Tobramycin Systemic Absorption in Lung Transplant Recipients Treated With Inhaled Tobramycin: A Cohort Study.

Inhaled tobramycin treatment has been associated with nephrotoxicity in some case reports, but limited data are available about serum levels and its possible systemic absorption in lung transplant recipients (LTR). We conducted a single-center, observational and retrospective study of all adult (>18 years old) LTR treated with inhaled tobramycin for at least 3 days between June 2019 and February 2022. Trough serum levels were collected and >2 µg/mL was considered a high drug level. The primary outcome assessed the presence of detectable trough levels, while the secondary outcome focused on the occurrence of acute kidney injury (AKI) in individuals with detectable trough levels. Thirty-four patients, with a median age of 60 years, were enrolled. The primary indications for treatment were donor bronchial aspirate bacterial isolation (18 patients) and tracheobronchitis (15 patients). In total, 28 patients (82%) exhibited detectable serum levels, with 9 (26%) presenting high levels (>2 µg/mL). Furthermore, 9 patients (26%) developed acute kidney injury during the treatment course. Median trough tobramycin levels were significantly elevated in invasively mechanically ventilated patients compared to non-ventilated individuals (2.5 µg/mL vs. 0.48 µg/mL) (p < 0.001). Inhaled tobramycin administration in LTRs, particularly in those requiring invasive mechanical ventilation, may result in substantial systemic absorption.

In Vitro Antibacterial Activity of Silver Nanoparticles Conjugated with Amikacin and Combined with Hyperthermia against Drug-Resistant and Biofilm-Producing Strains.

In view of the current increase and spread of antimicrobial resistance (AMR), there is an urgent need to find new strategies to combat it. This study had two aims. First, we synthesized highly monodispersed silver nanoparticles (AgNPs) of approximately 17 nm, and we functionalized them with mercaptopoly(ethylene glycol) carboxylic acid (mPEG-COOH) and amikacin (AK). Second, we evaluated the antibacterial activity of this treatment (AgNPs_mPEG_AK) alone and in combination with hyperthermia against planktonic and biofilm-growing strains. AgNPs, AgNPs_mPEG, and AgNPs_mPEG_AK were characterized using a suite of spectroscopy and microscopy methods. Susceptibility to these treatments and AK was determined after 24 h and over time against 12 clinical multidrug-resistant (MDR)/extensively drug-resistant (XDR) isolates of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The efficacy of the treatments alone and in combination with hyperthermia (1, 2, and 3 pulses at 41°C to 42°C for 15 min) was tested against the same planktonic strains using quantitative culture and against one P. aeruginosa strain growing on silicone disks using confocal laser scanning microscopy. The susceptibility studies showed that AgNPs_mPEG_AK was 10-fold more effective than AK alone, and bactericidal efficacy after 4, 8, 24, or 48 h was observed against 100% of the tested strains. The combination of AgNPs_mPEG_AK and hyperthermia eradicated 75% of the planktonic strains and exhibited significant reductions in biofilm formation by P. aeruginosa in comparison with the other treatments tested, except for AgNPs_mPEG_AK without hyperthermia. In conclusion, the combination of AgNPs_mPEG_AK and hyperthermia may be a promising therapy against MDR/XDR and biofilm-producing strains. IMPORTANCE Antimicrobial resistance (AMR) is one of the greatest public health challenges, accounting for 1.27 million deaths worldwide in 2019. Biofilms, a complex microbial community, directly contribute to increased AMR. Therefore, new strategies are urgently required to combat infections caused by AMR and biofilm-producing strains. Silver nanoparticles (AgNPs) exhibit antimicrobial activity and can be functionalized with antibiotics. Although AgNPs are very promising, their effectiveness in complex biological environments still falls below the concentrations at which AgNPs are stable in terms of aggregation. Thus, improving the antibacterial effectiveness of AgNPs by functionalizing them with antibiotics may be a significant change to consolidate AgNPs as an alternative to antibiotics. It has been reported that hyperthermia has a large effect on the growth of planktonic and biofilm-producing strains. Therefore, we propose a new strategy based on AgNPs functionalized with amikacin and combined with hyperthermia (41°C to 42°C) to treat AMR and biofilm-related infections.

Methicillin-Susceptible Staphylococcus aureus Biofilm Formation on Vascular Grafts: an In Vitro Study.

