Procalcitonin-guided Antibiotic Treatment in Patients With Positive Blood Cultures: A Patient-level Meta-analysis of Randomized Trials.

BACKGROUND: Whether procalcitonin (PCT)-guided antibiotic management in patients with positive blood cultures is safe remains understudied. We performed a patient-level meta-analysis to investigate effects of PCT-guided antibiotic management in patients with bacteremia. METHODS: We extracted and analyzed individual data of 523 patients with positive blood cultures included in 13 trials, in which patients were randomly assigned to receive antibiotics based on PCT levels (PCT group) or a control group. The main efficacy endpoint was duration of antibiotic treatment. The main safety endpoint was mortality within 30 days. RESULTS: Mean duration of antibiotic therapy was significantly shorter for 253 patients who received PCT-guided treatment than for 270 control patients (-2.86 days [95% confidence interval [CI], -4.88 to -.84]; P = .006). Mortality was similar in both arms (16.6% vs 20.0%; P = .263). In subgroup analyses by type of pathogen, we noted a trend of shorter mean antibiotic durations in the PCT arm for patients infected with gram-positive organisms or Escherichia coli and significantly shorter treatment for subjects with pneumococcal bacteremia. In analysis by site of infection, antibiotic exposure was shortened in PCT subjects with Streptococcus pneumoniae respiratory infection and those with E. coli urogenital infections. CONCLUSIONS: This meta-analysis of patients with bacteremia receiving PCT-guided antibiotic management demonstrates lower antibiotic exposure without an apparent increase in mortality. Few differences were demonstrated in subgroup analysis stratified by type or site of infection but notable for decreased exposure in patients with pneumococcal pneumonia and E. coli urogenital infections.

Procalcitonin to guide antibiotic decision making.

PURPOSE OF REVIEW: There is convincing evidence linking antibiotic-stewardship efforts which include the infection marker procalcitonin (PCT) to more rational use of antibiotics with improvements in side-effects and clinical outcomes. This is particularly true in the setting of respiratory infection and sepsis. Yet, some recent trials have shown no benefit of PCT-guided care. Our aim was to discuss the benefits and limitations of using PCT for early infection recognition, severity assessment and therapeutic decisions in individual patients based on most the recent study data. RECENT FINDINGS: Current evidence from randomized trials, and meta-analyses of these trials, indicates that PCT-guided antibiotic stewardship results in a reduction in antibiotic use and antibiotic side-effects, which translates into improved survival of patients with respiratory infections and sepsis. Notably, initial PCT levels have been found to be helpful in defining the risk for bacterial infection in the context of a low pretest probability for bacterial infections (i.e., patients with bronchitis or chronic bastructive pulmonary disease exacerbation). Monitoring of repeated PCT measurements over time has also been found helpful for estimating recovery from bacterial infection and prognosis in higher risk situations (i.e., pneumonia or sepsis) and results in early and safe discontinuation of antibiotic therapy. Some trials, however, did not find a strong effect of PCT guidance which may be explained by low protocol adherence, assessment using only a single rather than repeat PCT levels and lower antibiotic exposure in control group patients. Using PCT in the right patient population, with high-sensitivity assays and with adequate training of physicians is important to increase protocol adherence and reduce antibiotic exposure. SUMMARY: Inclusion of PCT into antibiotic stewardship algorithms has the potential to improve the diagnostic and therapeutic management of patients presenting with respiratory illnesses and sepsis, and holds great promise to mitigate the global bacterial resistance crisis and move from a default position of standardized care to more personalized treatment decisions.

A high C-reactive protein/procalcitonin ratio predicts Mycoplasma pneumoniae infection.

Background Discriminating Mycoplasma pneumoniae (MP) from Streptococcus pneumoniae (SP) and viral etiologies of community-acquired pneumonia (CAP) is challenging but has important implications regarding empiric antibiotic therapy. We investigated patient parameters upon hospital admission to predict MP infection. Methods All patients hospitalized in a tertiary care hospital between 2013 and 2017 for CAP with a confirmed etiology were analyzed using logistic regression analyses and area under the receiver operator characteristics (ROC) curves (AUC) for associations between demographic, clinical and laboratory features and the causative pathogen. Results We analyzed 568 patients with CAP, including 47 (8%) with MP; 152 (27%) with SP and 369 (65%) with influenza or other viruses. Comparing MP and SP by multivariate logistic regression analysis, younger age (odds ration [OR] 0.56 per 10 years, 95% CI 0.42-0.73), a lower neutrophil/lymphocyte ratio (OR 0.9, 0.82-0.99) and an elevated C-reactive protein/procalcitonin (CRP/PCT) ratio (OR 15.04 [5.23-43.26] for a 400 mg/µg cut-off) independently predicted MP. With a ROC curve AUC of 0.91 (0.80 for the >400 mg/µg cutoff), the CRP/PCT ratio was the strongest predictor of MP vs. SP. The discriminatory value resulted from significantly lower PCT values (p < 0.001) for MP, while CRP was high in both groups (p = 0.057). Comparing MP and viral infections showed similar results with again the CRP/PCT ratio providing the best information (AUC 0.83; OR 5.55 for the >400 mg/µg cutoff, 2.26-13.64). Conclusions In patients hospitalized with CAP, a high admission CRP/PCT ratio predicts M. pneumoniae infection and may improve empiric management.

