European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2018
A high percentage of venous lines (VLs) are placed in non-ICU patients, particularly those treate... more A high percentage of venous lines (VLs) are placed in non-ICU patients, particularly those treated in the internal medicine department (IMD). We assessed adherence to VL care after a training program aimed at nurses and clinicians attending patients admitted to Spanish IMDs. We performed a multicenter prospective observational point prevalence study in 14 Spanish IMDs in 2013 and 2016. We included all adult patients (> 18 years) admitted to IMDs on the study day and reviewed nursing records for patients with VL in place before and after a 1-year training program during 2015. Answers from an interview with head nurses of the IMDs regarding commonly used practices in the daily management of VLs were also compared. A total of 638 and 693 patients were seen during each period, respectively, and 530 and 598 patients had ≥ 1 VL implanted (83.1 vs. 86.3%). Catheters were considered unnecessary in 12.8 and 15.0% of cases (p = 0.28). Daily recording of the need for catheter use increased ...
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2018
The Architect HIV Ag/Ab Combo Assay, a fourth-generation ELISA, has proven to be highly reliable ... more The Architect HIV Ag/Ab Combo Assay, a fourth-generation ELISA, has proven to be highly reliable for the diagnosis of HIV infection. However, its high sensitivity may lead to false-positive results. To evaluate the diagnostic performance of Architect in a low-prevalence population and to assess the role of the sample-to-cutoff ratio (S/CO) in reducing the frequency of false-positive results. We conducted a retrospective study of samples analyzed by Architect between January 2015 and June 2017. Positive samples were confirmed by immunoblot (RIBA) or nucleic acid amplification tests (NAATs). Different S/CO thresholds (1, 2.5, 10, 25, and 100) were analyzed to determine sensitivity, specificity, and negative and positive predictive values (NPV, PPV). ROC analysis was used to determine the optimal S/CO. A total of 69,471 samples were analyzed. 709 (1.02%) were positive by Architect. Of these, 63 (8.89%) were false-positive results. Most of them (93.65%) were in samples with S/CO < 10...
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, Jan 28, 2018
The question of whether to obtain 2 or 3 sets of blood cultures to assess the etiology of bloodst... more The question of whether to obtain 2 or 3 sets of blood cultures to assess the etiology of bloodstream infections (BSIs) remains open to debate. Few studies have assessed the proportion of BSIs missed without the third blood culture set (BCS). The aim of our study was to determine the proportion of BSIs that would be missed without the third BCS in a hospital where obtaining 3 BCSs is the standard of care. We performed a descriptive retrospective study in Hospital Gregorio Marañón (Madrid) from 2010 to 2013. We included all episodes of BSI in which 3 BCSs were systematically obtained. We included 4,000 episodes of BSI between 2010 and 2013. Without the third BCS, we would have missed 298 (7.5%) episodes of BSI: 141 (47.3%) by gram-positive microorganisms, 147 (49.3%) by gram-negative microorganisms, and 10 (3.4%) by yeasts. In 132/298 (44.3%) of the episodes another clinical sample have been obtained within a week of the BCS extraction; in 101/298 (33.9%), the same microorganism was ...
Tedizolid is a second-generation oxazolidinone with activity against Gram-positive bacteria, incl... more Tedizolid is a second-generation oxazolidinone with activity against Gram-positive bacteria, including MRSA isolates resistant to linezolid. Pivotal clinical trials showed that tedizolid at 200 mg once-daily for 6 days is not inferior to linezolid 600 mg twice daily for 10 days in patients with SSTI. The comparison of adverse events is favorable to tedizolid under the circumstances of the clinical trials. This is a review of recent literature on tedizolid, its use in special populations and potential adverse effects. Findings suggest that tedizolid can be used in SSTI in adolescents, those older than 65 years, obese individuals and patients with diabetic foot infections. Forthcoming research to determine the future uses of this drug in other clinical syndromes requires demonstration of tolerance whenever tedizolid is administered for longer than 6 days.We also speculate on missing data and potential future indications of tedizolid in the highly competitive field of the treatment of ...
