Masashi Yamanouchi, MD

Fever is a nonspecific phenomenon that can result from many inciting causes such as infection, inflammation, malignancy, thromboembolic disease, drugs, and endocrine disease. In hospitalized patients, one of the most important clinical considerations is bacteremia. Although vital signs compose 3 of the 4 current criteria for the diagnosis of Systemic Inflammatory Response Syndrome (SIRS),1, 2 they contribute little to the diagnosis of the cause, which can be inflammation or infection. Unfortunately, the physician's clinical diagnosis of bacteremia lacks both sensitivity and specificity.35 Blood culture acquisition is a simple and basic diagnostic procedure routinely used in clinical practice that yields essential information for the evaluation of various infectious diseases.6 Positive blood cultures can demonstrate not only an infectious cause of disease but also the microbiological response to antibiotic therapy.7 However, studies have reported that 35% to 50% of positive blood cultures are falsely positive owing to contamination.711 False‐positive cultures may lead to the use of inappropriate or unnecessary antibiotics, additional testing and consultation, and prolonged hospitalizations that increase patient care costs.9, 12

Nursing staff caring for patients are generally able to assess oral intake, general clinical state, and care requirements. Moreover, the nursing staff are often able to identify problems with patients before physicians.13 In Japan, nurse‐assessed food consumption of every meal is standardized, and is frequently regarded as an indicator of the patient's clinical status, akin to a vital sign. In this context, we hypothesized that quantitative variations in food consumption could accurately distinguish those patients with or without bacteremia.

MATERIALS AND METHODS

RESULTS

During the study period, 851 patients aged 16 to 99 years (66.8 16.6), were eligible for inclusion (Figure 1). Baseline characteristics of the subjects are given in Table 1. The mean body temperature ( standard deviation [SD]) was 38.1 1.1C, and the mean CRP level was 8.7 8.1 mg/dL. The results show that the patients had at least 2 SIRS criteria with elevations in temperature and heart rate. Of the 851 patients entered into the study, only 122 (14.3%) had positive blood cultures. Of these, 75 patients (8.8%) were considered to have true‐positive blood culture. In this study, blood cultures were taken at the time of onset of fever, whether that was a new inpatient admission, or during the course of an admission to the hospital. On average, blood cultures were drawn 12 days after admission (SD, 5.6 days). Despite the variation in onset of fever, the inverse relationship of blood culture positivity to decreased food consumption held true (data not shown). Gram‐positive and Gram‐negative organisms were obtained in near equal amounts. The main pathogens recovered from the true‐positive blood cultures were Gram‐positive cocci (26 patients [34.7% in true‐positive blood cultures]), and Gram‐negative bacilli (46 patients [61.3%]), as shown in Table 1. The underlying clinical diagnosis included 28 urinary tract infections; 9 catheter‐associated infections; 5 cases each of pneumonia and abscess; 3 cases of phlebitis; 2 cases of meningitis and osteomyelitis; 1 case each of infective endocarditis, decubitus ulcer, and pelvic infection; and 17 cases of infection with an unknown focus.

Figure 1

Low, moderate, and high food consumption groups consisted of 344 patients (40.4%), 152 patients (17.9%), and 354 patients (41.7%), respectively (Table 1). Of these, 63 patients, 6 patients, and 6 patients had bacteremia in the low, moderate, and high food consumption group, respectively. In order to distinguish those patients who had decreased food consumption compared to almost normal food consumption, low and moderate food consumption groups were combined and compared to the high food consumption group. Comparison of the combined low and moderate food consumption group versus the high food consumption group revealed a sensitivity of 92.0% and a negative predictive value of 98.3% for excluding true bacteremia. Conversely, the specificity (45.1%) and the positive predictive value (13.9%) were poor.

In the univariate analysis, the following variables were not statistically significantly associated with true bacteremia: age, heart rate, and leukocyte counts. Significant univariate predictors of bacteremia and their associated cut‐off points were body temperature of 36 or 38C (odds ratio [OR], 2.5; 95% CI, 1.54.4), CRP 10.0 mg/dL (OR, 2.0; 95% CI, 1.23.2), and food consumption (OR, 8.5; 95% CI, 3.818.6) (Table 2). There was no evidence of colinearity. In the final stepwise logistic regression (Table 3), the significant predictors of bacteremia were body temperature of 36 or 38C (OR, 2.4; 95% CI, 1.44.2; P = 0.002), C‐reactive protein of 10.0 mg/dL (OR, 1.9; 95% CI, 1.23.0; P = 0.011), and food consumption (OR, 7.5; 95% CI, 3.416.6; P < 0.001). We identified only 6 patients with bacteremia in the high food consumption group. Three of the patients had been previously treated with antibiotics for conditions including infective endocarditis, osteomyelitis, and myelodysplasic syndrome.

