Humanistic burden of haemophilia A without inhibitors: A cross-sectional analysis of the HemoLIFE study.

AIM: To evaluate the impact of haemophilia A without inhibitors on humanistic outcomes in patients and caregivers. Herein, we report a cross-sectional analysis of the baseline data of persons with haemophilia (PWH) participating in the prospective study HEMOLIFE. METHODS: These data are part of a prospective, observational, and multicentre study currently being conducted in 20 hospitals in Spain by haematologists. We included subjects 12 years or older diagnosed with haemophilia. The evaluations included the Maladjustment Scale, Haemophilia-Specific Quality of Life Questionnaire for Adults (HaemoQol)/HaemoQol Short Form (Children), haemophilia-specific version of the Work Productivity and Impairment Questionnaire plus the Classroom Impairment Questionnaire (WPAI+CIQ:HS), Haemophilia Activity List (HAL)/Paediatric Haemophilia Activities List (pedHAL), visual analogue scale (VAS) for evaluating pain, Coping Pain Questionnaire-Reduced (CAD-R), and Hospital Anxiety and Depression Scale (HADS). RESULTS: A total of 81 PWH were recruited at 18 centres; 66 PWH were ≥18 years (i.e., adults), and PWH 15 were <18 years (i.e., paediatric patients). Out of the 79 evaluable subjects, 16 (20%) showed an impact of haemophilia on daily life, and the areas most affected were "leisure time" (58% showed maladjustment) and "work/studies" (47% showed maladjustment). Patients reported a higher impact of haemophilia on quality of life (mean [SD] of the transformed score) in the dimensions of "sport" (49.4 [28.6]), "physical health" (40.5 [25.8]) and "future" (37.7 [28.9]). In adults, according to HAL scores, greater impairment of function was observed in "lying/sitting/kneeling/standing," "function of legs" and "leisure activities and sports," with mean normalized scores of 64.7, 65.1 and 69.0, respectively. Productivity was mostly impacted by presenteeism. The pain was infrequent and moderate. According to the HADS scores, nine (11.5%) patients had clinical anxiety and depression. CONCLUSION: PWH without inhibitors exhibited impairments in adjustment, quality of life and functionality, especially related to leisure and sports activities, and exhibit relevant levels of anxiety and depression.

Noninterventional study assessing joint health in persons with hemophilia A after switching to turoctocog alfa pegol: design of pathfinderReal.

Background: Joint damage affects the quality of life of persons with hemophilia A. The long-term safety and efficacy of turoctocog alfa pegol (N8-GP) prophylaxis in persons with hemophilia A has been investigated in pivotal phase 3 trials in children, adolescents, and adults (pathfinder program). However, there is a lack of data on joint health in adult persons with hemophilia A treated with N8-GP. Objectives: To describe the design of the ongoing pathfinderReal study investigating the joint health status in adult persons with hemophilia A after switching to N8-GP. Methods: pathfinderReal is a multicountry, noninterventional, single-arm study (NCT05621746) of joint health in adult (≥18 years) male persons with hemophilia A who have switched to N8-GP. Patients enrolled in other interventional studies and those who have previously terminated N8-GP treatment will be excluded. Approximately 124 adults with hemophilia A will be enrolled and followed up for a maximum of 24 months. Data from routine clinical assessments of patients' joint health will be collected. The primary endpoint is change in Hemophilia Joint Health Score (defined as a change in total score of ≤2) from initiation of N8-GP treatment until the end of the study. Secondary endpoints include number of bleeding episodes, number and resolution of target joints, patient-reported outcomes of problem joint score, pain score, and change in physical function levels. An exploratory endpoint is included to measure the number of patients achieving improved Hemophilia Joint Health Score from the initiation of N8-GP until the end of the study. Conclusion: The pathfinderReal study will provide insights regarding the impact of N8-GP on joint health in persons with hemophilia A in a real-world setting.

Portal vein thrombosis in a patient with severe hemophilia B: A challenging balanced management.