The Journal of thoracic and cardiovascular surgery, Jan 12, 2018
The incidence density of ventilator-associated pneumonia (VAP) is higher in patients undergoing m... more The incidence density of ventilator-associated pneumonia (VAP) is higher in patients undergoing major heart surgery than in other populations, despite the introduction of bundles of preventive measures, because many risk factors are not amenable to intervention. Selective digestive decontamination (SDD) has been shown to be efficacious for decreasing the frequency of VAP, although it has not been incorporated into the routine of most intensive care units. The objective of our study was to evaluate the efficacy of SDD without parenteral antibiotics for preventing VAP in a major heart surgery intensive care unit. We compared the incidence of VAP before the introduction of SDD (17 months) and during the 17 months after the introduction of SDD and examined its ecologic influence. The rates of VAP in the overall population before and during the intervention were 16.26/1000 days and 6.80 episodes/1000 days of mechanical ventilation, respectively (P = .01). The rates of VAP in the 173 pati...
The presence of clusters in units with a high incidence of candidemia suggests the need for preve... more The presence of clusters in units with a high incidence of candidemia suggests the need for prevention of candidemia. We analyzed the percentage of patients involved in clusters and its evolution over a large period of time in a tertiary hospital.We studied 432 patients admitted to Gregorio Marañón Hospital with candidemia caused by (n=276) or (n=156) between January 2007 and December 2014. Incident isolates were genotyped. A cluster was defined as a group of ≥2 patients infected by an identical genotype; we considered clusters to be "tracking clusters" when the patients involved in the cluster were admitted to the same ward within a period of 24 months. Study period was split into two periods: 2007-2010 (Period 1) and 2011-2014 (Period 2).The number of episodes of and candidemia (n=262 vs. n=170), the mean incidence (1.62 vs. 1.36 episodes per 1,000 admissions), and the percentage of episodes caused by clusters (overall clusters [lsqb]40% vs. 12%[rsqb] and tracking cluste...
The new lipoglycopeptide dalbavancin has only been approved for acute bacterial skin and skin str... more The new lipoglycopeptide dalbavancin has only been approved for acute bacterial skin and skin structure infections. However, its alternative use as a catheter lock solution could facilitate the conservative management of catheter-related bloodstream infection. Our objective was to assess the stability and activity of dalbavancin alone and in combination with heparin against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) biofilms. We also compared the results with those obtained with vancomycin alone and in combination with heparin. We used a 96-well plate in vitro model based on 24 h biofilms of MRSA and MRSE (ATCC 43300, ATCC 35984 and one clinical strain of each). The biofilms were exposed to dalbavancin (0.128 mg ml) and vancomycin (5 mg ml) alone and in combination with heparin (60 IU). The median percentage reductions in metabolic activity, biomass, bacterial load, and cell viability for each solution were compared...
Transplant infectious disease : an official journal of the Transplantation Society, Jan 30, 2018
Berlin Heart EXCOR devices (BHED) are ventricular assist devices (VAD) used mainly as a bridge to... more Berlin Heart EXCOR devices (BHED) are ventricular assist devices (VAD) used mainly as a bridge to heart transplantation (HT) in pediatric population. The aim of our study is to report the infections diagnosed in adult patients undergoing a BHED implantation. Adult patients receiving a BHED between Jul 2009 and Oct 2017 at our institution were included. Infections were classified according to the International Society of Heart and Lung Transplantation definitions in VAD-Specific (VAD-S), VAD-Related (VAD-R) and non-VAD (N-VAD). Fifteen patients underwent BHED implantation, which was maintained for a mean of 92 (19-195) days. Infection occurred in 13 patients who developed 36 infectious episodes: 5 VAD-S (5 cannula infections); 8 VAD-R (5 bloodstream infections and 3 mediastinitis) and 24 N-VAD (7 urinary tract infections, 6 Cytomegalovirus diseases and others). Overall, 27 (75%) were bacterial, 7 (19.4%) were viral and there was one (2.7%) fungal infection. Eleven patients underwent ...
We studied the ability of five echinocandin-susceptible C. glabrata isolates to acquire in vitro ... more We studied the ability of five echinocandin-susceptible C. glabrata isolates to acquire in vitro resistance to anidulafungin and micafungin. All isolates became phenotypically resistant after 2-4 days of exposure to low and constant micafungin concentrations (P < .05). Mutations in the HS1 region of the FKS2 gene were found in all isolates. The acquisition of resistance was not related to the previous use of antifungal treatment in the patients or the presence of mutations at MSH2 gene. We found differences (P < .0001) in the median survival of Galleria mellonella larvae infected with FKS2 mutant isolates (5 days) and wild-type isolates (3 days).