On further analysis, we excluded patients who had received antibiotics before blood culture acquisition. There were 661 patients in this subanalysis. Low, moderate, and high food consumption groups consisted of 282 patients (41.4%), 118 patients (17.3%), and 261 patients (38.3%), respectively. Of these, 50 patients (17.7%), 5 patients (4.2%), and 4 patients (1.5%) had bacteremia in the low, moderate, and high food consumption groups, respectively. The sensitivity and negative predictive values were 93.2% and 98.5%, respectively. In the stepwise logistic regression, significant predictors of bacteremia were body temperature of 36 or 38C (OR, 3.0; 95% CI, 1.55.6; P = 0.001), CRP 10.0 mg/dL (OR, 2.1; 95% CI, 1.23.7; P = 0.006), and food consumption (OR, 9.3; 95% CI, 3.326.1; P < 0.001).

DISCUSSION

We found that in a group of 851 Japanese patients who were suspected with bacterial infection, the estimated food consumption was negatively associated, both significantly and independently, with the subsequent isolation of microorganisms from their blood cultures. If validated in other studies, this simple rule of thumb can provide the clinician with reasonable confidence that a febrile patient has a low probability of being bacteremic, as long as the appetite remains normal. Both the sensitivity and the negative predictive value were extremely high at 92.3% and 98.3%, respectively, suggesting that adequate oral intake is a strong marker against the presence of bacteremia. In this study, it was the strongest predictor of bacteremia in multivariate analysis. After including only antibiotic‐naive patients, the sensitivity and the negative predictive values were 93.2% and 98.5%, respectively. Administration of antibiotics may lead to improved appetite in febrile patients despite bacteremia in the presence of fever, and therefore, inquiring about recent or current antimicrobial usage should be a requirement when considering oral intake as an indicator of bacteremia.

Our study has limitations. Since we did not make treatment decisions based on oral intake, we cannot conclude that it is safe to withhold antibiotic treatment on the basis of food intake alone. Additionally, this study would need to be repeated across many different age groups and racial groups to ensure applicability to the general population. It is also unknown whether this rule would be applicable to patients with underlying immunosuppression. Finally, although inter‐rater reliability was high in our center, nurses in other settings may not be as diligent in their assessment of food consumption. The high inter‐assessor reliability in our setting, however, suggests that objective assessment of food intake can be performed reliably in settings in which accurate documentation of food consumption is expected.

In summary, we found that normal food intake was strongly and negatively associated with bacteremia in febrile patients. This observation, if validated in other settings, may serve as a simple aid to assist in the clinical diagnosis of bacteremia or for recruitment of patients with a high likelihood of bacteremia into clinical trials.

Fever is a nonspecific phenomenon that can result from many inciting causes such as infection, inflammation, malignancy, thromboembolic disease, drugs, and endocrine disease. In hospitalized patients, one of the most important clinical considerations is bacteremia. Although vital signs compose 3 of the 4 current criteria for the diagnosis of Systemic Inflammatory Response Syndrome (SIRS),1, 2 they contribute little to the diagnosis of the cause, which can be inflammation or infection. Unfortunately, the physician's clinical diagnosis of bacteremia lacks both sensitivity and specificity.35 Blood culture acquisition is a simple and basic diagnostic procedure routinely used in clinical practice that yields essential information for the evaluation of various infectious diseases.6 Positive blood cultures can demonstrate not only an infectious cause of disease but also the microbiological response to antibiotic therapy.7 However, studies have reported that 35% to 50% of positive blood cultures are falsely positive owing to contamination.711 False‐positive cultures may lead to the use of inappropriate or unnecessary antibiotics, additional testing and consultation, and prolonged hospitalizations that increase patient care costs.9, 12

Nursing staff caring for patients are generally able to assess oral intake, general clinical state, and care requirements. Moreover, the nursing staff are often able to identify problems with patients before physicians.13 In Japan, nurse‐assessed food consumption of every meal is standardized, and is frequently regarded as an indicator of the patient's clinical status, akin to a vital sign. In this context, we hypothesized that quantitative variations in food consumption could accurately distinguish those patients with or without bacteremia.

