The Case

75 yo female, multiple medical problems presents with subjective fever/cough for 2 days.  Work-up shows – nml VS, lactate 1 and left lower lobe infiltrate.  Unfortunately she’s CURB-65 of 2 (age and BUN) with PORT score of 95.  More importantly she lives by herself and doesn’t seem altogether reliable.  Plan: ceftriaxone/azithromycin for CAP and admit.  Med Senior later informs you that…….YOU FORGOT THE BLOOD CULTURES!!!!! And the patient already got antibiotics!!! WHAT HAVE YOU DONE!?!?!!

Don’t worry, only CMS (Centers for Medicaid and Medicare Services) and IDSA and American Thoracic Society and JCAHO and Surviving Sepsis Guidelines recommend/require two sets of blood cultures prior to antibiotics for anyone admitted for pna.

        But what is the evidence for this?
To start, two studies reviewed all undifferentiated blood cultures.  One study yielded only 1.4% of true positive blood cultures  with 0.18% affecting patient management.  The other study yielded 5% true positives with 1.6% affecting patient management.  Of these 1.6% (18), 9 were septic, 8 had fever with active cancer, and 1 had pneumonia.  By combing these studies we find a 0.7% chance of affecting patient care.  That’s a NNT of 143!  Additionally, patients with false positive cultures had significantly longer length of stays leading to increased cost.

            Now, what about our patient with pneumonia?

Benenson et al.

This study retrospectively reviewed 684 patient charts with ED blood cultures and a discharge diagnosis of pneumonia.  They found 23 (3.4%) true positive and 54 (7.8%) false positives.   Of these 23 patients, 3 had their antibiotic regiment narrowed without anyone needing broader coverage.  That’s a 0.4% chance of a blood culture drawn affecting patient management, or an NNT of 250!  Oddly, 18 additional patients could have been narrowed based on culture results, but were not.

Positive blood culture was associated with: RR>30 (OR 3.7), Na< 130mm/L (OR 5.72), and active chemotherapy (OR 4.59).  An O2sat < 90% (OR 2.41) was statistically significant initially, but not with logistic regression analysis.

            They recommend “eliminating blood cultures for CAP patients and obtaining blood cultures for HCAP patients presenting to the ED”

Kennedy et al

Of 414 ED blood cultures drawn for pneumonia, 29 (7%) were true positives and 25 (6%) false positives/contaminants.  Of the 29 true positives, 11 (2.7%) had their coverage narrowed, 4 (1%) had their coverage broadened, and another 8 could have been narrowed based on culture results but were not.  In this study, the rate of blood culture affecting patient care was higher at 3.6%.  Oddly, 3 of the 4 that needed broader coverage were from a nursing home, had MRSA, but had not been initially treated with HCAP regiments.

Coburn et al.

A lit search/meta-analysis that investigated probability of bacteremia in immune-competent patients without suspicion for endocarditis.  They divided the patients into three groups based on their risk of having a positive blood culture.  They did not recommend a blood culture in the Low risk group due to the low pre-test probability of a true positive culture – which they described as anything less than 14%.  This group included ambulatory outpatients, cellulitis, patients admitted for CAP, or fever from the community.

They recommended blood cultures in both the Intermediate and high risk group with 19-25% and 38-68% chance of true positive blood culture respectively.  The intermediate risk group included only pyelonephritis and the high risk included included severe sepsis, septic shock, and bacterial meningitis.

In terms of risk factors for a true positive culture, the following were NOT statistically significant: subj fever, tachycardia alone, elevated wbc count, fever.

The following were statistically significant: shaking chills, hypotension, needing pressors, neurtrophil/lymphocyte ratio > 10, presence of SIRSS.  Interestingly, having zero SIRSS criteria had a LR 0.09 for a true positive culture.

The Shapiro study:

Prospective analysis of 3,730 pneumonia patients with blood culture drawn in ED or up to 3 hours after admission.

In the derivation population, they found a statistically significant increased risk of positive blood culture in the characteristics listed below.  After some moderately complicated calculations, they created Major Criteria and Minor Criteria and recommended a blood culture only if the patient has one major or two minor criteria

Major Criteria

Suspected endocarditis

Temp > 103

Indwelling vascular catheter

  Minor Criteria

Temp >101

Age >65

Chills

Vomiting

SBP< 90

WBC >18k

Bands > 5%

Plts< 150,000

Cr > 2.