We report the mutant prevention concentration (MPC) and mutant selection window (MSW) for micafun... more We report the mutant prevention concentration (MPC) and mutant selection window (MSW) for micafungin and anidulafungin administered to treat We also determine the mutation frequency. We studied 20 echinocandin-susceptible, fluconazole-intermediate, and wild-type isolates. Adjusted inocula were stroked directly onto Sabouraud agar plates containing different concentrations of micafungin or anidulafungin and visually inspected daily for up to 5 days of incubation. Individual colonies growing on the plates containing echinocandins at 1 mg/liter were selected for antifungal susceptibility testing. The genes of the resulting individual phenotypically resistant colonies were sequenced, and the MPC, MSW, and mutation frequency were determined. Biofilm was quantified, and the growth kinetics and virulence ( model) of the resulting individual mutant colonies were studied. For micafungin and anidulafungin, we found similar results for the MPC (0.06 to 2 mg/liter and 0.25 to 2 mg/liter, respec...
Antimicrobial agents and chemotherapy, Jan 30, 2018
We examined the rapid evaluation of susceptibility to echinocandins in spp. using the Etest perfo... more We examined the rapid evaluation of susceptibility to echinocandins in spp. using the Etest performed directly on positive blood cultures and anidulafungin-containing agar plates. We prospectively collected 80 positive blood cultures (Bactec™-FX system, Becton-Dickinson, Cockeysville, Maryland, USA) with echinocandin-susceptible spp (n=60) and echinocandin-intermediate (n=20) from patients with candidemia. Additionally, blood culture bottles of nonfungemic/bacteremic patients were spiked with 35 echinocandin-resistant spp. isolates. A total of 2-4 drops of medium from each bottle was stroked directly both onto RPMI 1640 agar plates with micafungin and anidulafungin Etest strips (ET) and on Sabouraud agar plates containing 2 mg/L of anidulafungin. Isolates were tested according to the EUCAST method and Etest standard (ET). Essential and categorical agreement between methods was calculated. Essential agreement and categorical agreement between EUCAST and ET and ET were both >97.4%....
We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG... more We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy. Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome). Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA [3/14 (21.4%) versus 8/35 (22.9%), P = 1] and BDG [8/14...
Diagnosis of complicated candidaemia represents a challenge for clinicians since early clinical m... more Diagnosis of complicated candidaemia represents a challenge for clinicians since early clinical manifestations may be non-specific and difficult to identify, thus precluding an appropriate treatment. This was a multicentre prospective study for predicting complicated episodes in patients with bloodstream infection caused by Candida species, while assessing the value of follow-up blood cultures (BCs) and the persistence of positive results for T2Candida MR (T2MR) and blood β-d-glucan (BDG) tests. Immediately after the first positive BC yielding Candida species, samples were obtained on days 0, +2, +4, +7 and +14, to simultaneously perform follow-up BC, T2MR and BDG. An episode of candidaemia was defined as 'complicated' when (i) it caused septic metastasis; and/or (ii) it was the cause of the patient's death. From January to June 2017, 30 patients were enrolled in the study. Of these, nine (30%) had complicated candidaemia. Values of persistently positive samples for the ...
International journal of antimicrobial agents, Jan 24, 2017
Dalbavancin is a lipoglycopeptide with a very prolonged half-life that enables treatments with a ... more Dalbavancin is a lipoglycopeptide with a very prolonged half-life that enables treatments with a single IV administration that has been approved to treat complicated skin and soft tissue infections. Information on the efficacy and safety of Dalbavancin in other situations is very scarce. This retrospective study includes adult patients who received at least one dose of Dalbavancin between 2016 and 2017 in 29 institutions in Spain. Primary objective was to report the use of Dalbavancin in clinical practice including its efficacy and tolerability. We also tried to evaluate the potential impact of Dalbavancin on reduction of length of hospital stay and hospital costs. A total of 69 patients received Dalbavancin during the study period (58% male, median age 63.5 years). Dalbavancin was used to treat prosthetic joint infections (29.0%), acute bacterial skin and skin structure infection (21.7%), osteomyelitis (17.4%) and catheter-related bacteraemia (11.6%). These infections were mainly c...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 23, 2017
Patients with cirrhosis are at high risk of Clostridium difficile infection (CDI). Rifaximin is c... more Patients with cirrhosis are at high risk of Clostridium difficile infection (CDI). Rifaximin is commonly used in cirrhotic patients as prophylaxis for hepatic encephalopathy (HE). Several studies have demonstrated the efficacy of rifaximin in the treatment of CDI; however, resistance to rifaximin has also been reported. Few studies have assessed the risk of developing CDI in cirrhotic patients receiving rifaximin. Our objective was to assess the incidence and characteristics of CDI in cirrhotic patients, especially in those who received rifaximin. We assessed the incidence and clinical characteristics of CDI in cirrhotic patients over a 6-year period in our hospital. Medical charts were retrospectively reviewed. Ribotyping and antimicrobial susceptibility testing of all strains against rifaximin was performed. A total of 388 cirrhotic patients were included, of whom 127 patients had at least 1 episode of diarrhea in which a sample was sent to the laboratory. CDI was detected in 46 p...
