A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia.

BACKGROUND: Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP. METHODS: In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days. Treatment was 14 days in patients with concurrent gram-positive bacteremia. The primary efficacy end points were day 28 all-cause mortality (ACM; noninferiority margin, 10%) and investigator-assessed clinical response at test of cure (TOC; noninferiority margin, 12.5%) in the intention-to-treat population. RESULTS: Overall, 726 patients were randomized (tedizolid, n = 366; linezolid, n = 360). Baseline characteristics, including incidence of methicillin-resistant Staphylococcus aureus (31.3% overall), were well balanced. Tedizolid was noninferior to linezolid for day 28 ACM rate: 28.1% and 26.4%, respectively (difference, -1.8%; 95% confidence interval [CI]: -8.2 to 4.7). Noninferiority of tedizolid was not demonstrated for investigator-assessed clinical cure at TOC (tedizolid, 56.3% vs linezolid, 63.9%; difference, -7.6%; 97.5% CI: -15.7 to 0.5). In post hoc analyses, no single factor accounted for the difference in clinical response between treatment groups. Drug-related adverse events occurred in 8.1% and 11.9% of patients who received tedizolid and linezolid, respectively. CONCLUSIONS: Tedizolid was noninferior to linezolid for day 28 ACM in the treatment of gram-positive ventilated HABP/VABP. Noninferiority of tedizolid for investigator-assessed clinical response at TOC was not demonstrated. Both drugs were well tolerated. CLINICAL TRIALS REGISTRATION: NCT02019420.

A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study).

BACKGROUND: Imipenem combined with the ß-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). METHODS: This was a randomized, controlled, double-blind phase 3 trial. Adults with HABP/VABP were randomized 1:1 to imipenem/cilastatin/relebactam 500 mg/500 mg/250 mg or piperacillin/tazobactam 4 g/500 mg, intravenously every 6 hours for 7-14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (patients who received study therapy, excluding those with only gram-positive cocci at baseline). The key secondary endpoint was clinical response 7-14 days after completing therapy in the MITT population. RESULTS: Of 537 randomized patients (from 113 hospitals in 27 countries), the MITT population comprised 264 imipenem/cilastatin/relebactam and 267 piperacillin/tazobactam patients; 48.6% had ventilated HABP/VABP, 47.5% APACHE II score ≥15, 24.7% moderate/severe renal impairment, 42.9% were ≥65 years old, and 66.1% were in the intensive care unit. The most common baseline pathogens were Klebsiella pneumoniae (25.6%) and Pseudomonas aeruginosa (18.9%). Imipenem/cilastatin/relebactam was noninferior (P < .001) to piperacillin/tazobactam for both endpoints: day 28 all-cause mortality was 15.9% with imipenem/cilastatin/relebactam and 21.3% with piperacillin/tazobactam (difference, -5.3% [95% confidence interval {CI}, -11.9% to 1.2%]), and favorable clinical response at early follow-up was 61.0% and 55.8%, respectively (difference, 5.0% [95% CI, -3.2% to 13.2%]). Serious adverse events (AEs) occurred in 26.7% of imipenem/cilastatin/relebactam and 32.0% of piperacillin/tazobactam patients; AEs leading to treatment discontinuation in 5.6% and 8.2%, respectively; and drug-related AEs (none fatal) in 11.7% and 9.7%, respectively. CONCLUSIONS: Imipenem/cilastatin/relebactam is an appropriate treatment option for gram-negative HABP/VABP, including in critically ill, high-risk patients. CLINICAL TRIALS REGISTRATION: NCT02493764.

Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19. Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC. Primary outcome was time-to-recovery by day 28. Key secondary endpoints included 28-day mortality. Results: Between October 16, 2020 and December 31, 2021, a total of 1019 participants received study treatment (509 abatacept; 510 shared placebo), constituting the modified intention-to-treat cohort. Participants had a mean age 54.8 (SD 14.6) years, 60.5% were male, 44.2% Hispanic/Latino and 13.7% Black. No statistically significant difference for the primary endpoint of time-to-recovery was found with a recovery-rate-ratio of 1.14 (95% CI 1.00-1.29; p=0.057) compared with placebo. We observed a substantial improvement in 28-day all-cause mortality with abatacept versus placebo (11.0% vs. 15.1%; odds ratio [OR] 0.62 [95% CI 0.41- 0.94]), leading to 38% lower odds of dying. Improvement in mortality occurred for participants requiring oxygen/noninvasive ventilation at randomization. Subgroup analysis identified the strongest effect in those with baseline C-reactive protein >75mg/L. We found no statistically significant differences in adverse events, with safety composite index slightly favoring abatacept. Rates of secondary infections were similar (16.1% for abatacept; 14.3% for placebo). Conclusions: Addition of single-dose intravenous abatacept to standard-of-care demonstrated no statistically significant change in time-to-recovery, but improved 28-day mortality. Trial registration: ClinicalTrials.gov ( NCT04593940 ).

Arterial hypertension treatment in octogenarians with dementia according to ESC/ESH-2018: Three-year follow-up. / Tratamiento de la hipertensión arterial en octogenarios con demencia según ESC/ESH-2018: seguimiento a 3 años.

