The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety ...of targeted and biological therapies.
To review, from an infectious diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3–targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors, and to suggest preventive recommendations.
Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family.
T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death (PD)-1/PD-1 ligand 1 (PD-L1)-targeted agents do not appear to intrinsically increase the risk of infection but can induce immune-related adverse effects requiring additional immunosuppression. Although CD4+ T-cell lymphopenia is associated with alefacept, no opportunistic infections have been observed. Progressive multifocal leukoencephalopathy (PML) may occur during therapy with natalizumab (anti–α4-integrin monoclonal antibody (mAb)) and efalizumab (anti-CD11a mAb), but no cases have been reported to date with vedolizumab (anti-α4β7 mAb). In patients at high risk for PML (positive anti-JC polyomavirus serology with serum antibody index >1.5 and duration of therapy ≥48 months), the benefit–risk ratio of continuing natalizumab should be carefully considered. Fingolimod induces profound peripheral blood lymphopenia and increases the risk of varicella zoster virus (VZV) infection. Prophylaxis with (val)acyclovir and VZV vaccination should be considered. Proteasome inhibitors also increase the risk of VZV infection, and antiviral prophylaxis with (val)acyclovir is recommended. Anti-Pneumocystis prophylaxis may be considered in myeloma multiple patients with additional risk factors (i.e. high-dose corticosteroids).
Clinicians should be aware of the risk of immune-related adverse effects and PML in patients receiving immune checkpoint and cell adhesion inhibitors respectively.
Bacteria are the leading cause of infections after solid organ transplantation. In recent years, a progressive growth in the incidence of multidrug-resistant (MDR) and extensively-drug-reistant (XDR) ...strains has been observed. While methicillin-resistant Staphylococcus aureus (MRSA) infection is declining in non-transplant and SOT patients worldwide, vancomycin-resistant enterococci, MDR/XDR Enterobacteriaceae and MDR/XDR non-fermenters are progressively growing as a cause of infection in solid organ transplant (SOT) patients and represent a global threat. Some SOT patients develop recurrent infections, related to anatomical defects in many cases, which are difficult to treat and predispose patients to the acquisition of MDR pathogens. As the antibiotics active against MDR bacteria have several limitations for their use, which include less clinical experience, higher incidence of adverse effects and less knowledge of the pharmacokinetics of the drug, and, in most cases, are only available for parenteral administration, it is mandatory to know the main characteristics of these drugs to safely treat SOT patients with MDR bacterial infections. Nonetheless, preventive measures are the cornerstone of controlling the spread of these pathogens. Thus, applying the Center for Disease Control and Prevention’s and the European Society of Clinical Microbiology and Infectious Diseases’s recommended antibiotic policies and strategies to control the transmission of MDR strains in the hospital setting is essential for the management of SOT patients.
The aim of this study was to assess changes in antibiotic resistance, epidemiology and outcome among patients with Enterococcus faecalis infective endocarditis (EFIE) and to compare the efficacy and ...safety of the combination of ampicillin and gentamicin (A+G) with that of ampicillin plus ceftriaxone (A+C). The study was a retrospective analysis of a prospective cohort of EFIE patients treated in our centre from 1997 to 2011. Thirty patients were initially treated with A+G (ampicillin 2 g/4 h and gentamicin 3 mg/kg/day) and 39 with A+C (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) for 4–6 weeks. Increased rates of high-level aminoglycoside resistance (HLAR; gentamicin MIC ≥512 mg/L, streptomycin MIC ≥1024 mg/L or both) were observed in recent years (24% in 1997–2006 and 49% in 2007–2011; p 0.03). The use of A+C increased over time: 1997–2001, 4/18 (22%); 2002–2006, 5/16 (31%); 2007–2011, 30/35 (86%) (p <0.001). Renal failure developed in 65% of the A+G group and in 34% of the A+C group (p 0.014). Thirteen patients (43%) in the A+G group had to discontinue treatment, whereas only one patient (3%) treated with A+C had to discontinue treatment (p <0.001). Only development of heart failure and previous chronic renal failure were independently associated with 1-year mortality, while the individual antibiotic regimen (A+C vs. A+G) did not affect outcome (OR, 0.7; 95% CI, 0.2–2.2; p 0.549). Our study shows that the prevalence of HLAR EFIE has increased significantly in recent years and that alternative treatment with A+C is safer than A+G, with similar clinical outcomes, although the sample size is too small to draw firm conclusions. Randomized controlled studies are needed to confirm these results.
