De-escalation antibiotic therapy alleviates organ injury through modulation of NETs formation during sepsis

Empiric broad-spectrum antimicrobials therapy is suggested to be started immediately for sepsis patients. Empiric antimicrobial therapy should be narrowed once pathogen identification and sensitivities are established. However, the detailed mechanisms of de-escalation strategy are still unclear. Here we hypothesized neutrophil extracellular traps (NETs) played an essential role and de-escalation strategy might alleviate organs injury through regulation of NETs formation in sepsis. We evaluated the effect of imipenem and ceftriaxone on NETs formation in vitro and examined the role of reactive oxygen species (ROS). Next, we designed de-escalation and escalation strategy in cecum ligation and puncture (CLP) models. Organ injury, inflammatory cytokines, NETs levels were compared and evaluated. In CLP models, de-escalation therapy resulted in an increased serum MPO-DNA level during the early stage and decreased MPO-DNA level during late stage, which exerted the reverse effects in escalation therapy. Inflammatory response and organ injury exacerbated when eliminated NETs with DNAse I during the early stage of sepsis (p < 0.01). Histopathological analysis showed decreased injury in lung, liver, and intestine in de-escalation therapy compared with escalation therapy (p < 0.01). De-escalation therapy results in the highest 6-day survival rate compared with the control group (p < 0.01), however, no significant difference was found between de-escalation and escalation group (p = 0.051). The in vitro study showed that the imipenem could promote, while the ceftriaxone could inhibit the formation of NETs in PMA-activated PMNs through a ROS-dependent manner. We firstly demonstrate that de-escalation, not escalation, therapy reduces organ injury, decreases inflammatory response by promoting NETs formation in the early stage, and inhibiting NETs formation in the late stage of sepsis.

The budgetary impact of alemtuzumab in multiple sclerosis in Quito, Ecuador. Payer’s perspective

Introduction: Multiple sclerosis is a neurological condition that causes disabilities and is most common in young adults. It imposes high financial costs affecting the quality of life of patients, families, and society. It is critical to measure the budgetary impact of new technologies to treat this disease. Objective: The aim of the article is to estimate the budgetary impact of introducing alemtuzumab as an escalation therapy in patients diagnosed with Recurrent Remitting Multiple Sclerosis and treated in Quito, Ecuador. Materials and methods: A cohort of 85 patients receiving treatment with disease-modifying therapies was used, within a 5-year timeframe, between 2021 and 2025. The baseline scenario, including the percentages of administration of the different drugs, is compared with the alternative scenario, including alemtuzumab. The cost assessment included only direct medical resources. To obtain local resources for management of the disease, a neurologist and clinical expert who treats most of the patients in Quito was consulted. Results: Considering a cohort of 85 patients with active Recurrent Remitting Multiple Sclerosis, the average global budget impact in 5 years would be USD 10,603,230.00 in the base case and USD 9,995,817.00 in the alemtuzumab scenario. Conclusion: The inclusion of alemtuzumab as escalation therapy represents budgetary savings over the next 5 years (2021-2025).

The opportunities of third-generation cephalosporin usage in outpatient surgery

The adherence to the principles of rational antibacterial therapy is of great significance, namely the prescription of a medication to achieve the quickest possible clinical and bacteriologic convalescence, the spectrum of mechanisms of a drug should affect possible germ, overcome the possible mechanisms of resistance and make the highest concentration in infectious focus. Moreover, the prescribed drug should be convenient for outpatient usage. The important principle of infection treatment is a de-escalation therapy that provides clinical and economic benefits both for a patient and health facility. The usage of the antibiotic cefdinir is effective and safe in hospital and outpatient treatment.

Integrating Osteopathic Evaluation and Treatment in a Case of Opioid-Induced Hyperalgesia

This paper reviews a multimodal approach to the treatment of acute pain. Early recognition of systemic changes in pain indicators may be efficacious for the patient and practitioner to understand the subjective pain response. The application of osteopathic manipulative medicine may be beneficial during de-escalation therapy of opioid pain medication when the patient is experiencing symptoms consistent with opioid-induced hyperalgesia syndrome. Improved education and recognition of opioid-induced hyperalgesia can potentially improve medical management with the use of osteopathic manipulative treatment.

High-Flow Nasal Cannula for COVID-19 Patients: A Multicenter Retrospective Study in China

