Department of Microbiology Bacteraemia guideline

Gram negative cocci & coccobacilli

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.

Quick reference guide:

• Aim
• Background
• Bacteriological differential diagnosis
• Clinical differential diagnosis
• Technical issues
• Antimicrobial treatment

The finding of a Gram negative coccus or coccobacillus in a blood culture is unusual.  The differential diagnosis for gram negative coccobacilli in particular is extensive and requires a thorough systemic review of the patient.  Please contact Microbiology for further advice regarding investigations and/or treatment following the systemic review, if required.

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Gram stain: Gram negative Cocci & coccobacilli

Aim

The aim of this guideline is to:

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

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Background

The blood culture process: Timings of culture, identification, susceptibility tests and clinical liaison.
How to use this guideline: Support interaction with microbiology staff (not replace interaction with microbiology staff).

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Bacteriological differential diagnosis (Gram guideline only)

Gram negative cocci and coccobacilli are unusual findings in blood cultures and can represent a wide range of possible infections when they are seen.

Possible bacterial diagnoses:

Neiserria spp: Gram negative cocci that occur singly or more commonly in pairs.  Of most concern would be neiserria meningitidis³

Moraxella spp: Gram negative coccobacilli that grow in pairs or short chains⁴.

Pasturella spp: Gram negative cells that can be oval, spherical or rod shaped, which occur singly, in pairs or short chains⁵.

Haemophilus spp: Gram negative pleomorphic cells that can be spherical, oval or varying length rods⁶.

Kingella spp: Short gram negative rods that often grow in pairs or short chains⁶

Aggregatibacter spp: Gram negative coccobacillus or short rod, although rods often predominate.  They occur singly or in pairs and more rarely in short chains.  They often stain irregularly.  Some species produce filamentous forms⁶.

Cardiobacterium spp: Irregularly staining pleomorphic or straight rods of variable length with rounded ends, sometimes producing long filaments.  They occur singly, in pairs, short chains and rosette clusters⁶.

Eikenella spp:  Small, slender gram negative rods, that can be coccobacilli⁶.

Acinetobacter spp: Gram negative coccobacilli that may retain crystal violet (gram positive) staining and so appear Gram variable.  They can be pleomorphic and may become coccoid, appearing as diplococci⁷.

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Clinical differential diagnosis

These organisms can cause a wide range of infections from head to toe, including meningitis, infective endocarditis, pneumonia, epiglottitis (and other upper respiratory tract infections), septic arthritis, osteomyelitis and skin and soft-tissue infections.

Neiserria meningitidis is the cause of meningococcal sepsis and meningitis.

Other Neiserria spp are human commensal organisms as well as potential pathogens³.

Moraxella spp are most commonly pathogens of the upper and lower respiratory tract, although they are rarely isolated from blood cultures.  Immunocompromised patients are at risk of becoming bacteraemic in association with a pneumonia or upper respiratory tract infection with these organisms.  Rare cases of intra-vascular prosthetic infection and infective endocarditis have been reported⁴.

Pasturella spp are most commonly associated with skin and soft tissue infections and more rarely osteomyelitis or septic arthritis following exposure to dog or cat saliva (i.e. following a bite or a pet licking a pre-existing wound)⁵.

Haemophilus spp are associated with a wide range of infections, including upper and lower respiratory tract infections (including epiglottitis), skeletal infections, meningitis and puerperal sepsis.  Haemophilus influenzae is the most common of the pathogenic haemophilus species, and is by far the most likely to be isolated from blood cultures.  The HiB immunisation has reduced the incidence of many of these infections: a history of immunisation should be taken, especially in children, who are at increased risk⁶.

Haemophilus spp, especially H. parainfluenzae are common commensals of the respiratory tract.

Other Haemophilus spp are known to cause infective endocarditis and are part of the HACEK* group of organisms⁶.

Kingella spp are most commonly a pathogen of children under 5 years of age, causing bone and joint infections and bacteraemias (50% have skeletal foci and 50% have an occult source, presumed to be the respiratory tract).   Kingella kingae is the most common member of the species to cause skeletal infections with septic arthritis of large weight-bearing joints (knee, ankle) the most common. 