Relationship of Nutritional Status, Inflammation, and Serum Albumin Levels During Acute Illness: A Prospective Study.

BACKGROUND: Low serum albumin levels resulting from inflammation-induced capillary leakage or disease-related anorexia during acute illness are associated with poor outcomes. We investigated the relationship of nutritional status and inflammation with low serum albumin levels and 30-day mortality in a large cohort. METHODS: We prospectively enrolled adult patients in the medical emergency department of a Swiss tertiary care center and investigated associations of C-reactive protein (CRP) and Nutritional Risk Screening 2002 as markers of inflammation and poor nutritional status, respectively, with low serum albumin levels and mortality using multivariate regression analyses. RESULTS: Among the 2465 patients, 1019 (41%) had low serum albumin levels (<34 g/L), 619 (25.1%) had increased nutritional risk (Nutritional Risk Screening 2002 ≥3), and 1086 (44.1%) had CRP values >20 mg/L. Multivariate analyses adjusted for age, gender, diagnosis, and comorbidities revealed elevated CRP values (adjusted odds ratio [OR] 10.51, 95% confidence interval, 7.51-14.72, P <.001) and increased malnutrition risk (adjusted OR 2.87, 95% confidence interval, 1.98-4.15, P <.001) to be associated with low serum albumin levels, even adjusting for both parameters. Low serum albumin levels, elevated CRP values, and increased nutritional risk independently predicted 30-day mortality, with areas under the curve of 0.77, 0.70, and 0.75, respectively. Combination of these 3 parameters showed an area under the curve of 0.82 to predict mortality. CONCLUSIONS: Elevated parameters of inflammation and high nutritional risk were independently associated with hypoalbuminemia. All 3 parameters independently predicted mortality. Combining them during initial evaluation of patients in emergency departments facilitates mortality risk stratification.

Validation of a Prediction Rule for Legionella Pneumonia in Emergency Department Patients.

We validated a clinical prediction rule for Legionella based on clinical parameters (dry cough, fever) and laboratory findings (C-reactive protein, lactate dehydrogenase, sodium, platelet counts) in 713 consecutive patients with community-acquired pneumonia. The Legionella Score performed well in estimating the likelihood for Legionella infection and thus may help to direct diagnostic and therapeutic decisions.

Validation of the hospital frailty risk score in a tertiary care hospital in Switzerland: results of a prospective, observational study.

OBJECTIVES: Recently, the Hospital Frailty Risk Score based on a derivation and validation study in the UK has been proposed as a low-cost, systematic screening tool to identify older, frail patients who are at a greater risk of adverse outcomes and for whom a frailty-attuned approach might be useful. We aimed to validate this Score in an independent cohort in Switzerland. DESIGN: Secondary analysis of a prospective, observational study (TRIAGE study). SETTING: One 600-bed tertiary care hospital in Aarau, Switzerland. PARTICIPANTS: Consecutive medical inpatients aged ≥75 years that presented to the emergency department or were electively admitted between October 2015 and April 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was all-cause 30-day mortality. Secondary endpoints were length of hospital stay, hospital readmission, functional impairment and quality of life measures. We used multivariate regression analyses. RESULTS: Of 4957 included patients, 3150 (63.5%) were classified as low risk, 1663 (33.5%) intermediate risk, and 144 (2.9%) high risk for frailty. Compared with the low-risk group, patients in the moderate risk and high-risk groups had increased risk for 30-day mortality (OR (OR) 2.53, 95% CI 2.09 to 3.06, p<0.001 and OR 4.40, 95% CI 2.94 to 6.57, p<0.001) with overall moderate discrimination (area under the ROC curve 0.66). The results remained robust after adjustment for important confounders. Similarly, we found longer length of hospital stay, more severe functional impairment and a lower quality of life in higher risk group patients. CONCLUSION: Our data confirm the prognostic value of the Hospital Frailty Risk Score to identify older, frail people at risk for mortality and adverse outcomes in an independent patient population. TRIAL REGISTRATION NUMBER: NCT01768494; Post-results.

Gain of length-loss of strength? Alteration in muscle strength after femoral leg lengthening in young patients: a prospective longitudinal observational study.

This study aimed to determine the alteration in maximum isokinetic torque in patients after intramedullary femoral leg lengthening. Thirty patients with a median leg-length discrepancy of 3.0 cm underwent femoral limb lengthening with an intramedullary motorized device. Maximum isokinetic, concentric torque of the extensors, and flexors of the knee was measured before (n=30) and 2 years after surgery (n=21). Postoperatively, a significant difference remained for the maximum isokinetic torque of the extensors (22%) between the lengthened and the normal leg, which might have been caused by muscle response to the distraction procedure itself in the form of higher stiffness, less immediate displacement, and inconsistent force relaxation properties. However, we provide evidence that physiotherapy after limb lengthening should focus on extensors to prevent loss of strength.