Background
Urinary tract infection (UTI) is the most common infection in renal transplant patients, but it is necessary to determine the risk factors for bacterial UTI in recipients of other solid ...organ transplants (SOTs), as well as changes in etiology, clinical presentation, and prognosis.
Methods
In total, 4388 SOT recipients were monitored in 16 transplant centers belonging to the Spanish Network for Research on Infection in Transplantation (RESITRA). The frequency and characteristics of bacterial UTI in transplant patients were obtained prospectively from the cohort (September 2003 to February 2005).
Results
A total of 192 patients (4.4%) presented 249 episodes of bacterial UTI (0.23 episodes per 1000 transplantation days); 156 patients were kidney or kidney–pancreas transplant recipients, and 36 patients were liver, heart, and lung transplant recipients. The highest frequency was observed in renal transplants (7.3%). High frequency of cystitis versus pyelonephritis without related mortality was observed in both groups. The most frequent etiology was Escherichia coli (57.8%), with 25.7% producing extended‐spectrum β‐lactamase (ESBL). In all transplants but renal, most cases occurred in the first month after transplantation. Cases were uniformly distributed during the first 6 months after transplantation in renal recipients. Age (odds ratio OR per decade 1.1, 95% confidence interval CI 1.02–1.17), female gender (OR 1.74, 95% CI 1.42–2.13), and the need for immediate post‐transplant dialysis (OR 1.63, 95% CI 1.29–2.05) were independent variables associated with bacterial UTI in renal and kidney–pancreas recipients. The independent risk factors identified in non‐renal transplants were age (OR per decade 1.79, 95% CI 1.09–3.48), female gender (OR 1.7, 95% CI 1.43–2.49), and diabetes (OR 1.02, 95% CI 1.001–1.040).
Conclusions
UTI was frequent in renal transplants, but also not unusual in non‐renal transplants. Because E. coli continues to be the most frequent etiology, the emergence of ESBL‐producing strains has been identified as a new problem. In both populations, most cases were cystitis without related mortality. Although the first month after transplantation was a risk period in all transplants, cases were uniformly distributed during the first 6 months in renal transplants. Age and female gender were identified as risk factors for UTI in both populations. Other particular risk factors were the need for immediate post‐transplant dialysis in renal transplants and diabetes in non‐renal transplants.
HgCdTe (MCT) is a very versatile material system for infrared (IR) detection, suitable for high performance detection in a wide range of applications and spectral ranges. Indeed, the ability to ...tailor the cutoff frequency as close as possible to the needs makes it a perfect candidate for high performance detection. Moreover, the high quality material available today, grown either by molecular beam epitaxy or liquid phase epitaxy, allows for very low dark currents at low temperatures, suitable for low flux detection applications such as science imaging. MCT has also demonstrated robustness to the aggressive environment of space and faces, therefore, a large demand for space applications. A satellite may stare at the earth, in which case detection usually involves a lot of photons, called a high flux scenario. Alternatively, a satellite may stare at outer space for science purposes, in which case the detected photon number is very low, leading to low flux scenarios. This latter case induces very strong constraints onto the detector: low dark current, low noise, (very) large focal plane arrays. The classical structure used to fulfill those requirements are usually
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MCT photodiodes. This type of structure has been deeply investigated in our laboratory for different spectral bands, in collaboration with the CEA Astrophysics lab. However, another alternative may also be investigated with low excess noise: MCT
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avalanche photodiodes (APD). This paper reviews the latest achievements obtained on this matter at DEFIR (LETI and Sofradir common laboratory) from the short wave infrared (SWIR) band detection for classical astronomical needs, to long wave infrared (LWIR) band for exoplanet transit spectroscopy, up to very long wave infrared (VLWIR) bands. The different available diode architectures (
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VHg or
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, or even APDs) are reviewed, including different available ROIC architectures for low flux detection.