Key Clinical Message: The increased life expectancy in patients with hemophilia (PwH) over the last years has raised the incidence of comorbidities, including thromboembolic events. Thromboembolic events are rare in PwH and most of them occur in the presence of exogenous risk factors. There is still scarce scientific evidence on the optimal antithrombotic treatment and management approach in this population. Abstract: In the hemophilic population thromboembolic events are rare. Most of them are often multifactorial and occur in the presence of both exogenous (orthopedic surgery, intensive replacement therapy, use of central venous catheters…) and endogenous (cardiovascular diseases) risk factors. We describe the case of a 43-year-old patient with severe hemophilia B (sHB) receiving prophylaxis with eftrenonacog alfa (rFIXFc) and antithrombotic treatment due to portal vein thrombosis. The patient was treated with extended half- life factor IX (EHL-FIX) prophylaxis maintaining higher trough levels to avoid new bleeding episodes associated to the underlying disease and the use of antithrombotic therapy with low molecular weight heparin. EHL-FIX concentrates allow prolonged intervals between intravenous infusions and higher hemostatic protection thanks to increased factor trough levels. This current case report provides clinical evidence in antithrombotic management in a patient with severe hemophilia B.

Benefits of rIX-FP prophylaxis in patients with Haemophilia B: real-world evidence from a Spanish reference centre.

Standard FIX prophylaxis for PWHB require frequent injections, which has led to the development of extended half-life products like rIX-FP (albutrepenonacog alfa) that has shown good efficacy in clinical studies. This ambispective study aims to report a real-world experience with rIX-FP in a Spanish centre with PWHB who switched from SHL-FIX or began prophylaxis with rIX-FP. Five PWHB were included in this study, Four PTP switched to rIX-FP with prophylaxis every 7 days whilst one PUP started with an every-14-days regimen. 3 PTPs extended their dosing intervals to every 14 days or every 21 days. In all PTPs, median annualized spontaneous and joint bleeding rates were maintained at 0.00 and median (range) of ABR was 0.92 (0.00-2.77) after switch to rIX-FP. Mean trough level with previous product was 3.68% (SD = 2.06), while it was 7.08% (SD = 3) with all rIX-FP dosing intervals. After switching to rIX-FP, all PTP reduced their annual infusion rate between 50 and 84% and their annual FIX consumption by 61% (59-67%). This is the first reported real-world experience with albutrepenonacog alfa in a small cohort in Spain and demonstrates good bleeding control together with a reduction of the infusion rate, factor consumption and higher through factor level than previous treatment.

VHrare study: Prevalence, clinical features and management of severe rare bleeding disorders in a large cohort.

INTRODUCTION: Rare bleeding disorders (RBD) constitute 5% of total hereditary bleeding disorders, although the number could be higher, due to the presence of undiagnosed asymptomatic patients. The objective of this study was to analyze the prevalence and characteristics of patients with severe RBDs in our area. MATERIAL AND METHODS: We analyzed the patients with RBD followed at a tertiary-level hospital between January 2014 and December 2021. RESULTS: A total of 101 patients were analyzed, with a median age at diagnosis of 27.67 years (range 0-89), of which 52.47% were male. The most frequent RBD in our population was FVII deficiency. Regarding the diagnostic reason, the most frequent cause was a preoperative test and only 14.8% reported bleeding symptoms at the time of diagnosis. A genetic study was carried out in 63.36% of patients and the most frequent mutation type found was finding a missense mutation. CONCLUSIONS: The distribution of RBDs in our centre is similar to the one reported in the literature. The majority of RBDs were diagnosed from a preoperative test and this allowed preventive treatment prior to invasive procedures to avoid bleeding complications. 83% of patients did not have a pathological bleeding phenotype according to ISTH-BAT.

von Willebrand factor neutralizing and non-neutralizing alloantibodies in 213 subjects with type 3 von Willebrand disease enrolled in 3WINTERS-IPS.

