care units (NICUs) or pediatric intensive care units (PICUs), outbreaks have been associated with contaminated milk, parenteral nutrition or medication, liquid soap, tap water, or hospital equipment, and further dissemination has occurred through the hands of healthcare personnel. Patient risk factors include the use of intravenous or urinary catheters, ventilator treatment, long duration of hospitalization, previous antibiotic therapy, and underlying conditions such as birth weight <1500 g, prematurity, diabetes mellitus, and altered host immunity.

The Nationwide Health Safety Network presented Serratia spp. as the 11th most commonly reported pathogen from all types of pediatric healthcare-associated infection from 2015 to 2017. Serratia outbreaks have been most commonly reported in NICUs; in a review of 276 NICU outbreaks, Serratia spp. accounted for 12% of outbreaks, was the third most common pathogen, and had a mortality rate up to 7.7%. In another review of 39 NICU outbreaks between 2015 and 2017, S. marcescens was the second most common gram-negative organism which was associated with 5 of the 39 (13%) NICU outbreaks. Although bloodstream infections (BSIs) with Serratia spp. in preterm infants are not common, Serratia spp. was associated with a significantly higher risk of transmission in the NICU compared with other pathogens.

Therefore, early recognition of potential outbreaks and rapid evaluation of a common source is key in limiting the spread of Serratia infections in the healthcare setting. Genotyping of the isolates should be considered. ^, Pulse-field gel electrophoresis is the gold standard for most bacterial species; however, utilizing next-generation sequencing for targeted bacterial phylogenetic marker gene sequencing can offer higher discriminatory power. ^, Matrix-assisted laser desorption/ionization time-of-flight mass (MALDI-TOF) spectrometry is used to compare the protein spectrum of organisms to a database of reference strains in order to provide timely information in an outbreak setting. ^, Consecutive outbreaks occurring over 3–10 years in the NICU have been associated with different clones that were circulating for long periods. ^{, ,}

The most common sites for colonization are the respiratory and gastrointestinal tracts in infants and the respiratory tract in adults. Prolonged colonization can occur, particularly in immunocompromised hosts.

Clinical Manifestations

In neonates, S. marcescens typically is a HAI and broad clinical manifestations include BSI, conjunctivitis, pneumonia, UTI and meningitis. Symptoms and signs of neonatal sepsis or meningitis due to S. marcescens are indistinguishable from those caused by other pathogens, but the mortality rate can be as high as 44%. ^{, ,} Neonatal meningitis can occur in 11%–25% of infants with S. marcescens BSI, and up to 50% of cerebrospinal fluid (CSF) specimens in CNS infection can have a normal cell count and glucose level, whereas the protein concentration usually is elevated. ^, Meningitis can develop while on therapy for sepsis and can be associated with ventriculitis, hydrocephalus, or destruction of the brain parenchyma and may progress to intracranial abscess or cyst formation, similar to that of infections caused by Enterobacter sakazakii and Citrobacter koseri . Serial neuroimaging studies should be performed during therapy. Most survivors are neurologically impaired.

In children, S. marcescens is associated with BSI, pneumonia, urinary tract infection (UTI), meningitis with or without brain abscess, bone and joint infection, ocular infection, intra-abdominal infection (including peritonitis in patients undergoing dialysis), and wound infection (including surgical site infection). ^{, , ,} Although uncommon, necrotizing fasciitis due to S. marcescens in previously healthy children has been reported. ^, In older children and adults, isolation of Serratia spp. invariably is associated with an indwelling catheter or instrumentation (e.g., tracheostomy, ventilator use, bronchoscopy), causing UTIs and nosocomial pneumonia. ^, Endocarditis is mainly diagnosed in intravenous drug users. S. marcescens and other Serratia spp. also are responsible for a large proportion of eye infections, including keratitis, corneal ulcers, conjunctivitis, and endophthalmitis. ^, The last is associated with poor outcomes and can lead to complete visual loss.

Serratia infections acquired in the community can occur in children with chronic granulomatous disease (CGD) and can be the sentinel infection that leads to the diagnosis. The estimated incidence of Serratia infections in CGD patients is up to 0.98 cases per 100 patient-years, with a recurrence rate of 18%. Lymphadenitis and skin abscesses are the most common infections (44%), followed by pulmonary infections (36%) and osteomyelitis (8%). Any child with a community-acquired infection due to a Serratia spp. , particularly infection of bone or lymph nodes, should be evaluated for CGD.