Managing hospitalized patients with bacterial infections: the price-to-pay upon site of infection.

INTRODUCTION: Infections impose a significant burden on healthcare costs worldwide. We aimed to explore antibiotic- and hospital-related costs of infections needing admission in a tertiary university hospital in Greece. METHODS: We performed a prospective cohort study in the medical care unit of a tertiary university hospital in Greece, for the period May 2016 to May 2018. Patients admitted with respiratory, urinary, gastrointestinal tract, skin, soft tissue and bone infections or primary bacteremia were included in this study. Costs of hospitalization and unit cost of antibiotic regimen were retrieved from a database for Greek hospitals containing data for each International Classification of Diseases (ICD-10) code and the national formulary respectively, and manually calculated for each patient. RESULTS: Antibiotic costs represent approximately 14-40% of total hospital-related costs depending on infection studied. Skin, soft tissue and bone infections and primary bacteremia led hospital- and antibiotic-related costs, with median costs of €6370 (interquartile range (IQR) 3330.90-11 503.90), €2519.90 (IQR 431.50-8371.10), €4418.10 (IQR 2335-8281.90) and €1394.30 (IQR 519.12-6459.90), respectively. Antibiotic- and hospital-related costs significantly differs with site of infection (p<0.0001). Length of stay is strongly correlated with antibiotic- and hospital-related costs, while site of infection is moderately related to antibiotic cost (eta value 0.445), and hospital-related cost (eta value 0.387). CONCLUSION: Healthcare-related costs vary substantially depending on site of infection. Information about real-life costs can drive best decisions and help to reduce healthcare expenditures.

Patterns, price and predictors of successful empiric antibiotic therapy in a real-world setting.

WHAT IS KNOWN AND OBJECTIVE: Prompt and appropriate empiric antibiotic therapy (EAT) remains the cornerstone of successful outcomes, while the majority of blood cultures do not identify pathogen. We aimed to report patterns of EAT and its impact on outcomes and associated medical costs, while exploring predictors of its success in a real-world setting. METHODS: We retrospectively utilized the prospective registry of the medical unit of a tertiary university hospital, including patients admitted with diagnosis of infection between 1st May 2016 and 1st May 2018. Costs of hospitalization and unit of antibiotic regimen were retrieved from a database regarding Greek hospitals containing hospitalization-cost data for each ICD-10 code and the national formulary, respectively. RESULTS: A total of 489 patients were included in this study. Mean age was 61.3 years, 53% were males, while intra-abdominal infections predominated (55%). The most commonly administered EAT included quinolones (48%), followed by piperacillin/tazobactam (18%), or other regimens alone or in combination. EAT was successful in 67% and failed in 33% of cases. Fourteen patients died of the infection before EAT was switched, while among 55 patients that EAT had to be modified, mortality was 22%. Presence of urinary tract infection and use of quinolones, least predicted for failure of EAT [OR:0.15 (0.07-0.35), p < 0.0001, OR:0.53 (0.32-0.90), p = 0.019, respectively], in contrast to presence of sepsis [OR:3.11 (1.79-5.40), p < 0.0001]. Patients with failure had longer length of stay [7(5-11) versus 4 (3-6) days], higher antibiotic [201.9 (97.8-471.8) vs 104.6 (60.2-187.7) euros] and hospitalization costs [1409.3 (945.4-2311.6) vs 759.4 (516.5-1036.5) euros] (p < 0.0001). DISCUSSION: We observed significantly increased antibiotic-related, healthcare-related costs and length of stay in patients with failure of EAT. Moreover, in our cohort, absence of sepsis, presence of urinary tract infection and use of quinolones better predicted for success of EAT. WHAT IS NEW AND CONCLUSIONS: Appropriate selection of EAT is crucial to ensure better outcomes and minimize costs.

An MRI study of immune checkpoint inhibitor-induced musculoskeletal manifestations myofasciitis is the prominent imaging finding.

OBJECTIVE: To assess: (i) the prevalence, and clinical and imaging characteristics of immune checkpoint inhibitor (ICI)-induced musculoskeletal immune-related adverse events (ir-AEs) in a prospective manner and (ii) whether serum levels of cytokines associated with the Th1/Th2/Th17 response are differentially expressed in patients with and without musculoskeletal Ir-AEs. METHODS: All patients treated with ICI who developed musculoskeletal manifestations were referred to the Rheumatology Department, and an MRI of the involved area(s) was performed. RESULTS: During the study period, a total of 130 patients were treated with ICIs. Of these, 10 (7.7%) developed ICI-induced Ir-AEs. The median time from ICI treatment since development of symptoms was 2.5 months. Three different patterns of musculoskeletal manifestations were found: (i) prominent joint involvement (n = 3); (ii) prominent 'periarticular' involvement (n = 4). These patients had diffuse swelling of the hands, feet or knees. MRI depicted mild synovitis with more prominent myositis and/or fasciitis in the surrounding tissues in all cases; (iii) myofasciitis (n = 3). Clinically, these patients presented with pain in the knee(s)/thigh(s), whereas MRI depicted myofasciitis of the surrounding muscles. Patients with musculoskeletal ir-AEs had significantly higher oncologic response rates compared with patients not exhibiting musculoskeletal ir-AEs (50% vs 12.5%, respectively, P = 0.0016). Cytokine levels associated with a Th1/Th2/Th17 response were similar between patients with and without musculoskeletal ir-AEs. Overall, symptoms were mild/moderate and responded well to treatment, with no need for ICI discontinuation. CONCLUSION: In our cohort, ICI-induced musculoskeletal manifestations developed in 7.7% of patients. Imaging evidence of myofasciitis was found in most patients, indicating that the muscle/fascia is more frequently involved than the synovium.