Candidemia acquired outside critical care or hematological areas has received much attention in r... more Candidemia acquired outside critical care or hematological areas has received much attention in recent years; however, data on candidemia in surgical departments are very scarce. Our objectives were to describe episodes of candidemia diagnosed in surgical wards and to compare them with episodes occurring in medical wards. We performed a post hoc analysis of a prospective, multicenter study implemented in Spain during 2010-2011 (CANDIPOP project). Of the 752 episodes of candidemia, 369 (49.1%) occurred in patients admitted to surgical wards (165, 21.9%) or medical wards (204, 27.2%). Clinical characteristics associated with surgical patients were solid tumor as underlying disease, recent surgery, indwelling CVC, and parenteral nutrition. Candidemia was more commonly related to a CVC in the surgical than in the medical wards. The CVC was removed more frequently and early management was more appropriate within 48 hours of blood sampling in the surgical patients. Overall, 30-day mortali...
The purpose of this study was to determine among patients with candidemia the real rate of ophtha... more The purpose of this study was to determine among patients with candidemia the real rate of ophthalmoscopy and the impact of performing ocular assessment on the outcome of the disease. We performed a post hoc analysis of a prospective, multicenter, population-based candidemia surveillance program implemented in Spain during 2010-2011 (CANDIPOP). Ophthalmoscopy was performed in only 168 of the 365 patients with candidemia (46%). Ocular lesions related to candidemia were found in only 13/168 patients (7.7%), of whom 1 reported ocular symptoms (incidence of symptomatic disease in the whole population, 0.27% [1/365]). Ophthalmological findings led to a change in antifungal therapy in only 5.9% of cases (10/168), and performance of the test was not related to a better outcome. Ocular candidiasis was not associated with a worse outcome and progressed favorably in all but 1 evaluable patient, who did not experience vision loss. The low frequency of ophthalmoscopy and ocular involvement and ...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 25, 2017
Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with intern... more Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations consisting in the combination of surgery and subsequent azole treatment. PVE-C collected in Spain and France between 2001 and 2015 were retrospectively analyzed with a focus on management and outcome. Forty-six cases were followed up for a median of 9 months. Twenty-two (48%) patients had a past history of endocarditis; 30 (65%) cases were nosocomial or healthcare-related, 9 (20%) patients were intravenous drug users. "Induction" therapy mainly consisted in a liposomal amphotericin B-based (n=21) or an echinocandin-based therapy (n=13). Overall, 19 (41%) patients were operated. Patients less than 66 years old and without cardiac failure more likely underwent cardiac surgery (aOR [95% IC] = 6.80 [1.59-29.13]) and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival at 6 months. Patients who receive...
We studied 19 cases of proven/probable mucormycosis diagnosed from 2007 to 2015 in our hospital a... more We studied 19 cases of proven/probable mucormycosis diagnosed from 2007 to 2015 in our hospital and assessed the microbiological characteristics of the isolates. We recorded the incidence of mucormycosis and clinical and microbiological data of infected patients. Isolates were identified to molecular level and tested for their antifungal susceptibility to azoles, amphotericin B, and liposomal amphotericin B according to the CLSI M-38 A2 procedure. The incidence of mucormycosis in cases/100,000 hospital admissions during 2007-2015 increased significantly with respect to that reported in 1988-2006 (3.3 vs. 1.2; P<0.05). Patients mainly had hematological malignancies (52.6%) and/or trauma/surgical wounds (52.6%) and had received antifungal agents before the diagnosis of mucormycosis in 68% of cases. Diagnosis was by isolation (n = 17/19) and/or direct staining (n = 17/18) of Mucorales fungi in clinical samples. Identification was by panfungal PCR in patients with negative results in...
