Objective
To evaluate the real‐world clinical efficacy of ceftolozane/tazobactam (C/T) in difficult‐to‐treat infections caused by multi‐drug resistant Gram‐negative microorganisms, including ...carbapenem‐resistant Pseudomonas aeruginosa.
Methods
Retrospective cohort study of adult patients treated with C/T for at least 48 hours for infections caused by multi‐drug resistant Gram‐negative bacteria in a tertiary hospital from May 2016 until August 2019. The primary outcome analysed was clinical failure, defined as a composite of symptomatology persistence after 7 days of C/T treatment, infection recurrence, and/or all‐cause mortality within 30 days of follow‐up.
Results and discussion
96 episodes of C/T treatment were included, mostly consisting of targeted treatments (83.9%) for the following sources of infection: intra‐abdominal (22.6%), urinary tract (25.8%), skin and soft tissue (19.4%), hospital‐acquired pneumonia (14%), and other (6.4%). The most frequently isolated bacteria were carbapenem‐resistant (88, 94.6%). Clinical failure rate was 30.1%, due to persistent infection at day 7 (4.3%), recurrence of the initial infection (16.1%), or 30‐day all‐cause mortality (8.6%). Adverse events most frequently reported were Clostridium difficile infection (9%) and cholestasis (8%).
What is new and conclusion
C/T showed a favourable clinical profile for difficult‐to‐treat multidrug‐resistant and carbapenem‐resistant Gram‐negative infections, regardless of the source of infection.
This study provides real‐world data regarding the use of C/T to treat Gram‐negative MDR severe infections. We found that C/T was effective and well tolerated in the treatment of difficult‐to‐treat MDR and carbapenem‐resistant Gram‐negative infections, regardless of the source of infection.
Background
Systematic screening for, and treatment of, latent tuberculosis (TB) infection is recommended prior to kidney transplant. However, little is known about patient compliance with, or the ...safety profile of, preventive therapies used in clinical practice.
Methods
This was a retrospective observational study of patients who were eligible for kidney transplant and were evaluated for TB infection between January 2013 and June 2019 at the TB clinic of a tertiary care teaching hospital. All patient data were registered prospectively as part of our nurse‐led program before kidney transplant. We assessed completion rates, tolerance with therapy, development of TB, and associated workload.
Results
In total, 1568 patients were referred to our TB clinic for evaluation. Preventive therapy was given to 385 patients and completed by 340 (88.3%). Of these, 89 (23.1%) experienced some intolerance, with 27 requiring full discontinuation. After a median follow‐up of 45 months (1426 patient‐years), 206 (53.5%) of the treated patients received a kidney transplant; only one patient, who failed to complete treatment, developed post‐transplant TB (7.01 cases per 10 000 patient‐years; 95% confidence interval, 0.35‐34.59). Extra nurse or medical visits were required by 268 (69.6%) patients.
Conclusion
Despite the complexity and workload generated by patients with ESRD awaiting kidney transplant, preventive therapy for TB is effective in most cases. Our experience provides important evidence on the feasibility of preventive therapy for TB before kidney transplant when delivered as part of a comprehensive nurse‐led program.
Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of ...QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments. We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-gamma concentrations between greater than or equal to0.35 and less than or equal to0.99 IU*mL.sup.-1 in one or both QFT-i tubes. In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors.
Retrospective, multinational, 1:2 ...matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections.
Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years interquartile range {IQR} 40-62). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio aOR 1.04; 95 confidence interval CI, 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection.
Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.
Background and purpose Screening for and treatment of latent tuberculosis (TB) in patients with end-stage kidney disease (ESKD) are recommended. However, there is limited evidence on safety and ...treatment completion in this population. The objective of the study is to evaluate three short-course rifamycin-based regimens for the treatment of latent TB in ESKD patients. Methods Study design and setting. This is a prospective, open label, randomized clinical trial, that will be conducted at seven teaching hospitals in Spain. Study population, randomization, and interventions. Consecutive adult patients with ESKD requiring treatment for a latent TB infection will be randomly allocated (1:1:1) to receive one of the three treatment regimens of the study: three months of daily isoniazid plus rifampicin (3HR); three months of once-weekly isoniazid plus rifapentine (3HP); or four months of daily rifampicin (4R). Participants will be followed regularly through pre-established visits and a blood test schedule from enrolment to a month after finishing the assigned treatment. Outcomes. The primary outcome will be treatment completion, while the secondary outcomes will be discontinuation of the assigned treatment due to adverse events, related or unrelated to the study treatment; definitive discontinuation of the assigned treatment because of adverse events related to the treatment of the study, and death. Sample size. Two hundred and twenty-five subjects (75 per arm) will be enrolled, which will enable the demonstration, if it exists, of an increase of 0.16 in treatment completion rates either in the 3HP or 4R arm with respect to the 3HR arm. Discussion Results of this clinical trial will contribute to evidence-based recommendations on the management of latent TB infection in ESKD patients. Trial registration ClinicalTrials.gov identifier: NCT05021731.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB2-TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD8
T-cell ...response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-γ) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases IMID), and indeterminate (89 asylum seekers or people from abroad ASPFA) risks of recent TB exposure. A TB2-TB1 value >0.6 IU·ml
was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (
= 0.591). The adjusted odds ratios (aORs) for an association between a TB2-TB1 result of >0.6 IU·ml
and risk of recent exposure versus contacts were 0.71 (95% confidence interval CI, 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (
= 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2-TB1 difference of >0.6 IU·ml
was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection.
Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-γ) release assay, a difference in IFN-γ production between the two antigen tubes (TB2 minus TB1) of >0.6 IU·ml
could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN-γ in TB1 and TB2 tubes that were higher than 0.6 IU·ml
. QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing.
A pro-inflammatory phenotype has been related to psychotic disorders. The neutrophil-lymphocyte ratio (NLR) is an accessible biomarker that could be helpful to characterize this systemic inflammation ...state.
This study evaluated the NLR in a cohort of 310 subjects with a first episode of psychosis (FEP) and a matched group of 215 healthy controls, recruited in 16 Spanish centers participating in the PEPs Project. We investigated the NLR measures over 2 years in a prospective, naturalistic study.
At baseline, the FEP group showed a significant higher mean NLR compared to the control group (1.96 ± 1.11 vs 1.72 ± 0.74, P = 0.03). These ratio differences between groups grew at the 24 months follow-up visit (2.04 ± 0.86 vs 1.65 ± 0.65, P < 0.001). Within the FEP group, there were no significant differences in NLR across the follow-up visits, between genders or diagnosis groups (affective vs nonaffective). NLR values did not correlate with the Positive and Negative Symptoms Scale scores. The group of patients who did not reach remission criteria at the end of the study showed a significant higher NLR than those who remitted (2.1896 ± 0.85 vs 1.95 ± 0.87, P = 0.042). A significant correlation between antipsychotic doses and NLR was found at the two-years follow-up visit (r=0.461, P < 0.001).
Our results highlight the existence of an underlying predisposition of FEP patients to present an increased mean NLR. The use of NLR in clinical practice could be helpful to identify this inflammatory imbalance.
Background. The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and ...1-y mortality of these patients. Methods. Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases. Results. In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40–62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval 1.1-9.77; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 4–42 versus 11 3–21 d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 95% CI, 0.41-4.43, P = 0.618) did not differ between survivors and those who died. Conclusions. NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality.
No tillage management is being encouraged nowadays to prevent soil erosion and contribute to carbon (C) sequestration. However, N fertilizer should be managed properly to optimize N use efficiency ...and to avoid the side-effects of losses of gaseous nitrogen (N), particularly those of ammonia (NH3), which are expected to increase due to the presence of residues in the topsoil. In this context, a non-tilled (two years after conversion from tillage) field experiment was set up in central Spain, in which urea treated with a combination of urease (N-butyl thiophosphorictriamide, NBPT) and nitrification (2-(3,4-dimethyl-1H-pyrazol-1-yl) succinic acid isomeric mixture, DMPSA) inhibitors was compared with the use of urea without inhibitors. Fluxes of NH3 (using the integrated horizontal flux method with three replicates), nitrous oxide (N2O), methane (CH4) and soil respiration were measured throughout the wheat (Triticum aestivum L.) cropping cycle under rainfed conditions, together with ancillary soil measurements (e.g., soil moisture and mineral N), yield and crop uptake of N. Gaseous N losses from urea without inhibitors accounted for 10.35% and 0.66% (for NH3 and N2O, respectively) of total N applied. The use of the double inhibitor resulted in a significant mitigation of both losses (by 50.5% and 91.6% for NH3 and N2O, respectively). The double inhibitor increased N use efficiency expressed as crop recovery efficiency and partial nutrient balance, and decreased N surplus, in comparison with urea without inhibitors. In spite of a similar grain yield, the unfertilized control had the lowest aboveground N uptake rate, due to the higher concentrations of grain and straw N for the fertilized treatments. Under the conditions of our study, NH3 volatilization in a short-term no-till managed field can be minimized using a double (urease plus nitrification) inhibitor. This strategy had no negative side effects on N surplus, CH4 uptake or N2O mitigation and led to a significant improvement of N use efficiency.
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•The use of the DMPSA + NBPT inhibitor reduced NH3 volatilization rates under rainfed no-till (short-term) conditions.•The double inhibitor decreased N2O losses by 91.6% in comparison with urea alone.•The double inhibitor tended to increase CH4 uptake and temporarily decreased respiration fluxes.•Soil rewetting episodes were relevant for the N2O, CH4 and CO2 fluxes.•The double inhibitor significantly improved N use efficiency and mitigated N surplus.
To analyse the overall effectiveness and cost-efficiency of a mobile application (APP) as a community health asset (HA) with recommendations and recovery exercises created bearing in mind the main ...symptoms presented by patients in order to improve their quality of life, as well as other secondary variables, such as the number and severity of ongoing symptoms, physical and cognitive functions, affective state, and sleep quality.
The first step was to design and develop the technologic community resource, the APP, following the steps involved in the process of recommending health assets (RHA). After this, a protocol of a randomised clinical trial for analysing its effectiveness and cost-efficiency as a HA was developed. The participants will be assigned to: (1st) usual treatment by the primary care practitioner (TAU), as a control group; and (2nd) TAU + use of the APP as a HA and adjuvant treatment in their recovery + three motivational interviews (MI), as an interventional group. An evaluation will be carried out at baseline with further assessments three and six months following the end of the intervention.
Although research and care for these patients are still in their initial stages, it is necessary to equip patients and health care practitioners with tools to assist in their recovery. Furthermore, enhanced motivation can be achieved through telerehabilitation (TR).
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