Safety and Efficacy of Prolonged Use of Dalbavancin in Bone and Joint Infections.

Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included. Staphylococcus epidermidis and Staphylococcus aureus were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when >2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency.

Efficacy of Idursulfase therapy in patients with Mucopolysaccharidosis type II who initiated enzyme replacement therapy in adult age. A systematic review of the literature.

BACKGROUND: Enzyme replacement therapy (ERT) has been shown to decrease urine glycosaminoglycans (uGAGs) and liver and spleen volumes, and to improve clinical symptoms in mucopolysaccharidosis type II (MPS-II) patients. METHODS: A systematic search of the literature, from inception to August 2017, was conducted to identify randomized trials or observational studies including ≥1 MPS-II patients with ERT initiated in adult age (≥16 years) and evaluating ERT efficacy. Evidence was rated according to GRADE criteria. Common efficacy outcomes of the clinical studies were analyzed. Case reports were separately evaluated. RESULTS: One randomized clinical trial, 4 observational studies and 5 case reports were selected. ERT decreased uGAG levels and liver and spleen size with moderate evidence level and led to anti-ERT antibody and IRRS development in a significant proportion of patients with moderate evidence level. There were no conclusive results for beneficial effects on 6MWT, respiratory, cardiac and neurological function, joint mobility, sleep disorders of respiratory origin, and quality of life. LIMITATIONS: Excluding one observational study, all others were not conducted specifically in the target population (ERT ≥16 years). Data were from subgroup analyses of selected studies. There was a great heterogeneity between study designs and clinical outcomes evaluated. CONCLUSIONS: ERT improves uGAGs and liver/spleen volume with a moderate evidence level in MPS-II patients initiating therapy as adults, although the putative associated clinical benefit is unclear.

Executive summary of management of prosthetic joint infections. Clinical practice guidelines by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

The incidence of prosthetic joint infection (PJI) is expected to increase in the coming years. PJI has serious consequences for patients, and high costs for the health system. The complexity of these infections makes it necessary to organize the vast quantity of information published in the last several years. The indications for the choice of a given surgical strategy and the corresponding antimicrobial therapy are specifically reviewed. The authors selected clinically relevant questions and then reviewed the available literature in order to give recommendations according to a pre-determined level of scientific evidence. The more controversial aspects were debated, and the final composition was agreed at an ad hoc meeting. Before its final publication, the manuscript was made available online in order that all SEIMC members were able to read it and make comments and suggestions.

Is reduced vancomycin susceptibility a factor associated with poor prognosis in MSSA bacteraemia?

OBJECTIVES: The known data about the influence of vancomycin MIC on Staphylococcus aureus bacteraemia are contradictory. Our objective was to study the possible impact of vancomycin MIC ≥1.5 mg/L on short- and medium-term mortality. METHODS: A prospective cohort study was carried out from March 2008 to January 2011 on adult patients with MSSA bacteraemia admitted to a tertiary hospital located in Seville (Spain). We studied the relationship between vancomycin MIC, accessory gene regulator (agr) type and absence of δ-haemolysin and poor prognosis. All isolates were genotyped by PFGE. Multivariate analysis, including a propensity score for having a vancomycin MIC of ≥1.5 mg/L, was performed by Cox regression. RESULTS: One hundred and thirty-five episodes of bacteraemia due to MSSA were included in the analysis. Twenty-nine (21.5%) isolates had a vancomycin MIC of ≥1.5 mg/L by Etest. There were no differences in agr distribution or absence of δ-haemolysin between isolates with reduced vancomycin susceptibility (RVS) and those without. RVS was not more frequent in specific clones; RVS was not associated with higher 14 or 30 day crude mortality (relative risk = 0.44, 95% CI = 0.14-1.35; and relative risk = 1.01, 95% CI = 0.52-1.96) rates, and it did not show higher rates of complicated bacteraemia (14.2% versus 13.8%, P = 0.61). Cox regression analysis did not significantly modify the results for 14 day mortality (HR = 0.39, 95% CI = 0.11-1.34) or 30 day mortality (HR = 0.89, 95% CI = 0.39-2.04). CONCLUSIONS: Contrary to previously published data, we did not find a relationship between RVS and higher mortality in patients with MSSA bacteraemia and we did not find a link with higher complicated bacteraemia rates.

Are hip hemiarthroplasty and total hip arthroplasty infections different entities? The importance of hip fractures.

Hip hemiarthroplasty (HHA) and total hip arthroplasty (THA) infections are usually considered as one entity; however, they may show important differences. We analyze these differences, as well as predictors of treatment failure (TF) and poor functional status among patients with prosthetic hip infections (PHIs). A multicenter cohort study of consecutive patients with PHIs was performed. The main outcome variable was TF after the first surgical treatment performed to treat the infection. Multivariate analysis was used to identify predictors of TF. A total of 127 patients with PHI were included (43 HHA, 84 THA). Patients with HHA infections were more frequently women (88% vs. 54%; p < 0.001), had comorbidities (86% vs. 67%, p = 0.02), and were older (median age 79 vs. 65 years, p < 0.001), and the reason for arthroplasty was more frequently a fracture (100% vs. 18%, p < 0.001). Failure of initial treatment and crude mortality were more frequent among HHA patients (44% vs. 23%, p = 0.01 and 28% vs. 7%, p = 0.001, respectively). However, HHA was not associated with TF in the multivariate analysis when hip fracture was considered; thus, variables independently associated with TF were hip fracture, inadequate surgical management, prosthesis retention, and higher C-reactive protein level. Failure of the first surgical treatment was associated with poorer functional status. HHA and THA infections showed significant differences in epidemiology, clinical features, and outcome. Although patients with HHA infections had a higher risk of TF, this was related to the reason for hip implant: a hip fracture. Success of the initial management of infection is a predictor of better clinical and functional outcome.