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2018
A high percentage of venous lines (VLs) are placed in non-ICU patients, particularly those treate... more A high percentage of venous lines (VLs) are placed in non-ICU patients, particularly those treated in the internal medicine department (IMD). We assessed adherence to VL care after a training program aimed at nurses and clinicians attending patients admitted to Spanish IMDs. We performed a multicenter prospective observational point prevalence study in 14 Spanish IMDs in 2013 and 2016. We included all adult patients (> 18 years) admitted to IMDs on the study day and reviewed nursing records for patients with VL in place before and after a 1-year training program during 2015. Answers from an interview with head nurses of the IMDs regarding commonly used practices in the daily management of VLs were also compared. A total of 638 and 693 patients were seen during each period, respectively, and 530 and 598 patients had ≥ 1 VL implanted (83.1 vs. 86.3%). Catheters were considered unnecessary in 12.8 and 15.0% of cases (p = 0.28). Daily recording of the need for catheter use increased ...
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2018
The Architect HIV Ag/Ab Combo Assay, a fourth-generation ELISA, has proven to be highly reliable ... more The Architect HIV Ag/Ab Combo Assay, a fourth-generation ELISA, has proven to be highly reliable for the diagnosis of HIV infection. However, its high sensitivity may lead to false-positive results. To evaluate the diagnostic performance of Architect in a low-prevalence population and to assess the role of the sample-to-cutoff ratio (S/CO) in reducing the frequency of false-positive results. We conducted a retrospective study of samples analyzed by Architect between January 2015 and June 2017. Positive samples were confirmed by immunoblot (RIBA) or nucleic acid amplification tests (NAATs). Different S/CO thresholds (1, 2.5, 10, 25, and 100) were analyzed to determine sensitivity, specificity, and negative and positive predictive values (NPV, PPV). ROC analysis was used to determine the optimal S/CO. A total of 69,471 samples were analyzed. 709 (1.02%) were positive by Architect. Of these, 63 (8.89%) were false-positive results. Most of them (93.65%) were in samples with S/CO < 10...
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, Jan 28, 2018
The question of whether to obtain 2 or 3 sets of blood cultures to assess the etiology of bloodst... more The question of whether to obtain 2 or 3 sets of blood cultures to assess the etiology of bloodstream infections (BSIs) remains open to debate. Few studies have assessed the proportion of BSIs missed without the third blood culture set (BCS). The aim of our study was to determine the proportion of BSIs that would be missed without the third BCS in a hospital where obtaining 3 BCSs is the standard of care. We performed a descriptive retrospective study in Hospital Gregorio Marañón (Madrid) from 2010 to 2013. We included all episodes of BSI in which 3 BCSs were systematically obtained. We included 4,000 episodes of BSI between 2010 and 2013. Without the third BCS, we would have missed 298 (7.5%) episodes of BSI: 141 (47.3%) by gram-positive microorganisms, 147 (49.3%) by gram-negative microorganisms, and 10 (3.4%) by yeasts. In 132/298 (44.3%) of the episodes another clinical sample have been obtained within a week of the BCS extraction; in 101/298 (33.9%), the same microorganism was ...
Tedizolid is a second-generation oxazolidinone with activity against Gram-positive bacteria, incl... more Tedizolid is a second-generation oxazolidinone with activity against Gram-positive bacteria, including MRSA isolates resistant to linezolid. Pivotal clinical trials showed that tedizolid at 200 mg once-daily for 6 days is not inferior to linezolid 600 mg twice daily for 10 days in patients with SSTI. The comparison of adverse events is favorable to tedizolid under the circumstances of the clinical trials. This is a review of recent literature on tedizolid, its use in special populations and potential adverse effects. Findings suggest that tedizolid can be used in SSTI in adolescents, those older than 65 years, obese individuals and patients with diabetic foot infections. Forthcoming research to determine the future uses of this drug in other clinical syndromes requires demonstration of tolerance whenever tedizolid is administered for longer than 6 days.We also speculate on missing data and potential future indications of tedizolid in the highly competitive field of the treatment of ...
