We next compared data associated with Gram-positive vs. Gram-negative organisms. Gram-negative bacteremia occurred in older patients (66.5 ± 1.8 years vs. 59.9 ± 1.4 years; P = 0.0104) and was associated with higher WBC count (16,700 ± 900 μl vs. 14,200 ± 500 μl) and percentage neutrophils (86.9 ± 0.8% vs. 83.5 ± 0.7%; P < 0.05 in each case), as well as higher absolute neutrophil count (14,500 ± 800 μl vs. 12,100 ± 500 μl; P < 0.01).
We next generated odds ratios (OR) for bacteremia in patients with a clinical indication for obtaining blood culture. The OR for varying levels of leukocytosis, neutrophilia, and bandemia by univariate analysis are shown (Table 3). Increasing WBC count was associated with increasing OR of bacteremia (3.16 at ≥12,000 μl vs. 5.88 at ≥20,000 μl). Neutrophilia was also predictive of bloodstream infection (OR 3.17–4.16). Bandemia was highly correlated with bacteremia, particularly when band cells represented at least 10% of the total neutrophil count (OR 7.89). In multivariate analysis, leukocytosis and/or neutrophilia correlated with increased incidence of bacteremia. Advanced age and female gender were modest risk factors for bacteremia.
We finally analyzed patients in each of 3 categories (Table 4): presence or absence of WBC count ≥ 12,000 μl, percent neutrophils ≥ 80%, and band neutrophils ≥ 5%. When none of these criteria were present, 11.2% of blood cultures were positive (OR = 0.086), constituting the low-risk category. When all 3 criteria were present, 75% of patients had bloodstream infections (OR = 4.25), constituting the high-risk category (RR = 49.5 vs. all negative criteria). When only 1 of the 3 criteria were present, culture-positivity ranged from 25% to 47.5% (OR = 0.43–1.24; RR = 5.0–14.4), with neutrophilia the most important predictor. When 2 of the 3 criteria were present, culture positivity ranged from 53.3% to 61.3% (OR = 1.7–3.92; RR = 19.8–45.6).
In this report, we show that data obtainable on a CBC are predictive of blood culture positivity. Leukocytosis, neutrophilia, and bandemia are reliable indicators of bloodstream infection. We placed patients in risk categories based on WBC count ≥ 12,000 μl, neutrophilia ≥ 80%, and bandemia ≥ 5%. These cutoffs provided the best discrimination between positive and negative cultures in our data set. When none of these criteria are present, the likelihood of bloodstream infection is low and clinicians may choose to defer blood culture in favor of observation. When all 3 are present, the likelihood of bloodstream infection is significant (ie, nearly 50-fold greater than when the above CBC parameters are normal) and blood culture is likely to have high yield. Clinical judgement is of special importance when 1 or 2 of these findings are present.
Although vital signs are an essential part of physical assessment, their deviation from normal may not reliably indicate infection. 3 Fever in the hospitalized patient commonly prompts blood culture, but this variable alone predicts bacteremia in only 2.4-10.2% of cases. 3,7 Although fever in medical patients most commonly arises from microbial infection, it may also occur with drug reaction, malignancy, thromboembolism, and ischemia. 8 Fever is particularly nonspecific in the early postoperative period. 9,10
Leukocytosis is generally considered a sign of microbial infection but has been an inconsistent predictor of bacteremia. Several studies have correlated leukocytosis with bacteremia, 4,7,11 while others have not. 3,5,10,12,13 In 1 study, band count ≥ 1500 mm3 and ESR ≥ 30 mm/h predicted focal bacterial infection but not bacteremia. 3 Others have reported that age over 50, elevated temperature, rigors, intravenous drug abuse, acute abdomen, diabetes mellitus, major comorbidity, hypotension, tachycardia, band count ≥ 1500 mm3 or >20%, elevated alkaline phosphatase, low serum albumin, bacteriuria, immunosuppression, ICU hospitalization, and lack of antibiotics are independent predictors for bacteremia, 3,7,11,14,15,16 although none of these factors was uniformly predictive in each study. Anemia, hyponatremia, and presence of a central venous catheter have been associated with S. aureus bacteremia. 17
Additional laboratory variables recently correlated with bacteremia include plasma procalcitonin, neutrophilic elastase-α1-antitrypsin, and lactoferrin, 4 as well as tumor necrosis factor-α, interleukin-6, phospholipase A2, and complement product C3A. 18,19,20 C-reactive protein has a variable correlation with bacteremia. 18,20,21
Our data must be viewed from the standpoint of several limitations. First, all data were derived from patients in whom blood culture was actually performed and in whom at least a single episode of bloodstream infection was documented. As such, selection bias could make our findings less applicable to patients at low risk for bacteremia. Second, although our study population was heterogeneous, we excluded patients with marked leukopenia (WBC count < 3000) or leukocytosis (WBC count > 45,000) from our analysis and thus may have missed patients with high illness acuity. Although at least 1 study has reported that a low WBC count does not portend a higher rate of bacteremia, 20 others have shown that neutropenia carries a greater risk for infection, particularly fungal or polymicrobial infection. 22 It is certainly reasonable to have a lower clinical threshold to obtain blood cultures in these patients.
Third, our study analyzed patients having positive blood cultures without regard to primary illness, comorbidities, or hospital service. Such variables may have value in predicting bacteremia. 23,24 On the other hand, using only objective data may lend broader clinical applicability to our findings. Although not studied here, other variables that might have predictive value for bacteremia include culture time until positivity, presence and nature of antibiotic therapy, and result of recent prior blood culture.
In summary, our findings show that optimal utilization of blood culture may be furthered by attention to a concurrent CBC. Our stratification based simply on WBC count and differential may allow discrimination between patients with low-risk and high-risk of bacteremia. In low-risk patients, it may be cost-effective to hold a specimen until CBC results are available and to proceed with culture only if predictive findings are present. Conversely, patients identified as high risk (ie, those with WBC count ≥ 12,000 with significant bandemia and neutrophilia) may benefit from timely institution of empiric antibiotic prior to availability of full microbiologic data.
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