BACKGROUND: Type 3 von Willebrand disease (VWD) is the most severe form of this disease owing to the almost complete deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived products containing VWF or recombinant VWF rarely cause the development of alloantibodies against VWF that may be accompanied by anaphylactic reactions. OBJECTIVE: The objective of this study was to assess the prevalence of anti-VWF alloantibodies in subjects with type 3 VWD enrolled in the 3WINTERS-IPS. METHODS: An indirect in-house enzyme-linked immunosorbent assay has been used to test all the alloantibodies against VWF. Neutralizing antibodies (inhibitors) have been tested with a Bethesda-based method by using a VWF collagen binding (VWF:CB) assay. Samples positive for anti-VWF antibodies were further tested with Bethesda-based methods by using the semiautomated gain-of-function glycoprotein-Ib binding (VWF:GPIbM) and a VWF antigen (VWF:Ag) enzyme-linked immunosorbent assay. RESULTS: In total, 18 of the 213 (8.4%) subjects tested positive for anti-VWF antibodies and 13 of 213 (6%) had VWF:CB inhibitors. These 13 were among the 18 with anti-VWF antibodies. Of the 5 without VWF:CB inhibitors, 3 had non-neutralizing antibodies, 1 only inhibitor against VWF:GPIbM, and one could not be tested further. Ten of the 13 subjects with VWF:CB inhibitors also had VWF:GPIbM inhibitors, 6 of whom also had VWF:Ag inhibitors. Subjects with inhibitors were homozygous for VWF null alleles (11/14), homozygous for a missense variant (1/14), or partially characterized (2/14). CONCLUSIONS: Anti-VWF antibodies were found in 8.4% of subjects with type 3 VWD, whereas neutralizing VWF inhibitors were found in 6%, mainly in subjects homozygous for VWF null alleles. Because inhibitors may be directed toward different VWF epitopes, their detection is dependent on the assay used.

Activated prothrombin complex concentrate to treat bleeding events in acquired hemophilia A: BAHAS study.

OBJECTIVE: Activated prothrombin complex concentrate (aPCC) is a bypassing agent indicated to treat bleeds in patients with acquired hemophilia A (AHA). Nevertheless, its efficacy and safety in the real-world setting have not often been addressed. METHODS: We report the experience of Spanish reference centers for coagulation disorders and from acquired hemophilia Spanish Registry (AHASR) from August 2012 to February 2021. Follow-up period of 30 days after aPCC withdrawal. RESULTS: Thirty patients with a median age of 70 years old, suffering from 51 bleeds treated with aPCC were finally evaluated. As first-line treatment, aPCC stopped bleeding in 13 of 14 (92.9%) cases. aPCC as the second line after recombinant factor VIIa failure, stopped bleeding in all cases. In 17 patients, aPCC was used far from initial bleed control as prophylaxis of rebleeding with 94% effectiveness. No thromboembolic episodes were communicated. One patient developed hypofibrinogenemia, which did not prevent aPCC from halting bleeding. No other serious adverse events possibly or probably associated with aPCC were reported. CONCLUSIONS: This data support aPCC as hemostatic treatment in AHA with high effectiveness and excellent safety profile in acute bleeds and as extended use to prevent rebleedings, even in aging people with high cardiovascular risk.

Neurosurgery in a patient with severe hemophilia B: an experience using eftrenonacog alfa as perioperative management.

Extended half-life FIX (EHL-FIX) concentrates have been developed with the purpose of reducing the frequency of infusions in patients with severe or moderate hemophilia B. We describe the case of a 63-year-old patient with severe hemophilia B (sHB) treated with FIX-Fc fusion protein (rFIXFc) who underwent neurosurgery.

Clinical Efficacy and Safety of Fanhdi®, a Plasma-Derived VWF/Factor VIII Concentrate, in von Willebrand Disease in Spain: A Retrospective Study.

OBJECTIVE: To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients. METHODS: A retrospective, multicentric, observational study of VWD patients treated with Fanhdi®, a pdVWF/FVIII concentrate, from January 2011 to December 2017 was conducted at 14 centers in Spain. Efficacy and safety were evaluated for acute bleeding episodes, for prevention of bleeding in surgeries, and for secondary long-term prophylaxis. RESULTS: Seventy-two eligible patients, type 1, 2, 3 VWD (25%/38.9%/36.1%) were treated for spontaneous and traumatic bleeding (140 episodes, n = 41 patients), to prevent surgical bleeding (69 episodes, n = 43 patients); and for secondary long-term prophylaxis (18 programs, n = 13 patients). Replacement therapy with pdVWF/FVIII showed an excellent to good clinical efficacy in 96.7% of the bleeding episodes, 100% during surgical procedures and 100% during prophylaxis. No adverse events (AEs), nor serious AEs related to the product were observed. CONCLUSIONS: Fanhdi® was effective, safe and well tolerated in the management of bleeding episodes, the prevention of bleeding during surgeries, and for secondary long-term prophylaxis in VWD patients.

Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study.

BACKGROUND: Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. OBJECTIVE: To investigate whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated with bleeding severity. METHODS: European and Iranian type 3 patients were enrolled in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney test. Median differences with 95% confidence intervals (CI) were estimated using the Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using Spearman's rank correlation. RESULTS: Homozygosity/compound heterozygosity for missense variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7; P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII: C/VWF:Ag ratio was similarly increased in both. VWFpp level did not correlate with the bleeding symptoms (r = .024; P = .778). CONCLUSIONS: An increased VWFpp/VWF:Ag ratio is indicative of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense from null alleles. The VWFpp level was not associated with the severity of bleeding phenotype.

COVID-19 Infection After a Total Knee Arthroplasty in a Patient with Hemophilia A: A Case Report.

CASE: Minimal information is available regarding coronavirus disease-19 (COVID-19) patients with hemophilia A. Coagulopathy is a major pathophysiological characteristic of COVID-19; however, because of a paucity of data, it is not clear whether these patients with hemophilia are more or less prone to the severe form of the COVID-19 disease. We report the case of a hemophilic patient with confirmed COVID-19 after total knee arthroplasty. CONCLUSION: This case highlights the idea that patients with a congenital hypocoagulability stated as haemophilia may be protected against COVID-19 hypercoagulability-related adverse effects. Thromboprophylaxis with low-molecular-weight heparin should be evaluated in patients with hemophilia and COVID-19 disease.

Análisis molecular de un brote por Serratia marcescens y su posible relación con el uso de una solución de clorhexidina / Molecular analysis of an outbreak of Serratia marcescens and its possible connection with the use of a chlorhexidine solution

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Timing of DVT prophylaxis and risk of postoperative knee prosthesis infection.

This multicenter prospective study was performed to determine risk factors for knee prosthesis infection and the effect of timing doses of prophylactic low-molecular-weight heparins (LMWH) related to time of surgery on the risk of knee prosthesis infection. A total of 5496 consecutive patients who underwent total knee arthroplasty from 2005 to 2006 in 13 orthopedic centers were prospectively followed up for 6 months, and the incidence of knee prosthesis infection was recorded. A case control study was nested in the cohort. Case patients were matched to uninfected (control) patients, and the timing of perioperative LMWH was recorded as the main risk factor. Fifty patients developed postoperative knee prosthesis infection during the follow-up period, yielding an incidence of prosthesis infection of 0.91% (95% CI, 0.68%-1.20%). Forty-four patients were matched to 106 controls. Case patients received the first LMWH dose ±12 hours from the start of surgery more frequently than their control counterparts (odds ratio, 1.5; 95% CI, 0.73-3.0). After adjusting by main risk factors, no statistical association was found between close perioperative timing of LMWH and risk of prosthesis infection. Diabetes mellitus (adjusted odds ratio, 3.2; 95% CI, 1.2-8.8) and wound hematoma (adjusted odds ratio, 4.2; 95% CI, 1.1-16.5) were found to be independent risk factors for prosthesis infection.

Characterization of a large outbreak by CTX-M-1-producing Klebsiella pneumoniae and mechanisms leading to in vivo carbapenem resistance development.

All extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae isolates from patients admitted to and adult intensive care unit were prospectively documented from 2002 to 2005, when a large outbreak (51 patients affected) of multiresistant ESBL-producing Klebsiella pneumoniae infection was detected. The involvement of a single K. pneumoniae clone was demonstrated by pulsed-field gel electrophoresis. In addition to the ESBL-mediated resistance, the epidemic strain uniformly showed cross-resistance to ciprofloxacin, gentamicin, tobramycin, trimethoprim-sulfamethoxazole, and tetracycline, whereas resistance to the beta-lactam-beta-lactamase inhibitor combinations was variable. The ESBL involved was CTX-M-1, as demonstrated by isoelectric focusing, PCR amplification, and sequencing. CTX-M-1 as well as the aminoglycoside resistance determinants were encoded in a 50-kb plasmid that could be transferred to Escherichia coli only by transformation. In two of the infected patients, carbapenem resistance development (MICs of 8 to 12, 16, and >32 microg/ml for imipenem, meropenem, and ertapenem, respectively) was documented, both in clinical samples and in intestinal colonization studies. The analysis of the outer membrane proteins of the carbapenem-susceptible and -resistant isolates revealed that the former expressed only one of the two major porins, OmpK36, whereas the latter did not express either of them. In one of the cases, the lack of expression of OmpK36 was demonstrated to be mediated by the interruption of the coding sequence by the insertion sequence IS26. This is the first report of a large outbreak of CTX-M-1-producing Enterobacteriaceae and, curiously, the first documented description in the literature of CTX-M-1 in K. pneumoniae, despite the fact that this enzyme has been found in multiple species. Furthermore, we document and characterize for the first time carbapenem resistance development in CTX-M-1-producing Enterobacteriaceae.

Caracterización molecular de un brote por Enterococcus faecalis resistente a los glucopéptidos en una unidad de cuidados intensivos / Molecular characterization of a glycopeptide-resistant Enterococcus faecalis outbreak in an intensive care unit

Introducción. Entre enero y agosto de 2003 se aisló Enterococcus faecalis resistente a glucopéptidos en 8 pacientes ingresados en la unidad de cuidados intensivos (UCI). Métodos. La sensibilidad antibiótica se determinó por difusión con discos y Etest, la relación clonal por electroforesis de campo pulsado (PFGE) y la presencia del gen vanA por reacción en cadena de la polimerasa (PCR). Resultados y conclusiones. Todos los aislados fueron vanA1 y presentaron idéntico patrón de PFGE, lo cual puso de manifiesto un brote epidémico en la UCI (AU)

Introduction. Between January and August 2003 glycopeptide-resistant Enterococcus faecalis was isolated from eight patients admitted to the intensive care unit (ICU). Methods. Antibiotic susceptibility testing was performed by disk diffusion and the Etest, clonal relatedness of the isolates was studied by pulsed-field gel electrophoresis (PFGE), and the presence of vanA was investigated by PCR. Results and conclusions. All the isolates were vanA-positive and had an identical PFGE pattern, showing that an outbreak had occurred in our ICU (AU)

[Molecular characterization of a glycopeptide-resistant Enterococcus faecalis outbreak in an intensive care unit]. / Caracterización molecular de un brote por Enterococcus faecalis resistente a los glucopéptidos en una unidad de cuidados intensivos.

INTRODUCTION: Between January and August 2003 glycopeptide-resistant Enterococcus faecalis was isolated from eight patients admitted to the intensive care unit (ICU). METHODS: Antibiotic susceptibility testing was performed by disk diffusion and the Etest, clonal relatedness of the isolates was studied by pulsed-field gel electrophoresis (PFGE), and the presence of vanA was investigated by PCR. RESULTS AND CONCLUSIONS: All the isolates were vanA-positive and had an identical PFGE pattern, showing that an outbreak had occurred in our ICU.

[Consolidation of a Staphylococcus aureus multiresistant clone not related to the Iberian in a hospital from Mallorca]. / Consolidación de un clon multirresistente de Staphylococcus aureus no relacionado con el clon Ibérico en un hospital de Mallorca.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) was seldom isolated in our hospital until the first outbreak in 1999. A recently documented increase in antibiotic multiresistance in MRSA strains in our setting prompted the design of this molecular epidemiology study to investigate the basis for this tendency. METHODS: All MRSA isolates from clinical samples of patients admitted from July 2002 to June 2003 were studied. Susceptibility testing was performed by disk diffusion. Clonal relatedness of MRSA isolates was determined by pulsed-field gel electrophoresis (PFGE). Results were compared with data from MRSA isolates from patients admitted to the hospital in 1999-2000. RESULTS: MRSA was isolated in 110 patients (30% of patients with S. aureus-positive cultures). PFGE detected three major clones (in 93% of patients), all of which had been present in 1999-2000, although in different proportions. Whereas the predominant clone in 1999 was clone A (clone A 63%, clone B 20%), clone B was now found to predominate (clone B 58%, clone A 19%). None of these major clones were related to the five pandemic clones, including the Iberian clone, but two of them seemed to be related to the two most prevalent clones in Spain at this time. The new predominant clone was more resistant than the others, and showed uniform resistance to ciprofloxacin, erythromycin, clindamycin, and gentamicin. CONCLUSION: In recent years, a formerly predominant MRSA clone has been replaced by a multiresistant S. aureus clone that is unrelated to the Iberian clone.