OBJECTIVE: To determine the control of systolic blood pressure (SBP) retrospectively according to the recommendations of the ESC/ESH-2018 guideline and its relationship with mortality in octogenarian patients with dementia. PATIENTS AND METHODS: Preliminary, longitudinal, observational, retrospective study, including 65 patients ≥80 years with diagnosis of dementia and arterial hypertension admitted to a psychogeriatric unit during 2015. The main variables were SBP control according to the recommendations of the ESC/ESH-2018 guideline, considering desirable SBP (130-139mmHg), undesirable SBP (suboptimal <130mmHg and elevated SBP ≥140mmHg) and mortality at 3 years in patients with antihypertensive treatment at discharge (n = 53). RESULTS: Mean age, 86.7±4.31 years (63% women); severe functional dependence (Barthel index <40): 67.7%; severe cognitive impairment (GDS-Riesberg ≥6): 86.3%; high comorbidity: 49%; mortality at 3 years: 41 (63.1%). Patients with arterial hypertension and cardiovascular comorbidity had a higher prescription of antihypertensive drugs (2.07 vs. 1.18, p=.002). Three years mortality was lower in patients with desirable SBP (44.4%) versus undesirable SBP (72.7%) groups, although it was not statistically significant. CONCLUSIONS: The percentage of patients in treatment with suboptimal SBP was elevated especially in hypertensive patients without cardiovascular comorbidity. We found a trend for higher mortality in undesirable SBP groups compared to desirable SBP.

Preclampsia severa y síndrome de Hellp / Severe pre-eclampsia and Hellp's syndrome

Respectivamente revisamos 15 casos de preclampsia severa con síndrome HELLP. Las pacientes presentaron hipertensión arterial severa, los síntomas principales fueron dolor en epigastrio e hipocondrio derecho que se presentó en 66.6 por ciento de las pacientes, náuseas y vómitos en 53.8 por ciento y edema de miembros inferiores en 60 por ciento. La principal edad de afección fue en la tercera década de la vida, y el tercer trimestre del embarazo en el que se presentaron todos los cuadros, la complicación principal fue insuficiencia renal aguda en 80 por ciento de las pacientes, tres pacientes fallecieron 20 por ciento, las causas fueron SIRPA, hemorragia cerebral y choque hipovolémico

Síndrome Hellp hematoma subcapsular e infarto hepáticos, presentación de dos casos clínicos / Hellp's syndrome Hepatic subcapsular hematoma and hepatic infarction. presentation of two clinical cases

Se presentan dos casos de síndrome de hellp complicados con hematoma subcapsular e infarto hepáticos. La presentación de ambas pacientes fue con tendencia a la hipotensión posterior a la interrupción quirúrgica del embarazo, con grandes requerimientos de sangre y hemoderivados leucocitosis importante, insuficiencia renal e insuficiencia hepática severa que ocasionó que ambas pacientes desarrollan encefalopatía hepatíca grado III-IV, una paciente falleció con falla multisistémica y la otra paciente sobrevivió pero con signos de daño hepático residual

Síndrome antifosfolípidos, embarazo molar e infarto cerebral. Presentación de un caso / Antiphospholipids Syndrome molar pregnancy and cerebral infarction

Se describe el caso clínico de una paciente de 14 años de edad, la cual presentó un embarazo molar, hipertención e infarto cerebral isquémico en región temporoparietal izquierda. Se determinaron anticuerpos anticoagulantes lúpicos, resultados positivos, correspondiendo el cuadro clínico a un síndrome de anticuerpos antifosfolípidos, el cual clínicamente se asocia a trastornos oclusivos arteriales o venosos en diversas regiones del organismo, así como también a trombosis venosas profundas en extremidades, cerebro y pulmón, además de relacionarse con pérdidas recurrentes de embarazos tempranos, preeclampsia severa de aparición temprana de retardo en el crecimiento intrauterino

Preeclampsia severa síndrome HELLP e Insuficiencia renal / Severe preeclampsia, Hellp's syndrome and renal failure

Se presenta un estudio retrospectivo realizado en la unidad de cuidados intensivos del nuevo Hospital Civil de Guadalajara con paciente que desarrolló preeclampsia severa y síndrome HELLP, 70 pacientes de las cuales 30 desarrollaron insuficiencia renal aguda, de éstas 25 fueron catalogadas como necrosis tubular aguda y cinco con necrosis cortical bilateral. Todas las pacientes (30) con insuficiencia renal aguda presentaron hipertensión arterial severa, además de depleción de volumen plasmático circulante con un promedio de PVC de 6 cm de agua (en 20 pacientes), los promedios de urea de 64.2 mg/dl y creatinina 4.2 mg/dl. Seis pacientes del grupo fallecieron, tres por hemorragia cerebral, dos choque hipovolémico y una paciente por falla multisistémica. La causa del desarrollo de insuficiencia renal aguda se debe a disminución del volumen circulante, endoteliosis glomerular y vasoconstricción severa