Exposure to Non-Antimicrobial Drugs and Risk of Infection with Antibiotic-Resistant Enterobacteriaceae.

Antimicrobial resistance (AMR) has consistently been linked to antibiotic use. However, the roles of commonly prescribed non-antimicrobial drugs as drivers of AMR may be under-appreciated. Here, we studied a cohort of patients with community-acquired pyelonephritis and assessed the association of exposure to non-antimicrobial drugs at the time of hospital admission with infection with drug-resistant organisms (DRO). Associations identified on bivariate analyses were tested using a treatment effects estimator that models both outcome and treatment probability. Exposure to proton-pump inhibitors, beta-blockers, and antimetabolites was significantly associated with multiple resistance phenotypes. Clopidogrel, selective serotonin reuptake inhibitors, and anti-Xa agents were associated with single-drug resistance phenotypes. Antibiotic exposure and indwelling urinary catheters were covariates associated with AMR. Exposure to non-antimicrobial drugs significantly increased the probability of AMR in patients with no other risk factors for resistance. Non-antimicrobial drugs may affect the risk of infection with DRO through multiple mechanisms. If corroborated using additional datasets, these findings offer novel directions for predicting and mitigating AMR.

The potential benefit of a second C-reactive protein measurement in patients with gram-negative bacteraemia presenting to the emergency medicine department.

BACKGROUND: Low C-reactive protein in acute bacterial infections could convey the erroneous impression of a mild infection. We focussed on gram-negative bacteraemia, a phenomenon frequently seen at the emergency room. METHODS: Of 2200 patients with gram-negative bacteraemia, 460 patients with first C-reactive protein <30 mg/L and 460 patients with C-reactive protein >187 mg/L were reviewed. Following exclusions, we finally investigated 229 and 289 patients with low and high C-reactive protein concentrations, respectively. RESULTS: The cohort was divided into low and high C-reactive protein groups. Median first C-reactive protein was 13.6 and 219.9 mg/L, respectively (interquartile range 6.4-21.6 and 195-270.1). Compared to patients with first high C-reactive protein, patients with first low C-reactive protein concentrations had a significant five-fold higher C-reactive protein level with their second test. CONCLUSIONS: Patients with gram-negative bacteraemia can present with C-reactive protein within the range of apparently healthy individuals. A second C-reactive protein might help to avoid an erroneous decision regarding the severity of the infection.

Using the kinetics of C-reactive protein response to improve the differential diagnosis between acute bacterial and viral infections.

PURPOSE: Differential diagnosis between acute viral and bacterial infection is an emerging common challenge for a physician in the emergency department. Serum C-reactive protein (CRP) is used to support diagnosis of bacterial infection, but in patients admitted with low CRP, its ability to discriminate between viral and bacterial infections is limited. We aimed to use two consecutive CRP measurements in order to improve differential diagnosis between bacterial and viral infection. METHODS: A single-center retrospective cohort (n = 1629) study of adult patients admitted to the emergency department with a subsequent microbiological confirmation of either viral or bacterial infection. Trend of CRP was defined as the absolute difference between the first two measurements of CRP divided by the time between them, and we investigated the ability of this parameter to differentiate between viral and bacterial infection. RESULTS: In patients with relatively low initial CRP concentration (< 60 mg/L, n = 634 patients), where the uncertainty regarding the type of infection is the highest, the trend improved diagnosis accuracy (AUC 0.83 compared to 0.57 for the first CRP measurement). Trend values above 3.47 mg/L/h discriminated bacterial from viral infection with 93.8% specificity and 50% sensitivity. CONCLUSIONS: The proposed approach for using the kinetics of CRP in patients whose first CRP measurement is low can assist in differential diagnosis between acute bacterial and viral infection.

Anemia measurements to distinguish between viral and bacterial infections in the emergency department.