The Journal of thoracic and cardiovascular surgery, Jan 12, 2018
The incidence density of ventilator-associated pneumonia (VAP) is higher in patients undergoing m... more The incidence density of ventilator-associated pneumonia (VAP) is higher in patients undergoing major heart surgery than in other populations, despite the introduction of bundles of preventive measures, because many risk factors are not amenable to intervention. Selective digestive decontamination (SDD) has been shown to be efficacious for decreasing the frequency of VAP, although it has not been incorporated into the routine of most intensive care units. The objective of our study was to evaluate the efficacy of SDD without parenteral antibiotics for preventing VAP in a major heart surgery intensive care unit. We compared the incidence of VAP before the introduction of SDD (17 months) and during the 17 months after the introduction of SDD and examined its ecologic influence. The rates of VAP in the overall population before and during the intervention were 16.26/1000 days and 6.80 episodes/1000 days of mechanical ventilation, respectively (P = .01). The rates of VAP in the 173 pati...
The presence of clusters in units with a high incidence of candidemia suggests the need for preve... more The presence of clusters in units with a high incidence of candidemia suggests the need for prevention of candidemia. We analyzed the percentage of patients involved in clusters and its evolution over a large period of time in a tertiary hospital.We studied 432 patients admitted to Gregorio Marañón Hospital with candidemia caused by (n=276) or (n=156) between January 2007 and December 2014. Incident isolates were genotyped. A cluster was defined as a group of ≥2 patients infected by an identical genotype; we considered clusters to be "tracking clusters" when the patients involved in the cluster were admitted to the same ward within a period of 24 months. Study period was split into two periods: 2007-2010 (Period 1) and 2011-2014 (Period 2).The number of episodes of and candidemia (n=262 vs. n=170), the mean incidence (1.62 vs. 1.36 episodes per 1,000 admissions), and the percentage of episodes caused by clusters (overall clusters [lsqb]40% vs. 12%[rsqb] and tracking cluste...
The new lipoglycopeptide dalbavancin has only been approved for acute bacterial skin and skin str... more The new lipoglycopeptide dalbavancin has only been approved for acute bacterial skin and skin structure infections. However, its alternative use as a catheter lock solution could facilitate the conservative management of catheter-related bloodstream infection. Our objective was to assess the stability and activity of dalbavancin alone and in combination with heparin against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) biofilms. We also compared the results with those obtained with vancomycin alone and in combination with heparin. We used a 96-well plate in vitro model based on 24 h biofilms of MRSA and MRSE (ATCC 43300, ATCC 35984 and one clinical strain of each). The biofilms were exposed to dalbavancin (0.128 mg ml) and vancomycin (5 mg ml) alone and in combination with heparin (60 IU). The median percentage reductions in metabolic activity, biomass, bacterial load, and cell viability for each solution were compared...
Transplant infectious disease : an official journal of the Transplantation Society, Jan 30, 2018
Berlin Heart EXCOR devices (BHED) are ventricular assist devices (VAD) used mainly as a bridge to... more Berlin Heart EXCOR devices (BHED) are ventricular assist devices (VAD) used mainly as a bridge to heart transplantation (HT) in pediatric population. The aim of our study is to report the infections diagnosed in adult patients undergoing a BHED implantation. Adult patients receiving a BHED between Jul 2009 and Oct 2017 at our institution were included. Infections were classified according to the International Society of Heart and Lung Transplantation definitions in VAD-Specific (VAD-S), VAD-Related (VAD-R) and non-VAD (N-VAD). Fifteen patients underwent BHED implantation, which was maintained for a mean of 92 (19-195) days. Infection occurred in 13 patients who developed 36 infectious episodes: 5 VAD-S (5 cannula infections); 8 VAD-R (5 bloodstream infections and 3 mediastinitis) and 24 N-VAD (7 urinary tract infections, 6 Cytomegalovirus diseases and others). Overall, 27 (75%) were bacterial, 7 (19.4%) were viral and there was one (2.7%) fungal infection. Eleven patients underwent ...
We studied the ability of five echinocandin-susceptible C. glabrata isolates to acquire in vitro ... more We studied the ability of five echinocandin-susceptible C. glabrata isolates to acquire in vitro resistance to anidulafungin and micafungin. All isolates became phenotypically resistant after 2-4 days of exposure to low and constant micafungin concentrations (P < .05). Mutations in the HS1 region of the FKS2 gene were found in all isolates. The acquisition of resistance was not related to the previous use of antifungal treatment in the patients or the presence of mutations at MSH2 gene. We found differences (P < .0001) in the median survival of Galleria mellonella larvae infected with FKS2 mutant isolates (5 days) and wild-type isolates (3 days).
