Content Guide
When should I consult Infectious Diseases about a positive blood culture?
When can I expect updated or final results on this blood culture?
Should I make changes in therapy based on the blood culture Gram stain?
What is mecA? vanA? vanB? How should I interpret this information?
How can I figure out if this blood culture is true positive vs. a contaminant?
What are “preliminary susceptibilities”? Should I make antibiotic changes based on them?
These guidelines inform selection and modification of antibiotic therapy based on preliminary blood culture results. They are not intended to replace clinical judgement. Modification of therapy may be indicated based on patient comorbidities, previous antibiotic therapy, or infection history. These guidelines apply to patients at UCSF Medical Center and UCSF Benioff Children’s Hospital San Francisco who have positive blood culture results from the UCSF Clinical Microbiology Laboratory.
Infectious Diseases Consultation for Patients with Positive Blood Culture Results
Infectious Diseases consultation is required for some patients with positive blood culture results and is encouraged for other situations when the clinical team believes that consultation would be helpful.
|
Location |
Positive blood culture for Staphylococcus aureus (including cultures from other facilities outside UCSF) |
Positive blood culture with another organism or preliminary |
|
UCSFMC Parnassus, Mount Zion, or Mission Bay Adult Services |
Consult to Adult Infectious Diseases service required |
Consult at the discretion of primary clinical team. Reasons for consultation may include but are not limited to complicated infection, delayed clearance of cultures, antimicrobial allergies, or the presence of multidrug resistant organisms. |
|
UCSF BCH San Francisco |
Consult to Pediatric Infectious Diseases service required |
Consult to Pediatric Infectious Diseases service required |
The Antimicrobial Stewardship Team (Adult ASP at Parnassus, Pediatric ASP at Mission Bay) is available during daytime hours on weekdays for focused consultation, interpretation of results, and therapeutic recommendations for patients who are not actively followed by an ID consult team. When either ID consult or ASP is readily available, they should be the primary resource for questions regarding interpretation of preliminary blood culture results.
Exceptions to this general guideline should be considered for:
- Infections that are likely to be polymicrobial (e.g. intra-abdominal source)
- Multiple types of bacteria reported on Gram stain or culture (e.g. Gram-negative rods and Gram-positive cocci)
- Patients with febrile neutropenia, though de-escalation is encouraged if deemed clinically appropriate per UCSF Guidelines for Inpatient Management of Febrile Neutropenia in Adults and UCSF Management of Fever in Pediatric Oncology and BMT Patients
- Patients receiving antimicrobial therapy for another concurrent microbiologically or clinically documented infection
- Decompensating patients who are undergoing further microbiologic evaluation with additional cultures collected
Reporting Timeline for Species Identification and Susceptibilities:
|
Time from Positive Blood Culture |
Result Available to Clinical Team |
Additional Explanation |
|
1-2 hours |
Gram stain |
See Section 1.3 |
|
2-8 hours |
Gram-positive organism identification and resistance mechanism, inpatient only |
Verigene results of Gram-positive organisms only; see Section 1.4 |
|
12- 15 hours |
Gram-negative preliminary susceptibilities reported |
Disk diffusion results for Gram-negative organisms; see Section 1.6 |
|
24-48 hours |
Definitive organism identification |
MALDI-TOF results confirming Verigene results for Gram-positive organisms or new identification for Gram-negative organisms |
|
48-72 hours |
Definitive susceptibility results |
Traditional susceptibility testing to confirm Verigene resistance mechanisms for Gram-positive organisms and disk diffusion results for Gram-negative organisms; see Section 1.7 |
Gram Stain Results:
Gram stain results are available upon notification of positive blood culture. In general, antibiotic therapy directed against Gram-negative organisms should be discontinued if the blood culture shows a Gram-positive, non-contaminant pathogen (and vice versa); exceptions to changing therapy should be considered for certain infection-specific and patient-specific characteristics listed here.
Verigene Gram-Positive Panel Result Interpretation for Treatment Recommendations:
Below are general recommendations based on our hospital-specific antibiogram, medication formulary, and Verigene performance characteristics. These recommendations are not intended to replace clinical judgement.
