Guideline for Antibiotic Management Based on Rapid Diagnostic Blood Culture Results in Adult and Pediatric Patients

Modified Date: 
December 14, 2020

 

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.

1.1

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
(includes cultures from other facilities outside UCSF)

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:

 

1.2

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

 

 

1.3

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.

 

1.4 

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)

Vancomycin

 

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 if further assessment is desired.

 

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

Ampicillin

 

 

 

 

Ampicillin

 

 

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

  • Preferred, unless high-risk drug interactions with serotonergic meds

 

2nd line: Daptomycin^

  • Consider for patients with high-risk serotonergic drug interactions
  • Do not use daptomycin if concerned for pulmonary infection

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

Vancomycin

 

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.

 

1.5

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:  

  • Start or continue an antimicrobial with activity against coagulase-negative staphylococci based on mecA status, as defined in Section 1.4 above [online: link to section].
  • Repeat two sets of blood cultures (before new antimicrobial is added, if not started initially)

 

If patient has implanted prosthetic material:

  • Consider ID consult

 

If repeat cultures are positive for the same species of coagulase-negative staphylococcus:

  • Continue directed therapy against coagulase-negative staphylococcus

 

If repeat cultures are positive for a different species of coagulase-negative staphylococcus:

  • Discontinue therapy, as this likely represents contamination

 

If repeat cultures are negative and the patient is hemodynamically UNSTABLE:

  • Continue current antimicrobial and consider ID consult

If patient is hemodynamically STABLE and does NOT have implanted prosthetic material:

  • Discontinue or do not start Gram-positive antimicrobial
  • Consider repeating two sets of blood cultures if still concerned for a bloodstream infection

If repeat blood cultures are positive for the same species of coagulase-negative staphylococcus:

  • In some cases, this is more consistent with a true bloodstream infection. Re-start Gram-positive antimicrobial or consult ID/ASP if additional guidance is desired.

 

If repeat cultures are positive for a different species of coagulase-negative staphylococcus:

  • Discontinue therapy, as this likely represents contamination

 

If repeat blood cultures are negative:

  • Discontinue Gram-positive antibiotic (if not already)

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.

 

 

 

1.6

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

 

1.7

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.