RESUMEN
BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. METHODS: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. RESULTS: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. CONCLUSION: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.
Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Ritonavir/uso terapéutico , Anciano , COVID-19 , Enfermedad Crítica , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , Nivel de Atención , Resultado del TratamientoAsunto(s)
Angina de Pecho/etiología , Bloqueo de Rama/diagnóstico , Oclusión Coronaria/diagnóstico , Oído Externo , Anciano , Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Cardioversión Eléctrica , Electrocardiografía , Paro Cardíaco/etiología , Paro Cardíaco/terapia , Humanos , MasculinoRESUMEN
BACKGROUND: Whether sepsis-associated diaphragm dysfunction may improve despite the exposure of mechanical ventilation in critically ill patients is unclear. This study aims at describing the diaphragm function time course of septic and non-septic mechanically ventilated patients. METHODS: Secondary analysis of two prospective observational studies of mechanically ventilated patients in whom diaphragm function was assessed twice: within the 24 h after intubation and when patients were switched to pressure support mode, by measuring the endotracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). Change in diaphragm function was expressed as the difference between Ptr,stim measured under pressure support mode and Ptr,stim measured within the 24 h after intubation. Sepsis was defined according to the Sepsis-3 international guidelines upon inclusion. In a sub-group of patients, the right hemidiaphragm thickness was measured by ultrasound. RESULTS: Ninety-two patients were enrolled in the study. Sepsis upon intubation was present in 51 (55%) patients. In septic patients, primary reason for ventilation was acute respiratory failure related to pneumonia (37/51; 73%). In non-septic patients, main reasons for ventilation were acute respiratory failure not related to pneumonia (16/41; 39%), coma (13/41; 32%) and cardiac arrest (6/41; 15%). Ptr,stim within 24 h after intubation was lower in septic patients as compared to non-septic patients: 6.3 (4.9-8.7) cmH2O vs. 9.8 (7.0-14.2) cmH2O (p = 0.004), respectively. The median (interquartile) duration of mechanical ventilation between first and second diaphragm evaluation was 4 (2-6) days in septic patients and 3 (2-4) days in non-septic patients (p = 0.073). Between first and second measurements, the change in Ptr,stim was + 19% (- 13-61) in septic patients and - 7% (- 40-12) in non-septic patients (p = 0.005). In the sub-group of patients with ultrasound measurements, end-expiratory diaphragm thickness decreased in both, septic and non-septic patients. The 28-day mortality was higher in patients with decrease or no change in diaphragm function. CONCLUSION: Septic patients were associated with a more severe but reversible impaired diaphragm function as compared to non-septic patients. Increase in diaphragm function was associated with a better survival.
RESUMEN
Bone and joint infections (BJIs) are complex infections that require precise microbiological documentation to optimize antibiotic therapy. Currently, diagnosis is based on microbiological culture, sometimes complemented by amplification and sequencing of the 16S rDNA gene. Clinical metagenomics (CMg), that is, the sequencing of the entire nucleic acids in a sample, was previously shown to identify bacteria not detected by conventional methods, but its actual contribution to the diagnosis remains to be assessed, especially with regard to 16S rDNA sequencing. In the present study, we tested the performance of CMg in 34 patients (94 samples) with suspected BJIs, as compared to culture and 16S rDNA sequencing. A total of 94 samples from 34 patients with suspicion of BJIs, recruited from two sites, were analyzed by (i) conventional culture, (ii) 16S rDNA sequencing (Sanger method), and (iii) CMg (Illumina Technology). Two negative controls were also sequenced by CMg for contamination assessment. Based on the sequencing results of negative controls, 414 out of 539 (76.7%) bacterial species detected by CMg were considered as contaminants and 125 (23.2%) as truly present. For monomicrobial infections (13 patients), the sensitivity of CMg was 83.3% as compared to culture, and 100% as compared to 16S rDNA. For polymicrobial infections (13 patients), the sensitivity of CMg was 50% compared to culture, and 100% compared to 16S rDNA. For samples negative in culture (8 patients, 21 samples), CMg detected 11 bacteria in 10 samples from 5 different patients. In 5/34 patients, CMg brought a microbiological diagnosis where conventional methods failed, and in 16/34 patients, CMg provided additional information. Finally, 99 antibiotic resistance genes were detected in 24 patients (56 samples). Provided sufficient genome coverage (87.5%), a correct inference of antibiotic susceptibility was achieved in 8/8 bacteria (100%). In conclusion, our study demonstrated that the CMg provides complementary and potentially valuable data to conventional methods of BJIs diagnosis.