MATERIALS AND METHODS

RESULTS

During the study period, 851 patients aged 16 to 99 years (66.8 16.6), were eligible for inclusion (Figure 1). Baseline characteristics of the subjects are given in Table 1. The mean body temperature ( standard deviation [SD]) was 38.1 1.1C, and the mean CRP level was 8.7 8.1 mg/dL. The results show that the patients had at least 2 SIRS criteria with elevations in temperature and heart rate. Of the 851 patients entered into the study, only 122 (14.3%) had positive blood cultures. Of these, 75 patients (8.8%) were considered to have true‐positive blood culture. In this study, blood cultures were taken at the time of onset of fever, whether that was a new inpatient admission, or during the course of an admission to the hospital. On average, blood cultures were drawn 12 days after admission (SD, 5.6 days). Despite the variation in onset of fever, the inverse relationship of blood culture positivity to decreased food consumption held true (data not shown). Gram‐positive and Gram‐negative organisms were obtained in near equal amounts. The main pathogens recovered from the true‐positive blood cultures were Gram‐positive cocci (26 patients [34.7% in true‐positive blood cultures]), and Gram‐negative bacilli (46 patients [61.3%]), as shown in Table 1. The underlying clinical diagnosis included 28 urinary tract infections; 9 catheter‐associated infections; 5 cases each of pneumonia and abscess; 3 cases of phlebitis; 2 cases of meningitis and osteomyelitis; 1 case each of infective endocarditis, decubitus ulcer, and pelvic infection; and 17 cases of infection with an unknown focus.

Figure 1

Low, moderate, and high food consumption groups consisted of 344 patients (40.4%), 152 patients (17.9%), and 354 patients (41.7%), respectively (Table 1). Of these, 63 patients, 6 patients, and 6 patients had bacteremia in the low, moderate, and high food consumption group, respectively. In order to distinguish those patients who had decreased food consumption compared to almost normal food consumption, low and moderate food consumption groups were combined and compared to the high food consumption group. Comparison of the combined low and moderate food consumption group versus the high food consumption group revealed a sensitivity of 92.0% and a negative predictive value of 98.3% for excluding true bacteremia. Conversely, the specificity (45.1%) and the positive predictive value (13.9%) were poor.

In the univariate analysis, the following variables were not statistically significantly associated with true bacteremia: age, heart rate, and leukocyte counts. Significant univariate predictors of bacteremia and their associated cut‐off points were body temperature of 36 or 38C (odds ratio [OR], 2.5; 95% CI, 1.54.4), CRP 10.0 mg/dL (OR, 2.0; 95% CI, 1.23.2), and food consumption (OR, 8.5; 95% CI, 3.818.6) (Table 2). There was no evidence of colinearity. In the final stepwise logistic regression (Table 3), the significant predictors of bacteremia were body temperature of 36 or 38C (OR, 2.4; 95% CI, 1.44.2; P = 0.002), C‐reactive protein of 10.0 mg/dL (OR, 1.9; 95% CI, 1.23.0; P = 0.011), and food consumption (OR, 7.5; 95% CI, 3.416.6; P < 0.001). We identified only 6 patients with bacteremia in the high food consumption group. Three of the patients had been previously treated with antibiotics for conditions including infective endocarditis, osteomyelitis, and myelodysplasic syndrome.

On further analysis, we excluded patients who had received antibiotics before blood culture acquisition. There were 661 patients in this subanalysis. Low, moderate, and high food consumption groups consisted of 282 patients (41.4%), 118 patients (17.3%), and 261 patients (38.3%), respectively. Of these, 50 patients (17.7%), 5 patients (4.2%), and 4 patients (1.5%) had bacteremia in the low, moderate, and high food consumption groups, respectively. The sensitivity and negative predictive values were 93.2% and 98.5%, respectively. In the stepwise logistic regression, significant predictors of bacteremia were body temperature of 36 or 38C (OR, 3.0; 95% CI, 1.55.6; P = 0.001), CRP 10.0 mg/dL (OR, 2.1; 95% CI, 1.23.7; P = 0.006), and food consumption (OR, 9.3; 95% CI, 3.326.1; P < 0.001).

