Department of Microbiology Bacteraemia Guideline

Enterobacteriaceae bacteraemia

• Aim
• Background
• About Enterobacteriaceae
• Antimicrobial susceptibilities
• Clinical differential diagnosis
• Antimicrobial treatment
• Supplementary Investigations
• Further actions

This document provides guidelines for doctors on the management of patients with confirmed bacteraemias (blood cultures).  This document is supplementary to, and should be used in conjunction with, the antimicrobial guidelines.

Genus: Enterobacteriaceae

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Aim

The aim of this guideline is to:

• Provide education to junior microbiology registrars
• Support communication of blood culture results from microbiologists to ward doctors
• Support ward doctors in treating and investigating bacteraemic patients

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Background

The blood culture process: (including Gram stain/Culture/MALDI/16S process):

How to use this guideline: This guideline should be used to help in the management of patients with a confirmed bacteraemia. The guideline should be used to support interaction with an infection specialist e.g. Microbiology.

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About Enterobacteriaceae

Enterobacteriaceae is the genus name for a number of species of bacteria commonly called coliforms.  They can be isolated from the blood in the context of a number of clinical infections. Coliforms rarely represent contamination.

Further information about coliforms can be found below; this should be used in conjunction with the patient’s clinical presentation to guide further management.

Clinical Information

Enterobacteriaceae
Escherichia coli: E coli is a common cause of urinary tract infections (both lower and upper). They are gastrointestinal tract commensals and typically ascend the urinary tract to cause infection. They can also cause infections in areas local to the bowel such as the biliary tree, or intra-abdominal infections, particularly if the gut wall is breached (as in perforation).  Pneumonias caused by E. coli are uncommon, but if occur, often follow aspiration and/or are hospital acquired.

E. coli can be found in clinical samples, such as urine or skin swabs, without causing disease. In this setting they are said to be colonising. E. coli can also cause diarrhoeal disease, but this is an uncommon cause of bacteraemia.

Non E. coli Enterobacteriaceae (Klebsiella, Enterobacter, Citrobacter, Morganella, Proteus, Providencia, Serratia) : These bacteria are able to colonise the human gastrointestinal tract without causing disease, but are principally considered environmental bacteria. They are less common causes of infection than E. coli, but still do cause infections, particularly in immunosuppressed, antibiotic treated or hospitalised patients. The spectrum of infections these bacteria cause can be considered the same as E. coli.

Salmonella species: Non typhi salmonella typically cause gastroenteritis, but bacteraemia is possible, especially in the immunosuppresed. S. typhi and S. paratyphi should be considered in travellers returning from an endemic area. Both typhi and non typhi salmonella bacteraemia should prompt the patient being tested for HIV.

Microbiological
The Enterobacteriaceae are a large family of Gram negative bacilli, often found in the gastrointestinal tract of humans and other animals. They are facultative anaerobes and are oxidase negative and catalase positive. Three species; Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis account for 80-95% of all Enterobacteriaceae from clinical specimens.