The aim of this study was to quantify in vitro biofilm formation by methicillin-susceptible Staphylococcus aureus (MSSA) on the surfaces of different types of commonly used vascular grafts. We performed an in vitro study with two clinical strains of MSSA (MSSA2 and MSSA6) and nine vascular grafts: Dacron (Hemagard), Dacron-heparin (Intergard heparin), Dacron-silver (Intergard Silver), Dacron-silver-triclosan (Intergard Synergy), Dacron-gelatin (Gelsoft Plus), Dacron plus polytetrafluoroethylene (Fusion), polytetrafluoroethylene (Propaten; Gore), Omniflow II, and bovine pericardium (XenoSure). Biofilm formation was induced in two phases: an initial 90-minute adherence phase and a 24-hour growth phase. Quantitative cultures were performed, and the results were expressed as log10 CFU per milliliter. The Dacron-silver-triclosan graft and Omniflow II were associated with the least biofilm formation by both MSSA2 and MSSA6. MSSA2 did not form a biofilm on the Dacron-silver-triclosan graft (0 CFU/mL), and the mean count on the Omniflow II graft was 3.89 CFU/mL (standard deviation [SD] 2.10). The mean count for the other grafts was 7.01 CFU/mL (SD 0.82). MSSA6 formed a biofilm on both grafts, with 2.42 CFU/mL (SD 2.44) on the Dacron-silver-triclosan graft and 3.62 CFU/mL (SD 2.21) on the Omniflow II. The mean biofilm growth on the remaining grafts was 7.33 CFU/mL (SD 0.28). The differences in biofilm formation on the Dacron-silver-triclosan and Omniflow II grafts compared to the other tested grafts were statistically significant. Our findings suggest that of the vascular grafts we studied, the Dacron-silver-triclosan and Omniflow II grafts might prevent biofilm formation by MSSA. Although further studies are needed, these grafts seem to be good candidates for clinical use in vascular surgeries at high risk of infections due to this microorganism. IMPORTANCE The Dacron silver-triclosan and Omniflow II vascular grafts showed the greatest resistance to in vitro methicillin-susceptible Staphylococcus aureus biofilm formation compared to other vascular grafts. These findings could allow us to choose the most resistant to infection prosthetic graft.

Hyperthermia Prevents In Vitro and In Vivo Biofilm Formation on Endotracheal Tubes.

There is currently an urgent need to find new strategies to tackle antimicrobial resistance and biofilm-related infections. This study has two aims. First, we evaluated the in vitro efficacy of hyperthermia in preventing biofilm formation on the surfaces of polyvinyl chloride discs. Second, we assessed the in vivo efficacy of hyperthermia in preventing biofilm formation in endotracheal tubes (ETTs) of a rabbit model. For the in vitro studies, nine clinical extensively drug-resistant/multidrug-resistant Gram-negative isolates of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa and three clinical methicillin-resistant Staphylococcus aureus strains were studied. For biofilm formation, an adhesion step of 30 or 90 min followed by a growth step of 24 h were performed with application of one, two, and three pulses at 42°C for 15 min each pulse after the adhesion step. For the in vivo studies, New Zealand rabbits were intubated with ETTs previously colonized with K. pneumoniae or P. aeruginosa strains, and three pulses at 42°C for 15 min were applied after the adhesion step. The application of three pulses at 42°C for 15 min each pulse was needed to achieve the prevention of the in vitro biofilm formation of 100% of the tested strains. The application of heat pulses in a rabbit intubation model led to biofilm prevention of 85% against two K. pneumoniae strains and 80% against two P. aeruginosa strains compared to the control group. Hyperthermia application through pulses at 42°C could be a new nonantibiotic strategy to prevent biofilm formation in ETTs. IMPORTANCE Biofilm-producing microorganisms are considered medically crucial since they cause 80% of the infections that occur in the human body. Medical devices such as endotracheal tubes (ETTs) can act as a reservoir for pathogens providing the surface to which microorganisms can adhere and cause biofilm-associated infections in critically ill patients. This biofilm has been related with the development of ventilator-associated pneumonia (VAP), with an incidence of 8 to 28%, a mortality rate up to 17% and its associated high extra costs. Although some VAP-preventive measures have been reported, they have not demonstrated a significant reduction of VAP incidence. Therefore, we present a new nonantibiotic strategy based on hyperthermia application to prevent biofilm formation inside ETTs. This technology could reduce VAP incidence, intubation duration, hospital and intensive care unit (ICU) length stays, and mortality rates. Consequently, this could decrease the antibiotics administered and influence the impact of antibiotic resistance in the ICU.

In Vitro and In Vivo Antimicrobial Activity of Hypochlorous Acid against Drug-Resistant and Biofilm-Producing Strains.