We report the mutant prevention concentration (MPC) and mutant selection window (MSW) for micafun... more We report the mutant prevention concentration (MPC) and mutant selection window (MSW) for micafungin and anidulafungin administered to treat We also determine the mutation frequency. We studied 20 echinocandin-susceptible, fluconazole-intermediate, and wild-type isolates. Adjusted inocula were stroked directly onto Sabouraud agar plates containing different concentrations of micafungin or anidulafungin and visually inspected daily for up to 5 days of incubation. Individual colonies growing on the plates containing echinocandins at 1 mg/liter were selected for antifungal susceptibility testing. The genes of the resulting individual phenotypically resistant colonies were sequenced, and the MPC, MSW, and mutation frequency were determined. Biofilm was quantified, and the growth kinetics and virulence ( model) of the resulting individual mutant colonies were studied. For micafungin and anidulafungin, we found similar results for the MPC (0.06 to 2 mg/liter and 0.25 to 2 mg/liter, respec...
Antimicrobial agents and chemotherapy, Jan 30, 2018
We examined the rapid evaluation of susceptibility to echinocandins in spp. using the Etest perfo... more We examined the rapid evaluation of susceptibility to echinocandins in spp. using the Etest performed directly on positive blood cultures and anidulafungin-containing agar plates. We prospectively collected 80 positive blood cultures (Bactec™-FX system, Becton-Dickinson, Cockeysville, Maryland, USA) with echinocandin-susceptible spp (n=60) and echinocandin-intermediate (n=20) from patients with candidemia. Additionally, blood culture bottles of nonfungemic/bacteremic patients were spiked with 35 echinocandin-resistant spp. isolates. A total of 2-4 drops of medium from each bottle was stroked directly both onto RPMI 1640 agar plates with micafungin and anidulafungin Etest strips (ET) and on Sabouraud agar plates containing 2 mg/L of anidulafungin. Isolates were tested according to the EUCAST method and Etest standard (ET). Essential and categorical agreement between methods was calculated. Essential agreement and categorical agreement between EUCAST and ET and ET were both >97.4%....
We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG... more We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy. Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome). Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA [3/14 (21.4%) versus 8/35 (22.9%), P = 1] and BDG [8/14...
Diagnosis of complicated candidaemia represents a challenge for clinicians since early clinical m... more Diagnosis of complicated candidaemia represents a challenge for clinicians since early clinical manifestations may be non-specific and difficult to identify, thus precluding an appropriate treatment. This was a multicentre prospective study for predicting complicated episodes in patients with bloodstream infection caused by Candida species, while assessing the value of follow-up blood cultures (BCs) and the persistence of positive results for T2Candida MR (T2MR) and blood β-d-glucan (BDG) tests. Immediately after the first positive BC yielding Candida species, samples were obtained on days 0, +2, +4, +7 and +14, to simultaneously perform follow-up BC, T2MR and BDG. An episode of candidaemia was defined as 'complicated' when (i) it caused septic metastasis; and/or (ii) it was the cause of the patient's death. From January to June 2017, 30 patients were enrolled in the study. Of these, nine (30%) had complicated candidaemia. Values of persistently positive samples for the ...
International journal of antimicrobial agents, Jan 24, 2017
Dalbavancin is a lipoglycopeptide with a very prolonged half-life that enables treatments with a ... more Dalbavancin is a lipoglycopeptide with a very prolonged half-life that enables treatments with a single IV administration that has been approved to treat complicated skin and soft tissue infections. Information on the efficacy and safety of Dalbavancin in other situations is very scarce. This retrospective study includes adult patients who received at least one dose of Dalbavancin between 2016 and 2017 in 29 institutions in Spain. Primary objective was to report the use of Dalbavancin in clinical practice including its efficacy and tolerability. We also tried to evaluate the potential impact of Dalbavancin on reduction of length of hospital stay and hospital costs. A total of 69 patients received Dalbavancin during the study period (58% male, median age 63.5 years). Dalbavancin was used to treat prosthetic joint infections (29.0%), acute bacterial skin and skin structure infection (21.7%), osteomyelitis (17.4%) and catheter-related bacteraemia (11.6%). These infections were mainly c...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 23, 2017
Patients with cirrhosis are at high risk of Clostridium difficile infection (CDI). Rifaximin is c... more Patients with cirrhosis are at high risk of Clostridium difficile infection (CDI). Rifaximin is commonly used in cirrhotic patients as prophylaxis for hepatic encephalopathy (HE). Several studies have demonstrated the efficacy of rifaximin in the treatment of CDI; however, resistance to rifaximin has also been reported. Few studies have assessed the risk of developing CDI in cirrhotic patients receiving rifaximin. Our objective was to assess the incidence and characteristics of CDI in cirrhotic patients, especially in those who received rifaximin. We assessed the incidence and clinical characteristics of CDI in cirrhotic patients over a 6-year period in our hospital. Medical charts were retrospectively reviewed. Ribotyping and antimicrobial susceptibility testing of all strains against rifaximin was performed. A total of 388 cirrhotic patients were included, of whom 127 patients had at least 1 episode of diarrhea in which a sample was sent to the laboratory. CDI was detected in 46 p...
