Blood Culture Identification Panel 2

(BCID2)

Guidance for Interpretation of Rapid Nucleic Acid Amplification (NAA) Blood Culture Results
1. Recommendation for Empiric Therapy Based on Nucleic Acid Amplification (NAA) Organism Detection
2. Resistance Marker Conditional Reporting
3. Gram Positive Bacteria Details
4. Gram Negative Bacteria Details
5. Yeast Details

Recommendations for Empiric Therapy

Based on Nucleic Acid Amplification (NAA) Organism Detection

ORGANISM EMPIRIC THERAPY*

Gram Positive
Staphylococcus aureus
Oxacillin or Cefazolin
mecA/C and MREJ Not Detected
Staphylococcus aureus
Vancomycin
mecA/C and MREJ Detected
Potential contaminant, particularly if 1 of 2 blood
Staphylococcal species or Staphylococcus epidermidis
culture sets; Use clinical judgement; if treatment
(not S. aureus, S. lugdunensis)
indicated, vancomycin
Enterococcus faecalis
Ampicillin
vanA/B Not Detected
Enterococcus faecium
Vancomycin
vanA/B Not Detected
Enterococcus faecalis or faecium Linezolid or Daptomycin
vanA/B Detected ID consult recommended
S. agalactiae
and/or Penicillin, Cefazolin, or Ceftriaxone
S. pyogenes
S. pneumoniae Penicillin, Ampicillin, or Ceftriaxone
Potential contaminant, particularly if 1 of 2 blood
Streptococcus species culture sets;
(not S. agalactiae, S. pyogenes, S. pneumoniae) Use clinical judgement; if treatment indicated,
ceftriaxone
Ampicillin
Listeria
ID consult recommended
 Gram Negative
Enterobacterales
E. coli
K. pneumoniae/oxytoca
Ceftriaxone
Proteus spp.
Salmonella
No Resistance Marker Detected
Enterobacterales
E. coli
K. pneumoniae/oxytoca
Meropenem
Proteus spp.
Salmonella
CTX-M Detected
Enterobacterales
Enterobacter cloacae complex
Klebsiella aerogenes Cefepime or Piperacillin/Tazobactam
Serratia marcescens
CTX-M Not Detected
Enterobacterales
Enterobacter cloacae complex
Klebsiella aerogenes Meropenem
Serratia marcescense
CTX-M Detected
Pseudomonas aeruginosa Cefepime or Piperacillin/Tazobactam
mcr-1, KPC, VIM, IMP, NDM,
Consult ID
and/or OXA-48-like Detected
Haemophilus influenzae Amp/Sulbactam or Ceftriaxone
Neisseria menigitidis Penicillin or Ceftriaxone
Stenotrophomonas maltophilia Bactrim or Ciprofloxacin
Yeast
Candida albicans
Fluconazole
Candida parapsilosis
Candida glabrata
Candida krusei Micafungin
Candida tropicalis
Cryptococcus neoformans/gattii Amphotericin B + Flucytosine
C. auris detected Consult ID and notify Infection Control
*May vary based on local antibiogram.

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 Resistance Marker Conditional Reporting
Resistance genes are conditionally reported in the BCID2 panel. The resistance marker is reported as detected or
not detected only in the case that an associated organism is detected.