The aims of this study were as follows. First, we determined the antimicrobial efficacy of hypochlorous acid (HClO) against bacterial, fungal, and yeast strains growing planktonically and growing in biofilms. Second, we sought to compare the activity of the combination of daptomycin and HClO versus those of the antimicrobial agents alone for the treatment of experimental catheter-related Staphylococcus epidermidis infection (CRI) using the antibiotic lock technique (ALT) in a rabbit model. HClO was generated through direct electric current (DC) shots at determined amperages and times. For planktonic susceptibility studies, 1 to 3 DC shots of 2, 5, and 10 mA from 0 to 300 s were applied. A DC shot of 20 mA from 0 to 20 min was applied to biofilm-producing strains. Central venous catheters were inserted into New Zealand White rabbits, inoculated with an S. epidermidis strain, and treated with saline solution or ALT using daptomycin (50 mg/mL), HClO (20 mA for 45 min), or daptomycin plus HClO. One hundred percent of the planktonic bacterial, fungal, and yeast strains were killed by applying one DC shot of 2, 5, and 10 mA, respectively. One DC shot of 20 mA for 20 min was sufficient to eradicate 100% of the tested biofilm-producing strains. Daptomycin plus HClO lock therapy showed the highest activity for experimental CRI with S. epidermidis. HClO could be an effective strategy for treating infections caused by extensively drug-resistant or multidrug-resistant and biofilm-producing strains in medical devices and chronic wounds. The results of the ALT using daptomycin plus HClO may be promising. IMPORTANCE Currently, drug-resistant infections are increasing and there are fewer antibiotics available to treat them. Therefore, there is an urgent need to find new antibiotics and nonantimicrobial strategies to treat these infections. We present a new nonantibiotic strategy based on hypochlorous acid generation to treat long-term catheter-related and chronic wounds infections.

Safety and Effectiveness of Isavuconazole Treatment for Fungal Infections in Solid Organ Transplant Recipients (ISASOT Study).

Isavuconazole (ISA) is an alternative treatment for Aspergillus spp. and other fungal infections, but evidence regarding its use in solid organ transplant recipients (SOTR) is scarce. All SOTR who received ISA for treatment of a fungal infection (FI) at our center from December 2017 to January 2021 were included. The duration of the treatment depended on the type of infection. All patients were followed up to 3 months after treatment. Fifty-three SOTR were included, and the majority (44, 83%) were lung transplant recipients. The most frequently treated FI was tracheobronchitis (25, 46.3%). Aspergillus spp. (43, 81.1%); specially A. flavus (16, 37.2%) and A. fumigatus (12, 27.9%), was the most frequent etiology. Other filamentous fungi including one mucormycosis, and four yeast infections were treated. The median duration of treatment was 81 days (IQR 15-197). Mild gamma-glutamyltransferase elevation was the most frequent adverse event (34%). ISA was prematurely discontinued in six patients (11.3%) due to mild hepatotoxicity (2), fatigue (2), gastrointestinal intolerance (1) and myopathy (1). The mean tacrolimus dose decrease was 30% after starting ISA. Seven patients received ISA with mTOR inhibitors with good tolerability. Two patients developed breakthrough FI (3.8%). Among patients who completed the treatment, 27 (50.9%) showed clinical cure and 15 (34.1%) presented fungal persistence. Three patients (6%) died while on ISA due to FI. ISA was well tolerated and appeared to be an effective treatment for FI in SOTR. IMPORTANCE We describe 53 solid organ transplant recipients treated with isavuconazole for fungal infections. Because its use in clinical practice, there is scarce data of its use in solid organ transplant recipients, where interactions with calcineurin inhibitors and mTOR and adverse drug events have limited the use of other triazoles. To the best of our knowledge, this is the first article describing the safety regarding adverse events and drug interactions of isavuconazole for the treatment of fungal infections in a cohort of solid organ transplant recipients. Also, although this is a noncomparative study, we report some real world effectivity data of these patients, including treatment of non-Aspergillus fungal infections.

COVID-19 in lung transplant recipients: A multicenter study.

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.

Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients.