The clinical diagnosis of acute infections in the emergency department is a challenging task due to the similarity in symptom presentation between virally and bacterially infected individuals, while the use of routine laboratory tests for pathogen identification is often time-consuming and may contain contaminants. We investigated the ability of various anemia-related parameters, including hemoglobin, red cell distribution width (RDW), and iron, to differentiate between viral and bacterial infection in a retrospective study of 3883 patients admitted to the emergency department with a confirmed viral (n = 1238) or bacterial (n = 2645) infection based on either laboratory tests or microbiological cultures. The ratio between hemoglobin to RDW was found to be significant in distinguishing between virally and bacterially infected patients and outperformed other anemia measurements. Moreover, the predictive value of the ratio was high even in patients presenting with low C-reactive protein values (< 21 mg/L). We followed the dynamics of hemoglobin, RDW, and the ratio between them up to 72 h post emergency department admission, and observed a consistent discrepancy between virally and bacterially infected patients over time. Additional analysis demonstrated higher levels of ferritin and lower levels of iron in bacterially infected compared with virally infected patients. The anemia measurements were associated with length of hospital stay, where all higher levels, except for RDW, corresponded to a shorter hospitalization period. We highlighted the importance of various anemia measurements as an additional host-biomarker to discern virally from bacterially infected patients.

The implementation of rapid microbial identification via MALDI-ToF reduces mortality in gram-negative but not gram-positive bacteremia.

Our goals were to study the effect of rapid microbial identification (RMI) of positive blood culture on patient's outcome and to identify specific microbiological characteristics related to clinical benefit of RMI. This was a retrospective-cohort study of hospitalized, adult patients with bacteremia. The outcome of patients with bacteremia episodes was compared before vs. after the initiation of RMI. RMI was done by matrix-assisted laser desorption/ionization time-of-flight testing of microcolonies. The study included 1460 and 2710 cases in the pre- and post-intervention periods, respectively. There were similar rates of gram-negative, gram-positive, anaerobes, and polymicrobial infections, but higher rate of contaminants in the intervention period (39.9 vs. 43.7%, p = 0.019). The median time-to-identification decreased from 47.5 to 21.3 h (p < 0.001). Post-intervention, the median LOS declined from 10.83 to 9.79 days (p = 0.016), the rate of ICU transfer declined from 13.8 to 11.6% (p = 0.054), and the mortality rate declined from 20.9 to 18.3% (p = 0.047). The improvement in outcome variables remained statistically significant in multivariate analysis when performed for all episodes and non-contaminants but not for contaminants. The mortality declined in gram-negative bacteremia (20% vs. 15.5%, p = 0.005 in multivariate analysis) but not in gram-positive bacteremia (18.1% vs. 18.5%). RMI reduces mortality from gram-negative but not gram-positive bacteremia.

Septic patients presenting with apparently normal C-reactive protein: A point of caution for the ER physician.

The presentation of septic patients with low C-reactive protein (CRP) concentrations to the emergency room (ER) might convey an erroneous impression regarding the severity of the disease.We analyzed a retrospective study of septic patients admitted to the internal medicine departments of a relatively large tertiary medical center, following admission to the ER. These patients had CRP concentrations of <31.9 mg/L, the determined cut-off for CRP concentrations in a large cohort of apparently healthy individuals in the community (n = 17,214, upper limit of mean + 3 standard deviations).By processing the electronic medical records, we found 2724 patients with a diagnosis of sepsis, 476 of whom had an admission CRP concentration of <31.9 mg/L. Following further analysis of these records, we found that 34 of the 175 patients (19.4%) who fulfilled the definition of sepsis, died within 1 week of hospitalization. Of special interest was the finding that within <24 h, a significant increment from a median CRP of 16.1 mg/L (IQR 7.9-22.5) to 58.6 mg/L (IQR 24.2-134.4), (P < .001) was noted, accompanied by a velocity change from 0.4 ±â€Š0.29 to 8.3 ±â€Š24.2 mg/L/h following antibiotic administration (P < .001).ER physicians should take into consideration that septic patients with a high in-hospital mortality rate can present with CRP concentrations that are within the range observed in apparently healthy individuals in the community. A second CRP test obtained within 24 h following antibiotic administration might influence attitudes regarding the severity of the disease.