Gram Positive Bacteria

Staphylococcus spp. are gram-positive cocci that are appear as irregular, clusters on a Gram stain. Staphylococcus
species are common colonizers of the skin and mucous membranes. They are opportunistic pathogens that can
cause infection following breaks in the cutaneous epithelial barrier through trauma or medical interventions.
Diagnostically, the genus is divided between coagulase-positive staphylococci and coagulase-negative
staphylococci (CoNS). Due to being commensal organisms, CoNS species are regularly isolated from clinical
specimens the provider must differentiate between contamination, colonization, and true infection
Staphylococcus aureus is capable of causing a wide range of diseases. It is estimated that approximately
40% of S. aureus isolates may be methicillin resistant (MRSA). The primary mediator of methicillin resistance
in staphylococci is the acquisition of the mecA or mecC genes encoded on the staphylococcal chromosome
cassette mec (SCCmec), a mobile genetic element that can transfer between Staphylococcus spp.
mecA/C and MREJ (MRSA) –A combined molecular detection of mecA/C, MREJ, and S. aureus indicates MRSA.
Staphylococcus epidermidis is the major cause of infections associated with prosthetic vascular grafts,
prosthetic orthopedic devices, and cerebrospinal fluid shunts.
Staphylococcus lugdunensis is part of the normal skin. It similar to S. aureus in terms of pathogenicity and
virulence. Unlike most other CoNS, S. lugdunensis remains susceptible to a wide array of antimicrobial agents,
including β-lactams.
mecA/C – indicates methicillin-resistant (MR) staphylococci (not Staphylococcus aureus). This resistance marker
will be reported with Staphylococcus epidermidis or lugdunesis.
Enterococcus faecalis and Enterococcus faecium are leading etiologies of gram-positive bloodstream infections
from urinary, intra-abdominal infections, and infectious endocarditis. While patterns of resistance may vary by
region, E. faecalis is commonly susceptible to ampicillin, while E. faecalis is more commonly resistant to this agent.
Detection of vanA/B in Enterococcus allows for rapid decision making on use of vancomycin or alternative agents
vanA/B confers vancomycin resistance in Enterococcus spp. The prevalence of vancomycin-resistant
enterococci (VRE) has increased rapidly, with VRE accounting for 60% of E. faecium and 2% of E. faecalis
isolated from the bloodstream. Enterococci carrying vanA or vanB are resistant to high levels of vancomycin.
Streptococcus spp. are gram-positive cocci that appear in chains or pairs on a Gram stain. Streptococcus species
are frequently found as commensal bacteria on mucous membranes and are occasionally present as transient
skin microbiota.