Verigene Gram-Positive Blood Culture Panel (BC-GP) Performance Characteristics
The Verigene assay is an FDA-approved nucleic acid test that identifies twelve Gram-positive organisms and two antibiotic resistance markers (mecA = methicillin resistance; vanA/vanB = vancomycin resistance) directly from blood samples. This assay demonstrates excellent concordance with traditional susceptibility methods.
|
Resistance Marker |
Organism |
Sensitivity: Verigene BC-GP concordance with conventional methods for the detection of resistance markers % (nVerigene / n conventional) |
Specificity: Verigene BC-GP concordance with conventional methods for the absence of resistance markers % (nVerigene / n conventional) |
|
MecA |
Staphylococcus aureus (n=335)* |
97.5% (157/161) |
98.8% (172/174) |
|
Staphylococcus epidermidis (n=330)⁺ |
92.0% (219/238) |
81.5% (75/92) |
|
|
VanA |
Enterococcus faecalis (n=109)^ |
85.7% (12/14) |
100% (95/95) |
|
Enterococcus faecium (n=114)# |
97.2% (69/71) |
93.0% (40/43) |
|
|
VanB |
Enterococcus faecalis (n=109)^ |
100% (7/7) |
100% (102/102) |
|
Enterococcus faecium (n=114)# |
97.0% (32/33) |
100% (81/81) |
*For Staphylococcus aureus isolates, Verigene BC-GP correctly identified the presence of the mecA gene in 97.5% of isolates that were later identified as methicillin-resistant using conventional biochemical methods (culture and cefoxitin disk diffusion). Verigene BC-GP did not identify mecA in 98.8% of Staphylococcus aureus isolates that were later identified as methicillin-susceptible by conventional methods.
⁺For Staphylococcus epidermidis isolates, Verigene BC-GP correctly identified the presence of the mecA gene in 92% of isolates that were later identified as methicillin-resistant using conventional biochemical methods (culture and cefoxitin disk diffusion). Verigene BC-GP did not identify mecA in 81.5% of Staphylococcus epidermidis isolates that were later identified as methicillin-susceptible by conventional methods.
^For Enterococcus faecalis isolates, Verigene BC-GP correctly identified the presence of the vanA or vanB genes in 85.7% and 100% of isolates, respectively, that were later identified as vancomycin-resistant using conventional biochemical methods (culture and bidirectional sequencing). Verigene BC-GP did not identify vanA or vanB in 100% and 100% of isolates, respectively, that were later identified as vancomycin-susceptible by conventional methods.
#For Enterococcus faecium isolates, Verigene BC-GP correctly identified the presence of the vanA or vanB genes in 97.2% and 97% of isolates, respectively, that were later identified as vancomycin-resistant using conventional biochemical methods (culture and bidirectional sequencing). Verigene BC-GP did not identify vanA or vanB in 93% and 100% of isolates, respectively, that were later identified as vancomycin-susceptible by conventional methods.
Limitation of the Verigene Gram-Positive Panel (BC-GP):
- In mixed cultures containing Gram-positive bacteria and other organisms, BC-GP may not identify all the detectable organisms in the specimen. For these reasons, Verigene results should always be confirmed with final organism identification and susceptibilities.
- Verigene only identifies vancomycin resistance mediated by vanA/vanB. While these are the most common causes of vancomycin resistance amongst enterococci, vancomycin resistance can be caused by genes other than vanA and vanB.
- There is a risk of false positive results due to cross-contamination by target bacteria and their nucleic acids.
- The assay detects the presence of resistance genes (e.g. mecA and vanA/vanB), but does not determine which organisms produced the gene.
For more information on the Verigene Assay Test Characteristics, please consult the package insert.
Verigene results are available within 2-8 hours of the first positive blood culture. These results will only be reported for inpatients or ED patients if the initial Gram stain shows a Gram-positive organism. While the recommendations below address the most common results, additional Gram-positive organisms may be identified. The ASP teams may be contacted with questions regarding result interpretation and therapy selection. Exceptions to changing therapy based on Verigene results should be considered for certain infection-specific and patient-specific characteristics listed here.
|
Verigene Gram-Positive Panel Result |
Interpretation |
Treatment Recommendation* |
Comments |
|
Staphylococcus aureus mecA detected |
Methicillin-resistant Staphylococcus aureus (MRSA) |
If allergy/intolerance to vancomycin: consult ID |
We recommend ID consult for all patients with S. aureus bacteremia.
|
|
Staphylococcus aureus mecA not detected |
Methicillin-susceptible Staphylococcus aureus (MSSA) |
STOP vancomycin and START cefazolin (preferred) OR nafcillin
Use nafcillin if meningitis suspected or in preterm neonate
If beta-lactam allergy: refer to UCSF Beta-Lactam Allergy Guideline |
We recommend ID consult for all patients with S. aureus bacteremia.