DISCUSSION

We found that in a group of 851 Japanese patients who were suspected with bacterial infection, the estimated food consumption was negatively associated, both significantly and independently, with the subsequent isolation of microorganisms from their blood cultures. If validated in other studies, this simple rule of thumb can provide the clinician with reasonable confidence that a febrile patient has a low probability of being bacteremic, as long as the appetite remains normal. Both the sensitivity and the negative predictive value were extremely high at 92.3% and 98.3%, respectively, suggesting that adequate oral intake is a strong marker against the presence of bacteremia. In this study, it was the strongest predictor of bacteremia in multivariate analysis. After including only antibiotic‐naive patients, the sensitivity and the negative predictive values were 93.2% and 98.5%, respectively. Administration of antibiotics may lead to improved appetite in febrile patients despite bacteremia in the presence of fever, and therefore, inquiring about recent or current antimicrobial usage should be a requirement when considering oral intake as an indicator of bacteremia.

Our study has limitations. Since we did not make treatment decisions based on oral intake, we cannot conclude that it is safe to withhold antibiotic treatment on the basis of food intake alone. Additionally, this study would need to be repeated across many different age groups and racial groups to ensure applicability to the general population. It is also unknown whether this rule would be applicable to patients with underlying immunosuppression. Finally, although inter‐rater reliability was high in our center, nurses in other settings may not be as diligent in their assessment of food consumption. The high inter‐assessor reliability in our setting, however, suggests that objective assessment of food intake can be performed reliably in settings in which accurate documentation of food consumption is expected.

In summary, we found that normal food intake was strongly and negatively associated with bacteremia in febrile patients. This observation, if validated in other settings, may serve as a simple aid to assist in the clinical diagnosis of bacteremia or for recruitment of patients with a high likelihood of bacteremia into clinical trials.

Fever is a nonspecific phenomenon that can result from many inciting causes such as infection, inflammation, malignancy, thromboembolic disease, drugs, and endocrine disease. In hospitalized patients, one of the most important clinical considerations is bacteremia. Although vital signs compose 3 of the 4 current criteria for the diagnosis of Systemic Inflammatory Response Syndrome (SIRS),1, 2 they contribute little to the diagnosis of the cause, which can be inflammation or infection. Unfortunately, the physician's clinical diagnosis of bacteremia lacks both sensitivity and specificity.35 Blood culture acquisition is a simple and basic diagnostic procedure routinely used in clinical practice that yields essential information for the evaluation of various infectious diseases.6 Positive blood cultures can demonstrate not only an infectious cause of disease but also the microbiological response to antibiotic therapy.7 However, studies have reported that 35% to 50% of positive blood cultures are falsely positive owing to contamination.711 False‐positive cultures may lead to the use of inappropriate or unnecessary antibiotics, additional testing and consultation, and prolonged hospitalizations that increase patient care costs.9, 12

Nursing staff caring for patients are generally able to assess oral intake, general clinical state, and care requirements. Moreover, the nursing staff are often able to identify problems with patients before physicians.13 In Japan, nurse‐assessed food consumption of every meal is standardized, and is frequently regarded as an indicator of the patient's clinical status, akin to a vital sign. In this context, we hypothesized that quantitative variations in food consumption could accurately distinguish those patients with or without bacteremia.

MATERIALS AND METHODS

RESULTS

During the study period, 851 patients aged 16 to 99 years (66.8 16.6), were eligible for inclusion (Figure 1). Baseline characteristics of the subjects are given in Table 1. The mean body temperature ( standard deviation [SD]) was 38.1 1.1C, and the mean CRP level was 8.7 8.1 mg/dL. The results show that the patients had at least 2 SIRS criteria with elevations in temperature and heart rate. Of the 851 patients entered into the study, only 122 (14.3%) had positive blood cultures. Of these, 75 patients (8.8%) were considered to have true‐positive blood culture. In this study, blood cultures were taken at the time of onset of fever, whether that was a new inpatient admission, or during the course of an admission to the hospital. On average, blood cultures were drawn 12 days after admission (SD, 5.6 days). Despite the variation in onset of fever, the inverse relationship of blood culture positivity to decreased food consumption held true (data not shown). Gram‐positive and Gram‐negative organisms were obtained in near equal amounts. The main pathogens recovered from the true‐positive blood cultures were Gram‐positive cocci (26 patients [34.7% in true‐positive blood cultures]), and Gram‐negative bacilli (46 patients [61.3%]), as shown in Table 1. The underlying clinical diagnosis included 28 urinary tract infections; 9 catheter‐associated infections; 5 cases each of pneumonia and abscess; 3 cases of phlebitis; 2 cases of meningitis and osteomyelitis; 1 case each of infective endocarditis, decubitus ulcer, and pelvic infection; and 17 cases of infection with an unknown focus.