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 Streptococcus agalactiae (Group B Streptococcus) can cause both early-onset neonatal disease, characterized
by sepsis and pneumonia within the first seven days of life, and late-onset disease with meningitis and
sepsis between day seven and three months of age. In adult patients, the spectrum of S. agalactiae infections
includes blood-stream infection (BSI), pneumonia, meningitis, and endocarditis.
Streptococcus pneumoniae colonizes the upper respiratory tract and is the most frequently isolated respiratory
pathogen in community-acquired pneumonia.
Streptococcus pyogenes (Group A Streptococcus) colonizes the human skin and upper respiratory tract, with
these sites serving as primary focal sites of infections and principal reservoirs of transmission of these gram-
positive bacteria.
Listeria monocytogenes, the causative agent of listeriosis, is a gram-positive bacillus that is ubiquitous in soil and
water and can be found in the gastrointestinal tract of up to 5% of healthy adults. Listeriosis is considered the
most severe bacterial foodborne infection due to its high mortality rate, despite early antibiotic treatment (11 –
60%). Populations at risk for developing invasive listeriosis include the immunosuppressed, pregnant women,
neonates, fetuses, and the elderly.
Gram-Negative Bacteria
Acinetobacter calcoaceticus-baumannii complex organisms (A. baumannii, A. calcoaceticus, A. dijkshoorniae, A.
nosocomialis, A. pittii, and A. seifertii) are related Acinetobacter species not reliably differentiated from one another by
some manual or automated phenotypic microbial identification systems. These organisms are ubiquitous, non-
fermentative, and gram-negative coccobacilli that primarily act as opportunistic pathogens infecting critically ill
patients. Multi-drug resistant strains demonstrate resistance to most antibiotic classes, including carbapenems.
Bacteroides fragilis is an obligately anaerobic, gram-negative, non-spore-forming rod. Bacteroides species, of which
B. fragilis is the most common, are part of the normal microbiota of the human colon. However, they can cause
significant infection if displaced into the bloodstream or surrounding tissue.
Enterobacterales is an order composed of seven families (Budviciaceae, Enterobacteriaceae, Erwiniaceae, Hafniaceae,
Morganellaceae, Pectobacteriaceae, and Yersiniaceae), many genera, and over 250 species of gram-negative,
facultatively anaerobic rods and coccobacilli. The spread of antimicrobial resistance in Enterobacteriaceae has
increased the complexity of treating BSI associated with the gram-negative bacteria. Resistance to third- and
fourth-generation cephalosporins is mediated primarily by the production of extended-spectrum β-lactamases
(ESBLs) and overproduction of AmpC β-lactamases. While the majority of Enterobacteriaceae remain
susceptible to carbapenems, KPC-type carbapenemases are emerging and spreading (carbapenem-resistant
Enterobacteriaceae; CRE) in certain locations within the United States and worldwide.
Enterobacter cloacae complex organisms (E. cloacae, E.asburiae, E. hormaechei, E. kobei, E. ludwigii, and E. mori)
are gram-negative, rod-shaped bacteria. E. cloacae complex organisms have been implicated in numerous
nosocomial infections.
Escherichia coli are gram-negative bacteria that are part of the normal flora of the intestines of humans
and animals. Most pathogenic E. coli infections are associated with gastrointestinal illness, but may also
cause urinary tract infections, BSIs, and meningitis. As with other Enterobacteriaceae, extended-spectrum
β-lactamases (ESBLs), including CTX-M and AmpC β-lactamases, and Klebsiella pneumoniae-carbapenemase
(KPC) pose a significant antibiotic resistance problem.
Klebsiella aerogenes, previously known as Enterobacter aerogenes, is a gram-negative, facultatively anaerobic,
rod-shaped bacterium. It is a nosocomial and opportunistic pathogen generally found in the gastrointestinal
tract, urine, and skin of colonized patients.
Klebsiella oxytoca is an aerobic gram-negative, rod-shaped bacterium that is carried on mucosal surfaces
(nasopharynx and bowel) and found in agricultural environments. Opportunistic infections due to K. oxytoca
include soft tissue infections, urinary tract infections, pneumonia, and BSIs.
Klebsiella pneumonia group includes three phylogroups classified as distinct species; K. pneumoniae, K.
quasipneumoniae, and K. variicola. K. pneumoniae is associated most often with nosocomial infections in the
elderly or immunocompromised.

