Less Commonly Encountered Enterobacterales


Microbiology, Epidemiology, Clinical Manifestations, and Treatment

More than 99% of Enterobacterales recovered in clinical laboratories belong to a few dozen species. Three species— Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae —made up of more than 90% of isolates, and several other well-recognized species account for most of the remaining clinical isolates. Some less common genera have well described, clinically important member species, whereas others are newly described genera with species that have rarely been reported to cause human infections. Many newly described species were formerly classified as “atypical” members of recognized species or by various group designations, such as “enteric group” organisms, with a numerical designation. DNA relatedness and 16S ribosomal RNA gene sequencing studies have allowed the placement of these organisms into new genera. No single commercial identification system includes all these species in its database; thus, it may be appropriate for laboratories to report such organisms with questionable identities as “ Escherichia coli -like” or “ Enterobacter- like” and to refer the isolate to a reference laboratory for definitive identification when clinically warranted. Antibiotic susceptibility testing should produce reliable in vitro results since the organisms are within the Enterobacterales order for which standardized test methods are available. Recent studies have re-classified many of the former Enterobacteriaceae family members into novel families (Erwinaceae, Yersiniaceae, Hafniaceae, Morganellaceae and Budviciaceae) of the novel Enterobacterales order. However, taxonomic classification may continue to evolve as additional genetic relationships among the Enterobacterales are discovered. Similarly, our understanding of their true clinical significance will improve as better laboratory identification methods become available.

Buttiauxella Species

Buttiauxella encompasses at least seven species – B. agrestis , B. ferragutiae , B. gaviniae , B. brennerae , B. izardii , B. noackiae , and B. warmboldiae , which include environmental, nonhuman strains and opportunistic human pathogens. , , Identification can be performed via biochemical methods, 16S rRNA sequencing and proteomic methods such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Case reports describe wound infection and urinary tract infection (UTI) with Buttiauxella . , A new class of chromosomal inducible β-lactamases was reported in a clinical Buttiauxella isolate from a skull wound infection.

Cedecea Species

The genus Cedecea includes C. davisae, C. lapagei, C. neter i, and several unnamed species. Cedecea was first discovered at the Centers for Disease Control and Prevention (CDC), and its name is derived from the letters CDC. Strains of Cedecea spp. have biochemical reactions similar to those of Serratia , including lipase positivity and resistance to polymyxin B, but lack deoxyribonuclease and gelatinase activity.

Cedecea spp. are rare human pathogens, with most infections reported for adults with underlying conditions, including diabetes mellitus, malignancy, heart disease, and chronic renal disease. Cedecea has been isolated primarily from the bloodstream, respiratory tract, peritoneal fluid, or in association with soft tissue infections. There are at least 8 reported cases of bloodstream infection (BSI) due to Cedecea spp.: C. davisae (5), C. neteri (2), and C. lapagei (3). , Although Cedecea spp. have been isolated from the feces of hospitalized children, reported cases of pediatric infection are rare. There are two reported cases of nosocomial pneumonia and sepsis associated with C. lapagei, one in a late preterm infant and one in a term infant in the NICU. ,

Treatment of Cedecea infections can be challenging due to antibiotic resistance. Isolates resistant to extended-spectrum cephalosporins, aminoglycosides, and carbapenems have been reported, due to AmpC β-lactamases (i.e., class C or group 1) combined with porin deficiency and carbapenemase production including New Dehli Metallo-β-lacatamase (NDM). , ,

Edwardsiella Species

Organisms of the genus Edwardsiella are found in freshwater environments and cold-blooded animals, including fish, reptiles, and amphibians, but they occasionally are found in birds and mammals. E. tarda , E. hoshinae , E. ictaluri and E. piscicida are the four recognized species of this genus, but only E. tarda has been associated with human disease. Edwardsiella spp. are usually positive for both lysine and ornithine decarboxylase activity, but they yield a negative Voges–Proskauer test result and do not use citrate as a sole carbon source. Most clinical isolates of E. tarda produce hydrogen sulfide on Salmonella-Shigella agar and do not ferment lactose. Thus, further testing is required to exclude Salmonella spp. but most commercial identification systems including MALDI-TOF MS can reliably identify E. tarda. ,

E. tarda is not considered to be part of the normal human intestinal flora because it is recovered in less than 1% of stool samples in colonization studies. Human infections usually result from exposure to the organism from its natural environments.