Hemagglutination-inhibitory antibodies are usually highly strain specific with little effect on infection with drifted or shifted strains. The significance of broadly cross-reactive non-HAI anti-influenza antibodies against conserved domains of virus glycoproteins, such as the hemagglutinin (HA) stalk, is of great interest. We characterize a cohort of 40 H1N1pmd09 influenza-infected patients and identify lower respiratory symptoms (LRSs) as a predictor for development of pneumonia. A binomial logistic regression of log10 pre-existing antibody values shows that the probability of LRS occurrence decreased with increased anti-HA full-length and stalk antibody ELISA titers. However, a multilevel logistic regression model adjusted by other potential serocorrelates demonstrates that only antibodies directed against the stalk of HA correlate with protection from lower respiratory infection, limiting disease progression. Our predictive model indicates that a threshold of protective immunity based on broadly cross-reactive HA stalk antibodies could be feasible.

Effect of Influenza Vaccination Inducing Antibody Mediated Rejection in Solid Organ Transplant Recipients.

Introduction: Our goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR). Methods: Serum anti-Human Leukocyte Antigen (HLA) antibodies were determined using class I and class II antibody-coated latex beads (FlowPRATM Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch. Results: We studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%; P = 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed de novo anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA. Conclusion: Our results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR.

Selection criteria of solid organ donors in relation to infectious diseases: A Spanish consensus.

The immunosuppressive treatment that recipients receive from a solid organ transplantation hinders the defensive response to infection. Its transmission from the donor can cause dysfunction or loss of the graft and even death of the recipient if proper preventive measures are not established. This potential risk should be thoroughly evaluated to minimise the risk of infection transmission from donor to recipient, especially with organ transplantation from donors with infections, without increasing graft dysfunction and morbidity and mortality in the recipient. This document aims to review current knowledge about infection screening in potential donors and offer clinical and microbiological recommendations about the use of organs from donors with infection based on available scientific evidence.

Association between biomass formation and the prognosis of infective endocarditis due to Staphylococcus aureus.

INTRODUCTION: The aim of this study was to evaluate the association between biomass formation and the clinical characteristics and prognosis of Staphylococcus aureus infective endocarditis (IE). METHODS: We prospectively studied 209 S. aureus strains causing IE. Biomass formation was examined using the crystal violet assay and quantified spectrophotometrically. The average (SD) optical density of the biomass was compared for each clinical, microbiological (methicillin-resistance, vancomycin MIC≥1.5µg/ml) and molecular (clonal complex, agr type and agr dysfunction) variable according to their presence or absence. The primary clinical endpoints studied were in-hospital death, severe sepsis, persistent bacteraemia, symptomatic peripheral embolisms and prosthetic valve IE. RESULTS: Mean age was 66.1 years, 61.5% of patients were male and the median age-adjusted Charlson comorbidity index was 5 points (IQR 3-8). In-hospital mortality was 37.3%. Strains belonging to CC5 and CC22 had optical biomass densities [mean (SD) 1.573 (1.14) vs 0.942 (0.98) p<0.001 and 1.720 (0.94) vs 1.028 (1.04) p=0.001, respectively]. Strains belonging to CC5 and CC22 had significantly higher optical biomass densities [1.369 (1.18) vs 0.920 (0.93) p=0.008]. No statistically significant differences were found in the clinical endpoints studied. CONCLUSIONS: High biomass production was associated with CC5 and CC22 but not with higher hospital mortality, septic complications, type of endocarditis, methicillin-resistance, elevated vancomycin MIC or agr dysfunction.

Donor-derived bacterial infections in lung transplant recipients in the era of multidrug resistance.

OBJECTIVES: Our aim was to analyze the prevalence of multidrug-resistant bacterial infections in lung transplant donors and to evaluate its influence on donor-derived bacterial infections. METHODS: We conducted a retrospective study of adult patients who underwent lung transplantation (2013-2016) at our hospital. Donor-derived bacterial infection was defined as the isolation of the same bacteria with identical antibiotic susceptibility patterns in the recipient and the perioperative cultures from the donor during the first month posttransplantation. We utilized a preventive antibiotic strategy adapted to the bacteria identified in donor cultures using systemic and nebulized antibiotics. RESULTS: 252 lung transplant recipients and 243 donors were included. In 138/243 (56.8%) donors, one bacterial species was isolated from at least one sample; graft colonization (118/243; 48.6%), blood cultures (5/243; 2.1%) and the contamination of preservation fluids (56/243; 23%). Multidrug-resistant bacteria were isolated from 12/243 (4.9%) donors; four Enterobacterales, four Stenotrophomonas maltophilia, three Pseudomonas aeruginosa and one methicillin-resistant Staphylococcus aureus. There was no transmission of these multidrug-resistant bacteria. Donor-derived infections, primarily tracheobronchitis due to non-MDR bacteria, were diagnosed in 7/253 (2.9%) recipients, with good clinical outcomes. CONCLUSIONS: The lungs of donors colonized with multidrug-resistant bacteria may be safely used when recipients receive prompt tailored antibiotic treatment.