This system has a negative predictive value for a true positive blood culture of 99.4% (95% CI 99-100%) and 99.1 % (95% CI 98-100%) in the derivation group and validation group respectively.  Seven total patients in the validation group were missed by the decision rule.  Of those, five would have had no change in management, one should have received a culture by the prediction rule but was missed in the ED, and one received a blood culture for a fever > 3 hours after admission.  In my opinion, none of these failed the decision rule itself in terms of predicting when a blood culture will affect patient management.

So what does CMS actually say?

http://www.qualitymeasures.ahrq.gov/content.aspx?id=35525

US department of Health and Human Services

IDSA and ATS guidelines for CAP…recommend that pretreatment blood samples for culture should be obtained from hospitalized CAP patients who are

admitted to the intensive care unit (ICU)

-have cavitary infiltrates

-leukopenia, chronic severe liver disease

-asplenia

-plural effusion

– have a positive pneumococcal urinary antigen test (UAT)

– have active alcohol abuse (Mandell, 2007)

EXTRA BONUS SECTION!?!?!?!

If you are going to do cultures, the literature emphasizes that volume matters.  You have a 3% increased yield in positive blood cultures per ml you put in.  Most recommend at least 7ml per blood culture bottle.

What about culturing them the second you find out they are febrile? What is the best time to culture a patient?  The data shows: 1-2 hours before the fever happens.  Good luck with that.  Multiple studies have shown no significant difference in results if the patient is cultured at Tmax, vs hours before vs hours after.  According to this data, you don’t need to rush to do abx when someone is febrile especially because another fun study showed contaminated blood culture rates increased linearly with increased patient load in the ED.

Conclusions

–     Per multiple national guidelines you are supposed to get a blood culture for CAP. 

–    Cultures rarely affect management, but are recommended by the literature when certain criteria are met including sepsis, endocarditis, and others listed above.

–    If you are going to get one: clean well, don’t hurry, don’t worry about when the patient is febrile, and fill up the blood culture bottles with at least 7ml each. 

 What do y’all think?

Special thanks to Dr. Jackie Shibata for initiating the clinical question and for her generally being a wonderful person.

 References

Mermel et al.  Detection of bactermia in adults: consequences of culturing an inadequate volume of blood Ann Intern Med. 1993;119:270-272

Riedel et al.  Timing of Specimen Collection for Blood Cultures from Febrile Patients with Bacteremia. Journal of Clinical Microbiology, Apr 2008 p 1381-1385

Halverson et al. Impact of Hourly Emergency Department Patient Volume on Blood Culture Contamination and Diagnostic Yield. Journal of Clinical Microbiology June 2013 vol 51, number 6.

Benenson et al. Selective Use of Blood Cultures in Emergency Department Pneumonia Patients. Journal of Emergency Medicine, vol 33, No. 1 pp 1-8 2007

Coburn et al.  Does This Adult Patient With Suspected Bacteremia Require Blood Cultures. Jama, Aug 2012 – vol 308, no 5

Kennedy et al. Do Emergency Department Blood Cultures Change Practice in Patients with Pneumonia? Annals of Emerg Med, Volume 46, No. 5: Nov 2005

Shapiro et al. Who Needs a Blood Culture? A Prospectively Derived and Validated Prediction Rule, J of Emerge Med Vol 35, no.3. pp255-264, 2008

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1 Comment

ericcioe · January 17, 2014 at 3:49 pm

Andy,
One of the crazy things about the CME policy if you read the exclusion criteria carefully is that it only applies if cultures are drawn during the inpatient stay. In other words, if you never draw cultures, the rule doesn’t apply. The hospital is only penalized if the cultures are drawn after antibiotics are given so it doesn’t apply if no one ever draws cultures and feels they aren’t indicated. This is interesting because it could spur discussions with our inpatient colleagues about possibly forgoing the blood cultures for simple CAP that require inpatient admission but in whom antibiotic coverage will not be narrowed, and there is no suspicion of severe sepsis or septic shock.

Food for thought.

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