Figure 1

Low, moderate, and high food consumption groups consisted of 344 patients (40.4%), 152 patients (17.9%), and 354 patients (41.7%), respectively (Table 1). Of these, 63 patients, 6 patients, and 6 patients had bacteremia in the low, moderate, and high food consumption group, respectively. In order to distinguish those patients who had decreased food consumption compared to almost normal food consumption, low and moderate food consumption groups were combined and compared to the high food consumption group. Comparison of the combined low and moderate food consumption group versus the high food consumption group revealed a sensitivity of 92.0% and a negative predictive value of 98.3% for excluding true bacteremia. Conversely, the specificity (45.1%) and the positive predictive value (13.9%) were poor.

In the univariate analysis, the following variables were not statistically significantly associated with true bacteremia: age, heart rate, and leukocyte counts. Significant univariate predictors of bacteremia and their associated cut‐off points were body temperature of 36 or 38C (odds ratio [OR], 2.5; 95% CI, 1.54.4), CRP 10.0 mg/dL (OR, 2.0; 95% CI, 1.23.2), and food consumption (OR, 8.5; 95% CI, 3.818.6) (Table 2). There was no evidence of colinearity. In the final stepwise logistic regression (Table 3), the significant predictors of bacteremia were body temperature of 36 or 38C (OR, 2.4; 95% CI, 1.44.2; P = 0.002), C‐reactive protein of 10.0 mg/dL (OR, 1.9; 95% CI, 1.23.0; P = 0.011), and food consumption (OR, 7.5; 95% CI, 3.416.6; P < 0.001). We identified only 6 patients with bacteremia in the high food consumption group. Three of the patients had been previously treated with antibiotics for conditions including infective endocarditis, osteomyelitis, and myelodysplasic syndrome.

On further analysis, we excluded patients who had received antibiotics before blood culture acquisition. There were 661 patients in this subanalysis. Low, moderate, and high food consumption groups consisted of 282 patients (41.4%), 118 patients (17.3%), and 261 patients (38.3%), respectively. Of these, 50 patients (17.7%), 5 patients (4.2%), and 4 patients (1.5%) had bacteremia in the low, moderate, and high food consumption groups, respectively. The sensitivity and negative predictive values were 93.2% and 98.5%, respectively. In the stepwise logistic regression, significant predictors of bacteremia were body temperature of 36 or 38C (OR, 3.0; 95% CI, 1.55.6; P = 0.001), CRP 10.0 mg/dL (OR, 2.1; 95% CI, 1.23.7; P = 0.006), and food consumption (OR, 9.3; 95% CI, 3.326.1; P < 0.001).

DISCUSSION

We found that in a group of 851 Japanese patients who were suspected with bacterial infection, the estimated food consumption was negatively associated, both significantly and independently, with the subsequent isolation of microorganisms from their blood cultures. If validated in other studies, this simple rule of thumb can provide the clinician with reasonable confidence that a febrile patient has a low probability of being bacteremic, as long as the appetite remains normal. Both the sensitivity and the negative predictive value were extremely high at 92.3% and 98.3%, respectively, suggesting that adequate oral intake is a strong marker against the presence of bacteremia. In this study, it was the strongest predictor of bacteremia in multivariate analysis. After including only antibiotic‐naive patients, the sensitivity and the negative predictive values were 93.2% and 98.5%, respectively. Administration of antibiotics may lead to improved appetite in febrile patients despite bacteremia in the presence of fever, and therefore, inquiring about recent or current antimicrobial usage should be a requirement when considering oral intake as an indicator of bacteremia.

Our study has limitations. Since we did not make treatment decisions based on oral intake, we cannot conclude that it is safe to withhold antibiotic treatment on the basis of food intake alone. Additionally, this study would need to be repeated across many different age groups and racial groups to ensure applicability to the general population. It is also unknown whether this rule would be applicable to patients with underlying immunosuppression. Finally, although inter‐rater reliability was high in our center, nurses in other settings may not be as diligent in their assessment of food consumption. The high inter‐assessor reliability in our setting, however, suggests that objective assessment of food intake can be performed reliably in settings in which accurate documentation of food consumption is expected.

In summary, we found that normal food intake was strongly and negatively associated with bacteremia in febrile patients. This observation, if validated in other settings, may serve as a simple aid to assist in the clinical diagnosis of bacteremia or for recruitment of patients with a high likelihood of bacteremia into clinical trials.