Background: High-flow nasal cannula (HFNC) may help avoid intubation of hypoxemic patients suffering from COVID-19; however, it may also contribute to delaying intubation, which may increase mortality. Here, we aimed to identify the predictors of HFNC failure among patients with COVID-19.Methods: We performed a multicenter retrospective study in China from January 15 to March 31, 2020. Two centers in Wuhan (resource-limited centers) enrolled 32 patients, and four centers outside Wuhan enrolled 34 cases. HFNC failure was defined as the requirement of escalation therapy (NIV or intubation). The ROX index (the ratio of SpO2/FiO2 to the respiratory rate) was calculated.Results: Among the 66 patients, 29 (44%) cases experienced HFNC failure. The ROX index was much lower in failing patients than in successful ones after 1, 2, 4, 8, 12, and 24 h of HFNC. The ROX index was independently associated with HFNC failure (OR = 0.65; 95% CI: 0.45–0.94) among the variables collected before and 1 h after HFNC. To predict HFNC failure tested by ROX index, the AUC was between 0.73 and 0.79 for the time points of measurement 1–24 h after HFNC initiation. The HFNC failure rate was not different between patients in and outside Wuhan (41% vs. 47%, p = 0.63). However, the time from HFNC initiation to intubation was longer in Wuhan than that outside Wuhan (median 63 vs. 22 h, p = 0.02). Four patients in Wuhan underwent intubation due to cardiac arrest; in contrast, none of the patients outside Wuhan received intubation (13 vs. 0%, p = 0.05). The mortality was higher in Wuhan than that out of Wuhan, but the difference did not reach statistical significance (31 vs. 12%, p = 0.07).Conclusion: The ROX index can be used to predict HFNC failure among COVID-19 patients to avoid delayed intubation, which may occur in the resource-limited area.

De-escalation Antibiotic Therapy Alleviates Organ Injury through Modulation of NET Formation during Sepsis

Empiric broad-spectrum antimicrobials therapy is suggested to be started immediately for sepsis patients. Empiric antimicrobial therapy should be narrowed once pathogen identification and sensitivities are established. However, the detail mechanisms of de-escalation strategy are still unclear. Here we hypothesized neutrophil extracellular trap (NETs) played an essential role and de-escalation strategy might alleviate organs injury through regulation of NETs formation in sepsis. We evaluated the effect of imipenem and ceftriaxone on NETs formation in vitro and examined the role of reactive oxygen species (ROS). Next, we designed de-escalation and escalation strategy based on their effects on NETs formation in CLP model. Organ injury, inflammatory cytokines, NETs levels were compared and evaluated. The in vitro study showed that imipenem and ceftriaxone had opposite effects on NETs formation in activated neutrophils. De-escalation therapy resulted in an evaluated MPO-DNA during early stage and decreased MPO-DNA during late stage, which exerted the reverse effects in escalation therapy sepsis animal model. Inflammatory response and organ injury exacerbated when eliminated NETs with DNAseI during early stage of sepsis (p<0.01). Histopathological analysis showed decreased injury in lung, liver and intestine in de-escalation therapy compared with escalation therapy (p<0.01). De-escalation therapy results in the highest 6-day survival rate compared with the control group (p<0.01), however, no significant difference was found between de-escalation and escalation group (p=0.051). We demonstrate that de-escalation, not escalation, therapy reduces organ injury, decreases inflammatory response by promoting NETs formation in the early stage and inhibiting NETs formation in the late stage of sepsis.

Successful de-escalation antibiotic therapy using cephamycins for sepsis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia: A sequential 25-case series

Carbapenems are frequently used to treat infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E), but carbapenem-resistant Enterobacteriaceae bacteria are a clinical concern. Although cephamycins (cefmetazole; CMZ) have been shown to be effective against mild cases of ESBL-E infection, data on their use for severe ESBL-E infections with sepsis or septic shock remain scarce. Herein, we discuss a de-escalation therapy to CMZ that could be used after empiric antibiotic therapy in ICU patients with sepsis or septic shock caused by ESBL-E bacteremia. A sequence of 25 cases diagnosed with sepsis or septic shock caused by ESBL-E bacteria was evaluated. The attending infectious disease specialist physicians selected the antibiotics and decided the de-escalation timing. The median SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) severity scores were 8 and 30; the rate of septic shock was 60%. Infections originated most frequently with urinary tract infection (UTI) (56%) and Escherichia coli (85%). Eleven patients were de-escalated to CMZ after vital signs were stable, and all survived. No patients died of UTI regardless of with or without de-escalation. The median timing of de-escalation antibiotic therapy after admission was 4 days (range, 3–6 days). At the time of de-escalation, the median SOFA score fell from 8 to 5, the median APACHE II score from 28 to 22, and the rate of septic shock from 55% to 0%. We conclude that for sepsis in UTI caused by ESBL-E bacteremia, de-escalation therapy from broad-spectrum antibiotics to CMZ is a potential treatment option when vital signs are stable.

Cladribina para el tratamiento de la esclerosis múltiple remitente recurrente: nueva alternativa para Latinoamérica

Cladribine is a modified deoxyadenosine that evades the action of the enzyme adenosine deaminase, which results in an immunosuppressive effect through lymphopenia, leading to an immune cells reconstitution that helps in the treatment of autoimmune diseases such as relapsing–remitting multiple sclerosis (RRMS). Since we currently have a wide range of medications to treat RRMS, it is of great interest to identify the role that cladribine plays among all options. The main objective of this narrative review is to provide useful information, with the aid of a clinical case study, which helps physicians in making decisions to treat patients with RRMS, and provide them with the best options for efficacy and safety. Due to its selective immunosuppressive effects, cladribine is indicated for the treatment of moderate to severe activity RRMS, either in escalation therapy or as induction therapy. In this article we will also analyze the characteristics of this drug to establish the scientific bases that guide the therapeutic decision making, taking into account the balance of risks and benefits for the patient.