Candidemia acquired outside critical care or hematological areas has received much attention in r... more Candidemia acquired outside critical care or hematological areas has received much attention in recent years; however, data on candidemia in surgical departments are very scarce. Our objectives were to describe episodes of candidemia diagnosed in surgical wards and to compare them with episodes occurring in medical wards. We performed a post hoc analysis of a prospective, multicenter study implemented in Spain during 2010-2011 (CANDIPOP project). Of the 752 episodes of candidemia, 369 (49.1%) occurred in patients admitted to surgical wards (165, 21.9%) or medical wards (204, 27.2%). Clinical characteristics associated with surgical patients were solid tumor as underlying disease, recent surgery, indwelling CVC, and parenteral nutrition. Candidemia was more commonly related to a CVC in the surgical than in the medical wards. The CVC was removed more frequently and early management was more appropriate within 48 hours of blood sampling in the surgical patients. Overall, 30-day mortali...
The purpose of this study was to determine among patients with candidemia the real rate of ophtha... more The purpose of this study was to determine among patients with candidemia the real rate of ophthalmoscopy and the impact of performing ocular assessment on the outcome of the disease. We performed a post hoc analysis of a prospective, multicenter, population-based candidemia surveillance program implemented in Spain during 2010-2011 (CANDIPOP). Ophthalmoscopy was performed in only 168 of the 365 patients with candidemia (46%). Ocular lesions related to candidemia were found in only 13/168 patients (7.7%), of whom 1 reported ocular symptoms (incidence of symptomatic disease in the whole population, 0.27% [1/365]). Ophthalmological findings led to a change in antifungal therapy in only 5.9% of cases (10/168), and performance of the test was not related to a better outcome. Ocular candidiasis was not associated with a worse outcome and progressed favorably in all but 1 evaluable patient, who did not experience vision loss. The low frequency of ophthalmoscopy and ocular involvement and ...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 25, 2017
Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with intern... more Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations consisting in the combination of surgery and subsequent azole treatment. PVE-C collected in Spain and France between 2001 and 2015 were retrospectively analyzed with a focus on management and outcome. Forty-six cases were followed up for a median of 9 months. Twenty-two (48%) patients had a past history of endocarditis; 30 (65%) cases were nosocomial or healthcare-related, 9 (20%) patients were intravenous drug users. "Induction" therapy mainly consisted in a liposomal amphotericin B-based (n=21) or an echinocandin-based therapy (n=13). Overall, 19 (41%) patients were operated. Patients less than 66 years old and without cardiac failure more likely underwent cardiac surgery (aOR [95% IC] = 6.80 [1.59-29.13]) and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival at 6 months. Patients who receive...
We studied 19 cases of proven/probable mucormycosis diagnosed from 2007 to 2015 in our hospital a... more We studied 19 cases of proven/probable mucormycosis diagnosed from 2007 to 2015 in our hospital and assessed the microbiological characteristics of the isolates. We recorded the incidence of mucormycosis and clinical and microbiological data of infected patients. Isolates were identified to molecular level and tested for their antifungal susceptibility to azoles, amphotericin B, and liposomal amphotericin B according to the CLSI M-38 A2 procedure. The incidence of mucormycosis in cases/100,000 hospital admissions during 2007-2015 increased significantly with respect to that reported in 1988-2006 (3.3 vs. 1.2; P<0.05). Patients mainly had hematological malignancies (52.6%) and/or trauma/surgical wounds (52.6%) and had received antifungal agents before the diagnosis of mucormycosis in 68% of cases. Diagnosis was by isolation (n = 17/19) and/or direct staining (n = 17/18) of Mucorales fungi in clinical samples. Identification was by panfungal PCR in patients with negative results in...
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