Vancomycin is inferior to cefazolin/nafcillin for MSSA treatment
|
|
Staphylococcus epidermidis mecA detected |
Methicillin-resistant Staphylococcus epidermidis |
If treatment indicated: vancomycin
If allergy/intolerance to vancomycin: consult ASP or ID |
Frequent contaminant; see Section 1.5 below titled “Assessing for Blood Culture Contamination” |
|
Staphylococcus epidermidis mecA not detected |
Methicillin-susceptible Staphylococcus epidermidis |
If treatment indicated: STOP vancomycin and START cefazolin (preferred) OR nafcillin
Use nafcillin if meningitis suspected or in preterm neonate
If beta-lactam allergy: refer to UCSF Beta-Lactam Allergy Guideline |
Frequent contaminant; see Section 1.5 below titled “ Assessing for Blood Culture Contamination”
|
|
Staphylococcus lugdunensis
Note that the presence of mecA will NOT be detected for this species |
Staphylococcus lugdunensis |
If treatment indicated: vancomycin
If allergy/intolerance to vancomycin: consult ID |
Although S. lugdunensis is a type of coagulase-negative Staphylococcus, it tends to be more pathogenic. Consult ID generally recommended.
If methicillin susceptibility is confirmed by conventional testing, STOP vancomycin and START cefazolin (preferred) OR nafcillin.
Use nafcillin if meningitis suspected or in preterm neonate |
|
Enterococcus faecalis vanA OR vanB detected
OR
vanA AND vanB not detected |
Vancomycin-resistant Enterococcus faecalis
OR
Vancomycin-susceptible Enterococcus faecalis |
If beta-lactam allergy: refer to UCSF Beta-Lactam Allergy Guideline |
At UCSF, all E. faecalis bloodstream isolates in recent years have been ampicillin-susceptible, including the low number of vancomycin-resistant isolates
ID consult recommended for all VRE bloodstream infections in adult patients, especially if suspected/confirmed endocarditis.
|
|
Enterococcus faecium vanA detected OR vanB detected |
Vancomycin-resistant Enterococcus faecium |
1st line: Linezolid
2nd line: Daptomycin^
|
ID consult recommended for all VRE bloodstream infections in adult patients, especially if suspected/confirmed endocarditis.
Consult clinical pharmacist regarding drug interaction assessment |
|
Enterococcus faecium vanA not detected AND vanB not detected |
Vancomycin-susceptible Enterococcus faecium |
If allergy/Intolerance to vancomycin: consult ASP or ID
|
If ampicillin susceptibility is confirmed by conventional testing, STOP vancomycin and START ampicillin.
If suspected/confirmed endocarditis, ID consult recommended |
|
Other result |
Mixed culture (containing >1 organism)
Panel also detects Streptococcus agalactiae (GBS), Streptococcus anginosus group, Streptococcus pneumoniae, Streptococcus pyogenes (GAS), Listeria species, and may result with Staphylococcus or Streptococcus genus without species detected |
Contact ID or ASP for guidance or modify therapy according to detected organism and anticipated susceptibility |
|
*Refer to Antimicrobial Dosing Guidelines
^These antibiotics are restricted and require prior authorization from the ASP or ID team:
- During daytime hours:
- For adult patients: Antimicrobial Stewardship Pharmacist Pager or Antimicrobial Stewardship Pharmacist on Voalte
- For BCHSF/pediatric patients: Pediatric ID/ASP Pharmacist or Pediatric ID/ASP Provider on Voalte, or page Pediatric ID Consult team.
- After hours: Verifying pharmacist will approve a one-time dose overnight; page appropriate ASP/ID point-of-contact listed above the next day for continued approval.
Assessing for Blood Culture Contamination:
Roughly 50% of blood cultures may grow organisms not truly representing bacteremia, referred to as contaminants. Coagulase-negative staphylococci (e.g. Staphylococcus epidermidis group) are the most common blood culture contaminants. If the patient is clinically stable with low pretest probability for bloodstream infection (e.g. lack of central venous catheter or endovascular prosthetic material), antibiotics may not be indicated for all blood cultures growing coagulase-negative staphylococci.