Executive summary of the Consensus Statement of the Transplant Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the National Transplant Organization (ONT) on the Selection Criteria of Donors of Solid Organs in relation to Infectious Diseases.

The immunosuppressive treatment that recipients receive from a solid organ transplantation hinders the defensive response to infection. Its transmission from the donor can cause dysfunction or loss of the graft and even death of the recipient if proper preventive measures are not established. This potential risk should be thoroughly evaluated to minimise the risk of infection transmission from donor to recipient, especially with organ transplantation from donors with infections, without increasing graft dysfunction and morbidity and mortality in the recipient. This document aims to review current knowledge about infection screening in potential donors and offer clinical and microbiological recommendations about the use of organs from donors with infection based on available scientific evidence.

Phaeohyphomycosis caused by Medicopsis romeroi in solid organ transplant recipients: Report of two cases and comprehensive review of the literature.

Medicopsis romeroi is a melanized coelomycetous fungus, mainly found in tropical and subtropical regions and an uncommon cause of infection in solid organ transplant (SOT) recipients. We describe two cases of SOT recipients diagnosed with phaeohyphomycosis due to M romeroi and provide a comprehensive literature review. These infections should be considered in patients native to tropical countries with a localized skin and soft tissue infection. Sequencing is needed for accurate identification of uncommon melanized fungi. Surgical treatment is recommended to cure the infection and co-adjunctive oral antifungals should be considered.

Safety and effectiveness of sodium colistimethate-loaded nanostructured lipid carriers (SCM-NLC) against P. aeruginosa: in vitro and in vivo studies following pulmonary and intramuscular administration.

The usefulness of nanotechnology to increase the bioavailability of drugs and decrease their toxicity may be a tool to deal with multiresistant P. aeruginosa (Mr-Pa) respiratory infections. We describe the preparation and the in vivo efficacy and safety of sodium colistimethate-loaded nanostructured lipid carriers (SCM-NLC) by the pulmonary and intramuscular routes. Nanoparticles showed 1-2 mg/L minimum inhibitory concentration against eight extensively drug-resistant P. aeruginosa strains. In vivo, SCM-NLC displayed significantly lower CFU/g lung than the saline and similar to that of the free SCM, even the dose in SCM-NLC group was lower than free SCM. There was no tissue damage related to the treatments. Biodistribution assessments showed a mild systemic absorption after nebulization and a notorious absorption after IM route. Altogether, it could be concluded that SCM-NLC were effective against P. aeruginosa in vivo, not toxic and distribute efficiently to the lung and liver after pulmonary or intramuscular administrations.

Sterilization Procedure for Temperature-Sensitive Hydrogels Loaded with Silver Nanoparticles for Clinical Applications.

Hydrogels (HG) have recognized benefits as drug delivery platforms for biomedical applications. Their high sensitivity to sterilization processes is however one of the greatest challenges regarding their clinical translation. Concerning infection diseases, prevention of post-operatory related infections is crucial to ensure appropriate patient recovery and good clinical outcomes. Silver nanoparticles (AgNPs) have shown good antimicrobial properties but sustained release at the right place is required. Thus, we produced and characterized thermo-sensitive HG based on Pluronic® F127 loaded with AgNPs (HG-AgNPs) and their integrity and functionality after sterilization by dry-heat and autoclave methods were carefully assessed. The quality attributes of HG-AgNPs were seriously affected by dry-heat methods but not by autoclaving methods, which allowed to ensure the required sterility. Also, direct sterilization of the final HG-AgNPs product proved more effective than of the raw material, allowing simpler production procedures in non-sterile conditions. The mechanical properties were assessed in post mortem rat models and the HG-AgNPs were tested for its antimicrobial properties in vitro using extremely drug-resistant (XDR) clinical strains. The produced HG-AgNPs prove to be versatile, easy produced and cost-effective products, with activity against XDR strains and an adequate gelation time and spreadability features and optimal for in situ biomedical applications.

Efficacy of liposomal amphotericin B and anidulafungin using an antifungal lock technique (ALT) for catheter-related Candida albicans and Candida glabrata infections in an experimental model.