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 Proteus spp. are commonly isolated, with Proteus mirabilis observed most frequently. Most infections
(approximately 85%) are thought to be community acquired; however, nosocomial outbreaks have also
occurred.
Salmonella spp. are motile, gram-negative, facultatively anaerobic rods that are associated with infection
following the consumption of contaminated meat, fresh produce, and manufactured products. Strains of
Salmonella are categorized as typhoidal and non-typhoidal.
Serratia marcescens is a common nosocomial pathogen and colonizer. S. marcescens is the primary pathogenic
species of the Serratia genus. It is of particular concern due to its emerging antibiotic resistance to commonly
used agents like β-lactams, aminoglycosides, carbapenems, and fluoroquinolones.
Pseudomonas aeruginosa is an opportunistic, gram-negative pathogen that rarely causes disease in healthy
individuals but can cause sepsis in patients with burn wounds, malignancies, immunodeficiency, or in preterm
infants. P. aeruginosa is a leading cause of nosocomial infections and is responsible for 10% of all hospital-
acquired infections. P. aeruginosa is susceptible to a limited number of antibiotics (antipseudomonal penicillins and
cephalosporins, carbapenems, fluoroquinolones, and ciprofloxacin), and multi-drug resistant (MDR).
CTX-M is a class A extended-spectrum β-lactamase (ESBL) resistance enzyme. CTX-M ESBLs are predominantly
found in the Enterobacteriaceae family. However, they have also been reported in other non-enteric, gram-
negative bacteria such as Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Acinetobacter baumannii, Vibrio
spp. and Aeromonas spp. Over the last decade, CTX-M has become the most prominent ESBL in the United States.
Carbapenemase Genes (IMP, KPC, NDM, VIM, OXA-48-like) confer resistance to beta-lactam antibiotics
including cephalosporins and carbapenems. Depending on the resistance marker detected, some of the new
beta-lactam/beta-lactamase inhibitor combos may also be clinically ineffective. Treatment with ceftazidime-
avibactam or meropenem-vaborbactam is recommended when KPC and/or OXA-48-like markers are detected.
Detection of IMP, NDM, and/or VIM may necessitate combination treatment. Consultation with an ID physician
and/or pharmacist are recommended in the event any of these markers are detected.
mcr-1 is an emerging marker of public health importance. It is associated with elevated MICs to colistin, a last-
resort drug for some multidrug-resistant infections.
Haemophilus influenzae is a gram-negative coccobacillus, isolated exclusively from humans, that can be present
as normal flora of the oropharynx and can cause infections when introduced into the lower respiratory tract.
Approximately 20-35% of isolated strains are resistant to amoxicillin.
Neisseria meningitidis is a fastidious, aerobic, gram-negative diplococcus that is spread by mucus or respiratory
droplets, often from asymptomatic carriers. This organism may progress quickly and is associated with BSI and
meningitis with fever and a characteristic hemorrhagic rash.
S. maltophilia can infect both children and adults. Hospital-acquired infections associated with substantial
morbidity and mortality are increasing, particularly in the immunocompromised patient population. In addition,
community-acquired S. maltophilia infections have been reported from patients that often presented some form of
comorbidity (trauma, central venous catheter, prior antibiotic use, malignancy, HIV infection, etc.). S. maltophilia is
intrinsically resistant to multiple classes of antibiotics.
Yeast
Candida species are yeasts that are ubiquitous in the environment and as members of the normal human
microbiota, especially in the digestive tract and on mucous membranes. These fungi are important agents of
opportunistic nosocomial infections ranging from superficial (e.g. oral thrush) to systemic (e.g. BSI). They often
occur in combination with other bacteria or a second Candida spp. The five most common species causing
BSIs are C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei. C. albicans accounted for over 65%
of all Candida BSI cases reported in North America. Among the non-C. albicans species, C. glabrata is the most
common cause of BSI in the United States, while C. parapsilosis and C. tropicalis are the major players in other
countries. Candida krusei is well known as a fungal pathogen among patients with hematologic malignancies and
among blood and marrow transplant recipients.

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 Candida auris was first reported in 2009 as an isolate from the external ear canal of a patient from Japan. This
report was followed by the first three cases of nosocomial BSI caused by C. auris in 2011 from South Korea. A
collaborative project led by the US Centers for Disease Control and Prevention (CDC) described the multidrug-
resistant (MDR) nature of C. auris and its global emergence as a nosocomial pathogen: 93% of the 54 isolates
from this study were reported to be resistant to fluconazole, the standard antifungal drug of choice in many
countries, 41% were resistant to two antifungal classes, and 4% were resistant to three classes.
Cryptococcus neoformans/gattii are fungi found in soil and bird droppings that can become pathogenic
following their inhalation and hematogenous spread to the brain and meninges. C. neoformans is considered an
opportunistic pathogen of immunocompromised individuals. It is the AIDS-defining illness in up to 50% of AIDS
patients. C. gattii infections are relatively rare but appear to be increasing. In addition to those with reduced
immune function, C. gattii can also cause disease in the immunocompetent, particularly in persons with underlying
health conditions.
Information above adapted from the Instruction for Use from BioFire Diagnostics Blood Culture Identification Panel 2

HNL07.006 © HNL Lab Medicine 2021

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