The following practices may minimize contamination, or maximize the ability to recognize contamination:
- Draw at least 2 blood cultures at the same time (3 cultures are recommended for suspected sepsis).
- Draw each set of cultures from multiple venipuncture sites.
- Avoid drawing cultures from a peripheral venous or arterial catheter as these are associated with higher rates of contamination.
- Use time to positivity to assess likelihood of true vs. false positive. For example, a culture is more likely to represent a true pathogen if it is reported positive in <24 hours versus 3 days.
A provider may opt to conservatively treat a possible blood culture contaminant with antibiotics in certain situations based on lack of diagnostic certainty and/or relative patient risk for complications. If patient-specific evaluation is desired, then ID consultation should be requested.
The following algorithm provides guidance for interpreting a possibly contaminated blood culture:
|
Organism Identification (by Verigene or MALDI-TOF) |
Recommended Action(s) |
Recommended Action Following Repeat Cultures (if applicable) |
|
1 out of 2 blood cultures or 1 out of 1 blood cultures with coagulase-negative staphylococcus
|
If patient is hemodynamically UNSTABLE OR has implanted prosthetic material:
|
If patient has implanted prosthetic material:
If repeat cultures are positive for the same species of coagulase-negative staphylococcus:
If repeat cultures are positive for a different species of coagulase-negative staphylococcus:
If repeat cultures are negative and the patient is hemodynamically UNSTABLE:
|
|
If patient is hemodynamically STABLE and does NOT have implanted prosthetic material:
|
If repeat blood cultures are positive for the same species of coagulase-negative staphylococcus:
If repeat cultures are positive for a different species of coagulase-negative staphylococcus:
If repeat blood cultures are negative:
|
|
|
2 out of 2 blood cultures with the same coagulase-negative staphylococcus
|
In some cases, this is more consistent with a true bloodstream infection. However, this scenario could still represent contamination.
Use clinical judgement to determine the need for antimicrobial therapy pending definitive biochemical identification or contact ASP/ID for additional guidance. |
|
Preliminary/Direct Susceptibility by Disk Diffusion (Kirby-Bauer) Susceptibility on Gram Negative Organisms:
For Gram-negative organisms, preliminary susceptibility results from disk diffusion will appear in the chart ~12-24 hours from positive blood culture. Based on available literature, disk diffusion results have >95% concordance with final susceptibilities attained via broth microdilution applying standard breakpoints. The likelihood of falsely concluding susceptibility to an antibiotic based on these results is <1.5% across multiple studies. Disk diffusion results will not show a numerical minimum inhibitory concentration, but will report a sensitive or resistant interpretation. The UCSF Clinical Microbiology Laboratory will not report preliminary results that are in the intermediate range. We recommend that clinicians use these preliminary susceptibility results to modify antibiotic selection (see table below). Exceptions to changing therapy based on disk diffusion results should be considered for certain infection-specific and patient-specific characteristics listed here.
Interpretation and Treatment Recommendations for Gram-Negative Preliminary Susceptibilities
|
Preliminary Susceptibility Result |
Interpretation |
Treatment Recommendation |
Comments |
|
Ertapenem-sensitive, without other preliminary susceptibilities reported |
Possible ESBL-producing Gram-negative organism |
Start or continue a carbapenem antibiotic |
If beta-lactam allergy: refer to UCSF Beta-Lactam Allergy Guideline |
|
Other antibiotic susceptibility results reported
|
Gram-negative organism is susceptible to the reported antibiotics |
In most situations, it is appropriate to de-escalate antibiotics based on the preliminary susceptibility results
In certain clinical situations, it is reasonable to continue broader antibiotics while obtaining additional data |
If beta-lactam allergy: refer to UCSF Beta-Lactam Allergy Guideline |
Final Susceptibilities:
Final susceptibilities for both Gram-positive and Gram-negative organisms are typically available ~48-72 hours from positive blood culture. These results should always be reviewed. In most cases, the narrowest, most effective antibiotic should be selected to complete the course of therapy. There may be opportunities to refine antimicrobial treatment based on the final susceptibility results.