• Escherichia species.
  There are six species, of which four are known to cause human disease. By far the most common of these is Escherichia coli. Its ability to ferment lactose helps in its laboratory identification (however a very small percentage can be non-lactose fermenting). There are several strains of E. coli associated with human disease, some of which produce enterotoxins or other virulence factors. Some strains are encapsulated with a K antigen.
• Klebsiella spp.
  Klebsiella pneumoniae is the most frequently isolated species. They are lactose fermenting, non-motile bacilli with a very large polysaccharide capsule, which gives the colonies a distinctive mucoid appearance on the agar plate. This capsule can also be seen on the Gram stain.
• Enterobacter species are lactose fermenters. They also ferment glucose, producing acid and gas. Unlike Klebsiella species, they are usually motile and are less often capsulated. Enterobacter can readily develop resistance to beta-lactam antibiotics, due to the presence of inducible beta-lactamase enzymes such as AmpC.
• Citrobacter species take their name from their ability to grow on Simmons citrate media. They are usually non-motile non-lactose fermenters, but can sometimes be slow/late lactose fermenters. C. freundii can be mistaken for Salmonella spp. as it produced hydrogen sulphide. Their ability to agglutinate with Salmonella polyvalent antisera, can also lead to misindentification of Citrobacter spp. as Salmonella spp.
• Morganella morganii. The genus Morganella contains the single species; Morganella morganii. This organism is mobile and a non-lactose fermenter. Like Citrobacter  spp. it’s ability to agglutinate with Salmonella polyvalent antisera can lead to misidentification.
• Proteus spp. are very motile organisms, this can be seen as “swarming” on the agar plate. They can rapidly hydrolyse urea and are non-lactose fermenters. Some organisms carry an AmpC beta-lactamase enzyme which can induce resistance in the presence of beta-lactam antibiotics.
• Providencia spp. These organisms are similar to Proteus species, but do not hydrolyse urea. Another distinguishing feature from Proteus spp. is that they are motile, but do not swarm.
• Serratia spp. The most commonly isolated species are Serratia liquefaciens and Serratia marcesens. S.marcesens produces distinctive red pigmented colonies. Like Citrobacter spp., they are slow or non-lactose fermenters. Unlike Citrobacter spp., Serratia spp. are usually motile.
• Salmonella species. There are seven subspecies and over 240 serovars. They are motile, oxidase negative and non-lactose fermenters. Most produce hydrogen sulphide, with the exception of S. paratyphi A which doesn’t. Also of note, S. Typhi is a weak producer of hydrogen sulphide. Salmonellae possess lipopolysaccharide somatic (O) heat-stable antigens, and flagella (H) heat-labile antigens. S.Typhi and S. Paratyphi C produce a Vi polysaccharide capsule, which can mask the somatic antigens. Polyvalent antisera and biochemical tests are important identification methods. All isolates are submitted to the reference laboratory for serotype confirmation. S.typhi and S.paratyphi are biohazard group 3 organisms.
• Hafnia alvei is the only species in the genus Hafnia. Hafnia alvei produces grey colonies on blood agar, is motile and can resemble Salmonella spp. biochemically and can agglutinate with Salmonella polyvalent antisera

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Antimicrobial susceptibilities

Antimicrobial susceptibility results are normally available 24 hours after a positive blood culture result is available. Antibiotic choice should always be reviewed at the point.

Enterobacteriaceae causing bacteraemia may be treated with the following antibiotics IF THEY ARE SENSITIVE to that antibiotic:

• Amoxicillin
• Amoxicillin/clavulanic acid
• Cephalosporins e.g. cefuroxime
• Aztreonam
• Piperacillin-tazobactam
• Carbapenems e.g. meropenem
• Quinolones e.g. ciprofloxacin

Some commonly used antibiotics have no activity against Enterobacteriacea:

• Vancomycin
• Teicoplanin
• Linezolid
• Benzylpenicillin
• Daptomycin

Some antibiotics have activity against Enterobacteriaceae but may not be appropriate for infections associated with bacteraemia e.g. Nitrofurantoin.

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Clinical differential diagnosis

The differential diagnosis for coliform bacteraemia is broad and a full systems review is recommended to identify the source. The following should be considered:

• Intra-abdominal infection
• Peritonitis
• Hepato-biliary infection
• Urinary tract infection
• Intravascular access device infection
• Pneumonia
• Skin and soft tissue infection e.g. cellulitis/necrotising fasciitis
• Bone & joint infections
• Endocarditis and cardiac device infections
• Other: e.g. Obstetric infections, enteric fever

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Antimicrobial treatment

The table below outlines some of the common infections associated with each of the clinical syndromes. Please be aware that Enterobacteriaceae infections can present in unusual ways, and that this list is by no means exhaustive.

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Supplementary Investigations

Consider further investigations as appropriate to source of infection, please see relevant guidelines.

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Further actions

Salmonella Typhi & Salmonella Paratyphi: Notification to the local health protection unit is required.

Multidrug-resistant Gram negative bacteria: Source isolation and appropriate infection prevention and control measure are required for multidrug-resistant Gram negative bacteria (e.g. Extended-spectrum beta-lactamases and Carbapenemase producing organisms). See trust policy: Infections that require source isolation.

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