Case report: mRNA-1273 COVID-19 vaccine-associated myopericarditis: Successful treatment and re-exposure with colchicine.

Introduction: Vaccine-induced myocarditis is a rare complication of messenger RNA (mRNA) COVID-19 vaccines. Case presentation: We report a case of acute myopericarditis in a recipient of allogeneic hematopoietic cells following the first dose of the mRNA-1273 vaccine and the successful administration of a second and third dose while on prophylactic treatment with colchicine to successfully complete the vaccination. Conclusion: Treatment and prevention of mRNA-vaccine-induced myopericarditis represent a clinical challenge. The use of colchicine is feasible and safe to potentially reduce the risk of this rare but severe complication and allows re-exposure to an mRNA vaccine.

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

BACKGROUND: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. OBJECTIVE AND DESIGN: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. SUBJECTS AND METHODS: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. RESULTS: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). CONCLUSIONS: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.

Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment: a patient-level meta-analysis from randomized controlled trials.

Objectives: Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission. Methods: We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15-89 [CKD 2-4] and GFR<15 [CKD 5]). The main efficacy and safety endpoints were duration of antibiotic treatment and 30-day mortality. Results: Mean duration of antibiotic treatment was significantly shorter in PCT-guided (n=2,492) compared to control patients (n=2,510) (9.5-7.6 days; adjusted difference in days -2.01 [95% CI, -2.45 to -1.58]). CKD 5 patients had overall longer treatment durations, but a 2.5-day reduction in treatment duration was still found in patients receiving in PCT-guided care (11.3 vs. 8.6 days [95% CI -3.59 to -1.40]). There were 397 deaths in 2,492 PCT-group patients (15.9%) compared to 460 deaths in 2,510 control patients (18.3%) (adjusted odds ratio, 0.88 [95% CI 0.78 to 0.98)]. Effects of PCT-guidance on antibiotic treatment duration and mortality were similar in subgroups stratified by infection type and clinical setting (p interaction >0.05). Conclusions: This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates.

Role of procalcitonin use in the management of sepsis.

Important aspects of sepsis management include early diagnosis as well as timely and specific treatment in the first few hours of triage. However, diagnosis and differentiation from non-infectious causes often cause uncertainties and potential time delays. Correct use of antibiotics still represents a major challenge, leading to increased risk for opportunistic infections, resistances to multiple antimicrobial agents and toxic side effects, which in turn increase mortality and healthcare costs. Optimized procedures for reliable diagnosis and management of antibiotic therapy has great potential to improve patient care. Herein, biomarkers have been shown to improve infection diagnosis, help in early risk stratification and provide prognostic information which helps optimizing therapeutic decisions ("antibiotic stewardship"). In this context, the use of the blood infection marker procalcitonin (PCT) has gained much attention. There is still no gold standard for the detection of sepsis and use of conventional diagnostic approaches are restricted by some limitations. Therefore, additional tests are necessary to enable early and reliable diagnosis. PCT has good discriminatory properties to differentiate between bacterial and viral inflammations with rapidly available results. Further, PCT adds to risk stratification and prognostication, which may influence appropriate use of health-care resources and therapeutic options. PCT kinetics over time also improves the monitoring of critically ill patients with sepsis and thus influences decisions regarding de-escalation of antibiotics. Most importantly, PCT helps in guiding antibiotic use in patients with respiratory infection and sepsis by limiting initiation and by shortening treatment duration. To date, PCT is the best studied biomarker regarding antibiotic stewardship. Still, further research is needed to understand optimal use of PCT, also in combination with other remerging diagnostic tests for most efficient sepsis care.

Biomarkers of Infection: Are They Useful in the ICU?

Biomarkers are increasingly used in patients with serious infections in the critical care setting to complement clinical judgment and interpretation of other diagnostic and prognostic tests. The main purposes of such blood markers are (1) to improve infection diagnosis (i.e., differentiation between bacterial vs. viral vs. fungal vs. noninfectious), (2) to help in the early risk stratification and thus provide prognostic information regarding the risk for mortality and other adverse outcomes, and (3) to optimize antibiotic tailoring to individual needs of patients ("antibiotic stewardship").Especially in critically ill patients, in whom sepsis is a major cause of morbidity and mortality, rapid diagnosis is desirable to start timely and specific treatment.Besides some biomarkers, such as procalcitonin, which is well established and has shown positive effects in regard to utilization of antimicrobials and clinical outcomes, there is a growing number of novel markers from different pathophysiological pathways, where the final proof of an added value to clinical judgment and ultimately clinical benefit to patients is still lacking.Without a doubt, the addition of blood biomarkers to clinical medicine has had a strong impact on the way we care for patients today. Recent trials show that as an adjunct to other clinical and laboratory parameters these markers provide important information about risks for bacterial infection and resolution of infection. Moreover, biomarkers can help to optimize management of patients with serious illness in the intensive care unit, thereby offering more individualized treatment courses with overall improvements in clinical outcomes.