OBJECTIVE: The aims of this study were as follows. First, we sought to compare the in vitro susceptibility of liposomal amphotericin B (LAmB) and anidulafungin on Candida albicans and Candida glabrata biofilms growing on silicone discs. Second, we sought to compare the activity of LAmB versus anidulafungin for the treatment of experimental catheter-related C. albicans and C. glabrata infections with the antifungal lock technique in a rabbit model. METHODS: Two C. albicans and two C. glabrata clinical strains were used. The minimum biofilm eradication concentration for 90% eradication (MBEC90) values were determined after 48h of treatment with LAmB and anidulafungin. Confocal microscopy was used to visualize the morphology and viability of yeasts growing in biofilms. Central venous catheters were inserted into New Zealand rabbits, which were inoculated of each strain of C. albicans and C. glabrata. Then, catheters were treated for 48h with saline or with antifungal lock technique using either LAmB (5mg/mL) or anidulafungin (3.33mg/mL). RESULTS: In vitro: anidulafungin showed greater activity than LAmB against C. albicans and C. glabrata strains. For C. albicans: MBEC90 of anidulafungin versus LAmB: CA176, 0.03 vs. 128 mg/L; CA180, 0.5 vs. 64 mg/L. For C. glabrata: MBEC90 of anidulafungin versus LAmB: CG171, 0.5 vs. 64 mg/L; CG334, 2 vs. 32 mg/L. In vivo: for C. albicans species, LAmB and anidulafungin achieved significant reductions relative to growth control of log10 cfu recovered from the catheter tips (CA176: 3.6±0.3 log10 CFU, p≤0.0001; CA180: 3.8±0.1 log10 CFU, p≤0.01). For C. glabrata, anidulafungin lock therapy achieved significant reductions relative to the other treatments (CG171: 4.8 log10 CFU, p≤0.0001; CG334: 5.1 log10 CFU, p≤0.0001). CONCLUSIONS: For the C. albicans strains, both LAmB and anidulafungin may be promising antifungal lock technique for long-term catheter-related infections; however, anidulafungin showed significantly higher activity than LAmB against the C. glabrata strains.

Executive summary of clinical practice guideline for the management of invasive diseases caused by Aspergillus: 2018 Update by the GEMICOMED-SEIMC/REIPI.

Aspergillus infection is a significant cause of morbi-mortality in an at-risk population. The Study Group of Fungal Infections (GEMICOMED) from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has reviewed announcements made in invasive aspergillosis management. We have organized our recommendations in such a way as to provide a guide in resolving different clinical situations concerning the entire spectrum of invasive diseases caused by Aspergillus in various populations. Diagnostic approach, treatment and preventions strategies are outlined. It is not our aim that these guidelines supplant clinical judgment with respect to specific patients; however, it is our objective to perform a comprehensive summary of quality of care evidence for invasive aspergillosis management in different settings.

Is antibody-mediated rejection in kidney transplant recipients a risk factor for developing cytomegalovirus or BK virus infection? Results from a case-control study.

BACKGROUND: Data are scarce on cytomegalovirus (CMV) and BK virus (BKV) infection after antibody-mediated rejection (ABMR). OBJECTIVES: We hypothesized that the immunological response in patients with ABMR or the immune modulation associated with its treatment could predispose to CMV and BKV infection. Our objective was to investigate this hypothesis. STUDY DESIGN: We conducted a single-center, matched case-control study (1:2 ratio) to analyze CMV and BKV replication during the first year after the ABMR diagnosis in kidney transplant recipients. Adult recipients with a histopathological diagnosis of ABMR between 2007-2015 were included as cases. Controls were kidney recipients who underwent transplantation immediately before and after the index case. RESULTS: Fifty-eight patients diagnosed with ABMR (33 chronic active ABMR and 25 acute ABMR), with their matched controls (116) were included. Forty-four cases received treatment for ABMR, including plasmapheresis (41), immunoglobulins (40), and rituximab (31). Within 1 year after ABMR, cases showed CMV replication more often than controls (9/58, 15.5% vs 7/116, 6%, OR = 4.21, CI 1.10-16.16, p = 0.04). Over the study period, CMV PCR determinations were requested more frequently in cases than controls (46/58, 79.3% vs 63/116, 54.3%, OR = 4.58, CI 1.92-10.9, p = 0.001). On multivariate analysis adjusted for CMV PCR determinations, retransplantation, antithymocyte globulin treatment and methylprednisolone treatment for acute rejection, CMV replication remained more common in cases than in controls (OR = 2.41, CI 0.49-11.73, p = 0.28). There were no differences in BKV replication in either urine or blood. CONCLUSIONS: ABMR may be a risk factor for CMV but not for BKV replication in kidney transplant recipients.