We sought to determine the frequency, risk factors, and clinical impact of recurrent urinary tract infections (UTI) in kidney transplant recipients. Of 867 patients who received a kidney transplant ...between 2003 and 2010, 174 (20%) presented at least one episode of UTI. Fifty‐five patients presented a recurrent UTI (32%) and 78% of them could be also considered relapsing episodes. Recurrent UTI was caused by extended‐spectrum betalactamase (ESBL)–producing Klebsiella pneumoniae (31%), followed by non‐ESBL producing Escherichia coli (15%), multidrug‐resistant (MDR) Pseudomonas aeruginosa (14%), and ESBL‐producing E. coli (13%). The variables associated with a higher risk of recurrent UTI were a first or second episode of infection by MDR bacteria (OR 12; 95%CI 528), age >60 years (OR 2.2; 95%CI 1.15.1), and reoperation (OR 3; 95%CI 1.37.1). In addition, more relapses were recorded in patients with UTI caused by MDR organisms than in those with susceptible microorganisms. There were no differences in acute rejection, graft function, graft loss or 1 year mortality between groups. In conclusion, recurrent UTI is frequent among kidney recipients and associated with MDR organism. Classic risk factors for UTI (female gender and diabetes) are absent in kidney recipients, thus highlighting the relevance of uropathogens in this population.
A study of kidney transplant recipients shows that 20% presented at least one episode of urinary tract infection, of which a third had recurrent infection, with multi‐drug‐resistant bacteria being the most important risk factor for recurrence.
Urinary tract infections (UTIs) are frequent after renal transplantation, but their impact on short-term graft outcome is not well established. All kidney transplants performed between July 2003 and ...December 2010 were investigated to evaluate the impact of UTI on graft function at 1 year after transplantation. Of 867 patients who received a kidney transplant, 184 (21%) developed at least one episode of UTI, at a median of 18 days after transplantation. The prevalence of acute graft pyelonephritis (AGP) was 15%. The most frequent pathogens identified were Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa, 37% of which were considered to be multidrug-resistant strains. Thirty-eight patients (4%) lost their grafts, 225 patients (26%) had graft function impairment and the 1-year mortality rate was 3%; however, no patient died as a consequence of a UTI. Surgical re-intervention and the development of at least one episode of AGP were independently associated with 1-year graft function impairment. Moreover, the development of at least one episode of AGP was associated with graft loss at 1 year. Patients with AGP caused by a resistant strain had graft function impairment more frequently, although this difference did not reach statistical significance (53% vs. 36%, p 0.07). Neither asymptomatic bacteriuria nor acute uncomplicated UTI were associated with graft function impairment in multivariate analysis. To conclude, UTIs are frequent in kidney transplant recipients, especially in the early post-transplantation period. Although AGP was significantly associated with kidney graft function impairment and 1-year post-transplantation graft loss, lower UTIs did not affect graft function.
Background
Clinical management in orthogeriatric units and outcome indicators are similar for extracapsular fragility hip fractures, without discriminating between subtrochanteric and pertrochanteric ...fractures.
Hypothesis
Geriatric patients, 75 years or older, with subtrochanteric fractures have worse clinical and functional outcomes than those with pertrochanteric fractures.
Materials and methods
Retrospective observational study of data prospectively collected by the Spanish Hip Fracture Registry including patients 75 years or older, admitted for extracapsular hip fractures from January 2017 to June 2019. Demographic and baseline status, pre-operative, post-operative and 30-day follow-up data were included.
Results
A total of 13,939 patients with extracapsular hip fractures were registered: 12,199 (87.5%) pertrochanteric and 1740 (12.5%) subtrochanteric. At admission, patients with subtrochanteric fractures were younger (86.5 ± 5.8 versus 87.1 ± 5.6 years old), had better pre-fracture mobility (3.7 ± 2.7 versus 3.9 ± 2.8) (1-to-10 scale, 1 being independent) and were more likely to be living at home; those with pertrochanteric fractures had worse cognitive function (Pfeiffer 3.3 ± 3.3 versus 3.8 ± 3.5). The subtrochanteric fracture group showed worse post-fracture mobility (7.3 ± 2.7 versus 6.7 ± 2.7) and greater deterioration of mobility (3.7 ± 3.0 versus 2.9 ± 2.7). Among individuals living at home at baseline, those with subtrochanteric fractures were more likely to remain in an assisted facility at 30-day follow-up. In-hospital mortality during acute admission was higher for the subtrochanteric group (5.6% versus 4.5%) (
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= 0.028). To our knowledge, this is the first paper highlighting the differences between these two fracture groups in the geriatric population.
Conclusions
Subtrochanteric fractures in the older population are a different and worse entity, with greater morbimortality and functional decline than pertrochanteric fractures. Despite being younger and fitter at admission, older patients with subtrochanteric fractures have a higher risk of remaining non-weight bearing and undergoing re-operation and institutionalization. Orthogeriatric units should be aware of this and manage subtrochanteric fractures accordingly.
Level of evidence: IV.
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