RESUMEN
METHODS: Patients transplanted at our institution provided fecal samples before, and 3-9 months after KT. Fecal bacterial DNA was extracted and 9 bacteria or bacterial groups were quantified by qPCR. RESULTS: 50 patients (19 controls without diabetes, 15 who developed New Onset Diabetes After Transplantation, NODAT, and 16 with type 2 diabetes before KT) were included. Before KT, Lactobacillus sp. tended to be less frequently detected in controls than in those who would become diabetic following KT (NODAT) and in initially diabetic patients (60%, 87.5%, and 100%, respectively, p = 0.08). The relative abundance of Faecalibacterium prausnitzii was 30 times lower in initially diabetic patients than in controls (p = 0.002). The relative abundance of F. prausnitzii of NODAT patients was statistically indistinguishable from controls and from diabetic patients. The relative abundance of Lactobacillus sp. increased following KT in NODAT and in initially diabetic patients (20-fold, p = 0.06, and 25-fold, p = 0.02, respectively). In contrast, the proportion of Akkermansia muciniphila decreased following KT in NODAT and in initially diabetic patients (2,500-fold, p = 0.04, and 50,000-fold, p<0.0001, respectively). The proportion of Lactobacillus and A. muciniphila did not change in controls between before and after the transplantation. Consequently, after KT the relative abundance of Lactobacillus sp. was 25 times higher (p = 0.07) and the relative abundance of A. muciniphila was 2,000 times lower (p = 0.002) in diabetics than in controls. CONCLUSION: An alteration of the gut microbiota composition involving Lactobacillus sp., A. muciniphila and F. prausnitzii is associated with the glycemic status in KT recipients, raising the question of their role in the genesis of NODAT.
Asunto(s)
ADN Bacteriano/genética , Diabetes Mellitus Tipo 2/microbiología , Microbioma Gastrointestinal/genética , Trasplante de Riñón/efectos adversos , Akkermansia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Faecalibacterium prausnitzii/genética , Faecalibacterium prausnitzii/aislamiento & purificación , Faecalibacterium prausnitzii/metabolismo , Heces/microbiología , Femenino , Humanos , Lactobacillus/genética , Lactobacillus/aislamiento & purificación , Lactobacillus/metabolismo , Masculino , Persona de Mediana Edad , Factores de Riesgo , Verrucomicrobia/genética , Verrucomicrobia/aislamiento & purificación , Verrucomicrobia/metabolismoRESUMEN
BACKGROUND: While no data support this practice, international guidelines recommend the removal of totally implanted venous access ports (TIVAPs) in patients with suspicion of TIVAP-related bloodstream infection admitted in the intensive care unit (ICU) for a life-threatening sepsis. METHODS: During this multicenter, retrospective and observational study, we included all patients admitted in five ICU for a life-threatening sepsis in whom a TIVAP was removed between January 2012 and December 2014. We aimed (1) at determining the proportion of confirmed TIVAP-related infections and (2) at assessing short- and long-term survival of patients with and without TIVAP-related infections. RESULTS: One hundred and fifty-one patients (58 ± 14 years, 62% males) were included between 2012 and 2014. TIVAP-related infections were confirmed in 68 patients (45%). Demographic characteristics were similar between patients with and without TIVAP-related infections. SOFA score on admission per point increase [odd ratio (OR), 0.86 interval confidence (IC) 95% (0.8-0.9), p < 0.01] and local signs of infection [OR 4.0, IC 95% (1.1-15.6), p = 0.04] were significantly associated with TIVAP-related infection. Patients with TIVAP-related infection had lower ICU and 6-month mortality as compared to their counterparts (9 vs. 40%, respectively, p < 0.01; and 50 vs. 66%, respectively, p = 0.04). TIVAP-related infection was significantly associated with ICU survival [OR 0.2, IC 95% (0.05-0.5), p < 0.01]. CONCLUSIONS: TIVAP-related infection was confirmed in nearly one out of two cases of life-threatening sepsis in patients in whom it has been removed. TIVAP-related infection was associated with a good prognosis, as compared to patients with other causes of infection.
RESUMEN
BACKGROUND: Escherichia coli strains causing Urinary Tract Infections (UTI) have a fecal origin. METHODS: A fecal sample was collected before Kidney Transplantation (KT) and concomitantly with urine at each of the 15 E. coli UTIs which occurred in 11 KT recipients. Unique E. coli strains were identified among 25 isolates per feces and 5 isolates per urinary sample by random amplification of polymorphic DNA. Phylogenetic group (which is correlated to virulence in the E. coli species) was determined for each E. coli strain by a PCR based method. RESULTS: Forty-three unique fecal strains and 14 unique urinary strains were identified among 650 fecal isolates and 75 urinary isolates. Urinary strains frequently (55% of the cases) belonged to a phylogroup usually not linked to virulence. They were detected in the feces collected concomitantly in 60% of the cases. Urinary strains belonging to a phylogroup usually linked to virulence were more frequently dominant in the feces (100%) than urinary strains belonging to a non-pathogenic phylogroup (42%; P<0.05). Vesical catheter was a facilitating factor only for urinary strains belonging to non-pathogenic phylogroups. Thirty-three percent of the fecal strains were persisting in two consecutive fecal samples and 62% were detected for the first time at the UTI. Numerous pathway lead to UTIs: from a unique, virulent and persisting strain to a non-virulent recently acquired strain facilitated by a vesical catheter. CONCLUSION: Our work shows the diversity of host-microbial interactions which precede extra-intestinal virulence.