How well does qSOFA correspond to underlying systemic inflammatory response?

Need for prompt recognition and management of sepsis recently led to the introduction of qSOFA score. However, its association with underlying host inflammatory response remains unclear, while previous studies have challenged its performance in non - intensive care unit (ICU) patients comparing to previously used systemic inflammatory response syndrome (SIRS) criteria. Between June 2016 and April 2017, we performed a prospective observational study in the medical ward of a tertiary hospital to explore the relation of qSOFA ≥ 2 and <2 to underlying inflammatory response, as this is mirrored in levels of serum pro- and anti-inflammatory mediators i.e. IL-6, IL-10 and TNF-α. A total of 100 consecutive patients were finally included in this study. Comparable levels [(pg/ml) median (IQR)] of IL-6 [200 (53-200) vs 65.1 (17.3-200)], IL-10 [ 7 (2.3-170.6) vs 2.3 (2.3-27.7)], and TNF-α [4 (4-46.1) vs 46.06 (4-227.2)] were noted between group of patients with qSOFA ≥ 2 or <2. Nevertheless, prognosis was worse in patients with qSOFA ≥ 2 showing longer length of stay [10 (7-25) vs 5 (3-7) days, p = .03] and lower recovery rates (41 vs 93%, p < .0001). Our results underline the need for prompt management of critically ill patients in presence of systemic inflammatory response regardless of qSOFA score, partly reflecting its low sensitivity comparing to previously used SIRS criteria.

Sepsis favors high-on-clopidogrel platelet reactivity.

High-on-treatment platelet reactivity (HPR) is associated with ischemic events in patients on antiplatelet therapy with a history of cardiovascular disease. On the other hand, recent data have associated sepsis with adverse cardiovascular events in patients admitted with bacteremia or respiratory infection. We aimed to assess P2Y12-mediated platelet reactivity (PR) during sepsis and recovery in patients under clopidogrel. This was a prospective observational study. Incoming patients presenting with signs/symptoms of sepsis already on a maintenance dose of clopidogrel of 75 mg qd for cardiovascular events were included in this study. Patients were assessed for their PR on presentation and following septic syndrome, using the VerifyNow point-of-care P2Y12 assay. Patients were excluded in the presence of evidence of noncompliance to antiplatelet regimen or in need of discontinuation during this study. Twenty-two septic patients on clopidogrel were included in this study (Supplemental Figure S1). Clopidogrel was administered for previous stroke, coronary, and peripheral artery disease in 27.3, 40.9, and 31.8% of patients, respectively. The main site of infection was respiratory tract followed by urinary tract, while the same amounts of gram-negative and -positive pathogens were isolated. HPR was noted in 77% and 29% of patients during sepsis and recovery, respectively, presenting a significant decrease in P2Y12 reaction units values during follow-up [240.7 ± 58.3 versus 179.5 ± 58.4, 95% CI (-102.7, -39.76), p = 0.0002]. Five patients died of infection, while no adverse cardiovascular events were noted in our study. Our study shows that sepsis may favor HPR, which is reversed when recovery occurs. This finding may underlie the adverse cardiovascular events in patients admitted with sepsis, possibly requiring alteration of antiplatelet regimen during the inflammation period.

Platelet reactivity in sepsis syndrome: results from the PRESS study.

Platelet activation mediates systemic inflammatory response during infection. However, data on platelet reactivity (PR) varies among different settings. We assessed PR along different stages of sepsis and tried to predict for determinants of its variance. In parallel, we evaluated it as an early bedside diagnostic biomarker. This was an observational prospective cohort study. Incoming patients were assorted to distinct groups of uncomplicated infection, sepsis, and severe sepsis/septic shock. A control group of healthy volunteers was used as comparison. PR was assessed using the bedside point-of-care VerifyNow assay, in P2Y12 reaction units (PRU) alongside with levels of major inflammatory markers and whole blood parameters. A total of 101 patients and 27 healthy volunteers were enrolled. PR significantly and reversibly increases during sepsis compared to uncomplicated infection and healthy controls (244 ± 66.7 vs 187.33 ± 60.98, p < 0.001 and 192.17 ± 47.51, p < 0.001, respectively). In severe sepsis, PR did not significantly differ compared to other groups. Sepsis stage uniquely accounts for 15.5% of PR in a linear regression prediction model accounting for 30% of the variance of PR (F = 8.836, p < 0.001). PRU >253 had specificity of 91.2% and sensitivity of 40.8% in discriminating septic from non-septic patients. The addition of PRU to SOFA and qSOFA scores significantly increased their c-statistic (AUC SOFA + PRU, 0.867 vs SOFA, 0.824, p < 0.003 and AUC qSOFA + PRU, 0.842 vs qSOFA, 0.739, p < 0.001), making them comparable (AUC SOFA + PRU vs qSOFA + PRU, p = 0.4). PR significantly and reversibly increases early in sepsis, but seems to exhaust while disease progresses. Bedside assessment of PR can provide robust discriminative accuracy in the early diagnosis of septic patients.