Endocarditis due to Kingella spp can be seen in all ages (HACEK*).   Case reports document a variety of infections including pneumonia, epiglottitis, meningitis, soft tissue infections and ocular infections⁶.

Aggregatibacter actinomycetemcomitans, aphrophilus and segnis are members of the HACEK* group of organisms that cause endocarditis, most commonly in patients with underlying valvular heart disease.  These are slow growing organisms and are rarely isolated in blood cultures and may be a cause of ‘culture negative’ endocarditis.  Aggregatibacter spp are closely related to Haemophilus spp⁶.

Cardiobacterium spp (C. hominis & C. valvarum) almost exclusively cause infective endocarditis (HACEK*), most commonly in patients with an underlying anatomic defect.  They are part of the normal flora of the nose, mouth and throat and are occasionally found on other mucus membranes and in the GI tract⁶.

Eikenella corrodens is part of the normal flora oral and upper respiratory tract flora and can be found on other mucus membranes.  It is most commonly part of a mixed infection (commonly with streptococci).  Infections can be associated with underlying head and neck malignancies.  It is also associated with human bite wounds and upper respiratory tract infections.  Skin and soft tissue infections can be severe and may be associated with underlying osteomyelitis.  It is another member of the HACEK* group, and is normally associated with an indolent infective endocarditis, although acute cases have been reported.  Endocarditis is most common in people who inject drugs or those with abnormal heart valves⁶.

Acinetobacter species
These organisms are saprophytes found in the soil and water and can colonise moist skin.  They remain viable in the environment for long periods and have been isolated from inanimate objects within the patient environment.  Acinetobacter baumanii is recognised as an opportunistic hospital acquired infection, most commonly affecting ICU or burns patients that can cause bacteraemia.  The most common sources are lines and the respiratory tract.  A. baumanii are multi-resistant and treatment choices should be reviewed in light of susceptibility testing and identification of the organism.  Other, more susceptible, Acinetobacter species are sometimes isolated from blood cultures and may often represent contamination with environmental flora at the time of taking the cultures (clinical correlation is required)^7,8.

*HACEK comprises a group of morphologically similar aerobic and facultatively anaerobic gram negative organism that are known to cause infective endocarditis.  They are normal commensal organisms of the oropharynx and upper respiratory tract.

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Technical issues

Specificity/Common bacteriological misdiagnoses:

All gram stains give a provisional idea of the identification of an organism and require growth of the organism for full identification.  These organisms represent unusual findings on gram stains of blood culture samples.  Many exist in more than one form and/or stain irregularly and therefore may be mis-identified as each other.  Culture growth allows for further biochemical and molecular testing in order to confirm identification.

Some organisms are known to be ‘Gram-variable’, that is their uptake and retention of stain is not consistent.  Acinetobacter is one such organism that will sometimes appear as a gram-negative coccobacillus (see above for more details).

Short and fat Gram-negative bacilli can sometimes be mis-interpreted as cocco-bacilli, and this can include the commonly found group of ‘coliforms’. 

Gram stain interpretation is open to user variation in the descriptions used for organisms seen.  Due to their ‘in-between’ (neither coccoid or bacillary) shape and the pleomorphism that often occurs, organisms that are cocci-bacillary in nature are often subject to descriptive variation depending on the person describing them.

Additional laboratory tests available:

• Where Meningitis is suspected blood can be sent for meningococcal/pneumococcal PCR
• Where septic arthritis is suspected a synovial fluid aspirate should be obtained and sent for MC&S
• Where there is no growth on subsequent culture 16s PCR for bacterial DNA can be performed in order to identify the organism (on discussion with microbiology)

Limitations of the test:
Gram stains of positive blood culture bottles provide provisional guidance only.  They do not provide accurate identification of organisms nor do they provide susceptibilities, both of which rely on culture.  Some gram negative organisms can resist decolourisation in the staining process and as such can be mistaken for gram positive organism, whilst gram positive organisms can sometimes be over decolourised and be mistaken for gram negatives.

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Antimicrobial treatment

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