Consolidación de un clon multirresistente de Staphylococcus aureus no relacionado con el clon Ibérico en un hospital de Mallorca / Consolidation of a Staphylococcus aureus multiresistant clone not related to the Iberian in a hospital from Mallorca

INTRODUCCIÓN. El primer brote de Staphylococcus aureusresistente a meticilina (SARM) en nuestro hospital se detectó en 1999. Recientemente se ha observado un incremento de la multirresistencia asociada a SARM, lo que ha motivado la realización de un estudio de epidemiología molecular para averiguar las bases de esta tendencia. MÉTODOS. Se documentaron todos los pacientes con aislamiento de SARM en muestras clínicas ingresados entre julio de 2002 y junio de 2003. El perfil de sensibilidad antibiótica se determinó mediante difusión con discos. El estudio de epidemiología molecular se realizó por electroforesis de campo pulsado (PFGE). Se han comparado los resultados obtenidos con datos históricos de 1999-2000. RESULTADOS. Se aisló SARM en 110 pacientes (30% de los pacientes con aislamiento de S. aureus). Mediante PFGE se detectaron tres clones mayoritarios (93% de pacientes). Estos clones estaban ya presentes en el estudio previo realizado en 1999-2000, aunque con un cambio en su distribución. Mientras que en 1999-2000 el mayoritario fue el clon A (clon A, 63%; clon B, 20%), actualmente ha sido desplazado por el clon B (clon B, 58%; clon A, 19%). Ninguno de los clones mayoritarios está relacionado con los cinco clones pandémicos (incluido el Ibérico)pero dos de ellos parecen relacionados con los dos clones más frecuentemente encontrados actualmente en España. El nuevo clon mayoritario presentó de forma uniforme resistencia a ciprofloxacino, eritromicina, clindamicina y gentamicina. CONCLUSIÓN. En los últimos años se ha producido un desplazamiento de un clon de SARM inicialmente predominante por otro multirresistente no relacionado con el clon Ibérico (AU)

INTRODUCTION. Methicillin-resistant Staphylococcus aureus(MRSA) was seldom isolated in our hospital until the first outbreak in 1999. A recently documented increase inantibiotic multiresistance in MRSA strains in our setting prompted the design of this molecular epidemiology study to investigate the basis for this tendency. METHODS. All MRSA isolates from clinical samples ofpatients admitted from July 2002 to June 2003 werestudied. Susceptibility testing was performed by disk diffusion. Clonal relatedness of MRSA isolates was determined by pulsed-field gel electrophoresis (PFGE). Results were compared with data from MRSA isolates from patients admitted to the hospital in 1999-2000. RESULTS. MRSA was isolated in 110 patients (30% ofpatients with S. aureus-positive cultures). PFGE detected three major clones (in 93% of patients), all of which had been present in 1999-2000, although in different proportions. Whereas the predominant clone in 1999 was clone A (clone A 63%, clone B 20%), clone B wasnow found to predominate (clone B 58%, clone A 19%).None of these major clones were related to the fivepandemic clones, including the Iberian clone, but twoof them seemed to be related to the two most prevalentclones in Spain at this time. The new predominant clone was more resistant than the others, and showed uniform resistance to ciprofloxacin, erythromycin, clindamycin,and gentamicin. CONCLUSION. In recent years, a formerly predominant MRSA clone has been replaced by a multiresistant S. aureus clone that is unrelated to the Iberian clone (AU)