A variety of human infections due to E. tarda are described, but none has been associated with outbreaks or epidemics of disease. Infections due to E. tarda can be divided into intestinal and extraintestinal. Multiple clinical and epidemiologic investigations suggest that E. tarda is a true enteropathogen because it is isolated from stool cultures significantly more frequently in people with diarrhea than those who are asymptomatic. , Intestinal infections due to E. tarda usually manifest as acute secretory enteritis associated with consumption of raw seafood or snake flesh or other aquatic exposure. Although the gastroenteritis typically is self-limited, intestinal infections in immunocompromised patients can be severe and fatal cases of E. tarda diarrhea have been described.

Extraintestinal infections include septicemia and meningitis; wound infections such as cellulitis, myonecrosis, and gas gangrene; near-drowning-associated pneumonia; cholecystitis; peritonitis; intra-abdominal, hepatic, tubo-ovarian abscesses, and peripartum chorioamnionitis; prosthetic valve endocarditis and mycotic aneurysm; pyogenic arthritis; and osteomyelitis. , , Wound infections are the most important E. tarda infections and usually occur after local trauma, such as abrasion, laceration, or penetrating injury. Wound infections also have been associated with aquatic injuries and often represent combined infection with Aeromonas hydrophila , although E. tarda has been isolated as the sole pathogen in many cases. Invasive infection most commonly occurs in adults with underlying conditions, including hepatobiliary disease, malignancy, and diabetes mellitus. In children, sickle-cell anemia has been linked to serious infections due to E. tarda, as it has been with Salmonella spp. , Osteomyelitis and meningitis have occurred in individuals with hemoglobinopathies and chronic granulomatous disease; chronic osteomyelitis in an elderly patient; and myonecrosis has been reported in an immunocompetent host. , ,

Although the precise pathogenesis is unknown, the gastrointestinal tract is presumably the site of E. tarda colonization, with invasion leading to BSI and subsequent focal infection. Case reports suggest that E. tarda in neonates may be acquired from the mother. ,

E. tarda is commonly resistant to colistin and polymyxin B. In serious invasive infections, combination therapy with an extended-spectrum cephalosporin and an aminoglycoside has been successful. Antibiotic therapy for gastroenteritis due to E. tarda usually is not indicated in immunocompetent hosts.

Ewingella americana

Ewingella americana is the only species in the genus Ewingella . Biochemically, this organism is similar to Pantoea agglomerans, but it does not use arabinose and is reliably detected by MALDI-TOF MS. Infrequent reports of E. americana infections include bacteremia, peritonitis, pneumonia, exacerbation of chronic obstructive pulmonary disease, conjunctivitis, and Waterhouse-Friderichsen syndrome in adults with underlying medical conditions. , In immunocompetent children, reported cases of E. americana include conjunctivitis in a 3-year-old and pneumonia with bacteremia in a 4-year-old. Additionally, E. americana caused a number of cases of pseudo-BSI due to contamination of blood culture bottles by the use of nonsterile citrated blood collection tubes in a children’s hospital. Multidrug resistance has been reported. ,

Hafnia Species

Hafnia alvei was the only named species of the genus Hafnia , although organisms currently classified as H. alvei can be separated into three distinct genospecies. A new species, Hafnia paralvei, was created for the former members of H. alvei genogroup. Both species can be isolated from clinical specimens, but H. alvei is likely more toxigenic. , Unlike E. tarda, H. alvei is commonly found in feces of humans and animals, in sewage, and in soil. Several reports suggest that H. alvei is one of the most frequently recovered members of the Enterobacterales in the human gastrointestinal tract. Organisms can be recovered on routine enteric media, such as MacConkey agar, appearing as colorless colonies similar to Salmonella or Shigella spp. H. alvei also appears similar to E. coli O157 on sorbitol–MacConkey agar because both these organisms commonly are D-sorbitol negative. H. alvei is lysine decarboxylase and ornithine decarboxylase positive and is positive in the Voges-Proskauer test.

H. alvei is an uncommon cause of human infection and its role remains unclear in many cases because it is often recovered concomitantly with more virulent organisms. It has been implicated as a cause of gastroenteritis in adults and children, but the evidence is not convincing. There is at least one reported case suggesting postinfectious reactive arthritis following enterocolitis due to H. alvei . Extraintestinal infections include BSI, meningitis, UTI, keratitis, endogenous endophthalmitis, wound infection, intra-abdominal abscess, and empyema in immunocompromised patients, although infection has been reported in immunocompetent hosts. In a case of chorioamnionitis and preterm birth, H. alvei was detected via 16S rDNA sequencing from a vaginal specimen.

Most infections in adults are healthcare related and associated with underlying medical conditions. Reports of extraintestinal infections in children aged 7 days to 13 years include bacteremia, meningitis, UTI, and hepatic abscess following liver transplantation. , , In contrast to adults, many children with H. alvei infections did not have identifiable comorbidities. H. alvei can harbor chromosomal AmpC β-lactamases and may be intrinsically resistant to colistin.

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