Enterobacterales: Non-Enteric Infections and Multidrug Resistance

Definition

The Enterobacterales are an order of gram-negative bacilli that are responsible for a broad range of infections in humans and in animals. They may be motile or nonmotile, depending on the species. They are aerobic or facultatively anaerobic in growth and have a predilection for inhabiting the gastrointestinal tract. Only extragastrointestinal manifestations of disease are discussed in this chapter. Enteric infections caused by Escherichia coli are discussed in Chapter 280 .

Epidemiology

The Enterobacterales, which are among the most common pathogens to infect humans worldwide, are responsible for community-acquired, hospital-acquired, and health care–associated infections. Examples of the last category include infections acquired in nursing homes and those associated with outpatient management of cancers or hematologic malignant disease. As several species are resident components of the flora of the gastrointestinal tract, isolates of Enterobacterales may represent examples of colonization rather than true infection when found in rectal swabs, urine, wounds, or respiratory secretions. In some regions, multidrug-resistant Enterobacterales have become endemic, thereby leading to substantial problems in the management of serious infections. Although multidrug resistance in the United States is still largely health care–associated, resistant community-associated infections are continuing to emerge.

E. coli is the most common cause of urinary tract infections, accounting for more than 80% of isolates from urine in most clinical situations ( Chapter 263 ). Klebsiella spp and Proteus mirabilis are among other common causes of urinary tract infections. Enterobacterales infections in the urinary tract can range from uncomplicated cystitis to life-threatening acute pyelonephritis and sepsis. Complicated and recurrent urinary tract infections frequently occur in patients with urinary retention, anatomic abnormalities, or a need for frequent or chronic urinary catheterization. In some patients with complicated or recurrent urinary tract infections, multidrug-resistant Enterobacterales are seen.

The spread of some strains of uropathogenic E. coli account for a disproportionate percentage of disease. For example, trimethoprim-sulfamethoxazole–resistant E. coli spread in a clonal fashion in the United States (e.g., “clonal group A” and E. coli O15:K52:H1). A widely spread E. coli clone, defined by multilocus sequence typing as sequence type 131 (ST131), is associated with resistance to ciprofloxacin and production of extended-spectrum β-lactamases. This clone, which is typically associated with community-acquired urinary tract infections, has been detected in every inhabited continent.

Given that the niche of the most common Enterobacterales is in the gastrointestinal tract, it is not surprising that these bacteria are prominent as causes of abdominal infections. E. coli is the most common cause of both spontaneous bacterial peritonitis (occurring in cirrhotic patients [ Chapter 139 ]) and bacterial peritonitis arising after visceral perforation ( Chapter 128 ). Pyogenic liver abscesses ( Chapter 137 ) and intra-abdominal abscesses may also be due to E. coli . Klebsiella pneumoniae is a leading cause of pyogenic liver abscesses ( Chapter 137 ) and may also cause intra-abdominal infections, especially in patients who develop peritonitis after surgery for intra-abdominal disease.

The Enterobacterales may also cause pneumonia, although less commonly than urinary or abdominal infections. Enterobacterales respiratory tract infections are frequently hospital- and health care–associated pneumonias ( Chapters 85 and 261 ) rather than community-acquired pneumonia. K. pneumoniae , which was prominently associated with community-acquired pneumonia ( Chapter 85 ) in people with alcohol use disorder ( Chapter 364 ), has declined in significance during the past few decades. Since the 1980s, a hypervirulent K. pneumoniae has emerged to cause serious disseminated infections, typically pyogenic liver abscess ( Chapter 137 ), osteomyelitis ( Chapter 251 ), and/or endophthalmitis ( Chapter 391 ) in immunocompetent and otherwise healthy people. Although mostly antibiotic-sensitive at this time, some cases of multidrug-resistant Klebsiella have been identified.

Hospital-acquired pneumonia due to the Enterobacterales may be ventilator-associated ( Chapters 85 and 261 ), and Enterobacterales rank as the third most common causes of ventilator-associated pneumonia after Staphylococcus aureus ( Chapter 267 ) and Pseudomonas aeruginosa ( Chapter 282 ). The Enterobacterales are not natural flora of the upper airway, but mucosal injury from ventilation and any prior infection, as well as exposure to antimicrobial agents, alters the airway microbiome to predispose patients to Enterobacterales pneumonia, including pneumonia from multidrug-resistant organisms such as Enterobacter sp. and Serratia marcescens .

Outbreaks of antibiotic-resistant K. pneumoniae infection in hospitals have been prominent for more than three decades. In the hospital setting, K. pneumoniae is usually the cause of peritonitis, pneumonia, or complicated urinary tract infection. Blood stream infection arising from another site of infection, from vascular catheters, or in association with neutropenia may also occur, but patient-to-patient transmission is otherwise rare. In the past decade or so, with carbapenems considered the last line of reliable therapy for invasive infections, K. pneumoniae carbapenemase has become a substantial clinical and infection control issue in hospitals ( Chapter 261 ).

Pathobiology

Generally, Enterobacterales colonize the gastrointestinal lumen and exist in the environment, from where they are introduced into the genitourinary tract or other site to cause infection. At least 40 different virulence genes in E. coli can lead to extraintestinal infections. Among the virulence properties of these strains is the renowned ability of E. coli to adhere to uroepithelial cells. The ST131 E. coli clone is typically highly successful at causing extraintestinal infections. It belongs to “phylogenetic group” B2, which is known for extraintestinal pathogenic infections. In an evaluation of the ST131 clone, numerous extraintestinal virulence genes were found.