EPITRANS. Quality assessment of the epilepsy transition process.

OBJECTIVE: To analyze the differences in clinical management during the epilepsy transition process from pediatric to adult care and to determine the quality of life and degree of satisfaction of patients and caregivers during the transition. METHODS: This is a longitudinal study including patients with epilepsy transferred from pediatric to adult epilepsy care between 2013 and 2017. Patients had a minimum follow-up of 3 years before the transition visit and at least 3 years consulting in the adults section. Clinical characteristics were retrieved from the medical chart. Quality of life and satisfaction questionnaires were administered by online access to patients and caregivers at the end of the adult follow-up period. RESULTS: 99 patients (50.5 % women, mean transition age 16.5 ± 1 years old) were included. Before the transition visit, 90 % of patients received a transition discussion and 88 % had a formal clinical report. In the pediatric period, patients were visited more frequently, had more EEGs and genetic studies, and were seen by the same neuropediatrician (P<0.05). In the adult period, patients underwent a larger number of prolonged video EEGs and were prescribed polytherapy more often (P<0.05). Quality of life remained steady during the entire transition, but satisfaction with the care received was significantly higher during the pediatric period. CONCLUSIONS: Significant differences were seen in epilepsy care during transition from pediatric to adult management, and this had an impact on the degree of satisfaction reported by patients and caregivers. Our results provide evidence of the potential value of development and early implementation of a protocolled transition program.

Knowledge and perceptions of junior and senior Spanish resident doctors about antibiotic use and resistance: results of a multicenter survey.

BACKGROUND: Antibiotic resistance has been recognized as a worldwide problem. Our aim was to assess the perceptions of Spanish residents about antibiotic use and resistance. METHODS: An online cross-sectional survey was conducted on all resident doctors in five teaching hospitals (September to November 2010). A link to the questionnaire was e-mailed to 844 doctors. The questionnaire collected demographical characteristics, residents' knowledge about microorganisms of known clinical relevance, their habits in the antibiotic prescription process, and their perceptions on the activities aimed to improve antibiotic use. RESULTS: We received 279 responses corresponding to 33.05% of all targeted residents. The response rate was higher among junior than among senior residents (39.95% vs. 26.12%; p<0.05). Residents of all hospitals, specialties and seniority mostly considered that antimicrobial resistance was a significant problem at national level (94.3%), at their institution (91.3%), and for their daily practice (83.8%). Residents considered their training regarding antibiotics insufficient, although up to 86.5% had prescribed antibiotics in the last month. They preferred the availability of local antibiotic guidelines (65%), specific teaching sessions, specific antimicrobial management teams or readily accessible advice from a group or an infectious diseases specialist, to improve antibiotic prescribing, rather than other restrictive interventions. CONCLUSIONS: Most residents at the hospitals surveyed believed that antibiotic resistance was a serious problem. The results of this survey provided very important information to optimize adherence to Antimicrobial Stewardship Programs (ASPs). Educational strategies and non-restrictive aids are the most valuable interventions, which ASPs should capitalize on to improve antimicrobial prescription.

Surgical Infection Reduction Program of the Observatory of Surgical Infection (PRIQ-O): Delphi prioritization and consensus document on recommendations for the prevention of surgical site infection.

Surgical site infection is the most frequent and avoidable complication of surgery, but clinical guidelines for its prevention are insufficiently followed. We present the results of a Delphi consensus carried out by a panel of experts from 17 Scientific Societies with a critical review of the scientific evidence and international guidelines, to select the measures with the highest degree of evidence and facilitate their implementation. Forty measures were reviewed and 53 recommendations were issued. Ten main measures were prioritized for inclusion in prevention bundles: preoperative shower; correct surgical hand hygiene; no hair removal from the surgical field or removal with electric razors; adequate systemic antibiotic prophylaxis; use of minimally invasive approaches; skin decontamination with alcoholic solutions; maintenance of normothermia; plastic wound protectors-retractors; intraoperative glove change; and change of surgical and auxiliary material before wound closure.

An incidental finding in newborn screening leading to the diagnosis of a patient with ECHS1 mutations.

Short-chain enoyl-CoA hydratase (ECHS1) is a mitochondrial beta-oxidation enzyme involved in the metabolism of acyl-CoA fatty acid esters, as well as in valine metabolism. ECHS1 deficiency has multiple manifestations, including Leigh syndrome early at birth or in childhood with poor prognosis, to cutis laxa, exercise-induced dystonia and congenital lactic acidosis. Here we describe the case of a newborn with mutations in ECHS1 that caught our attention after the incidental finding of 3-hydroxy-butyryl\3-hydroxy-isobutyryl\malonylcarnitine (C4OH\C3DC) and tiglylcarnitine (C5:1) on blood spot in the newborn screening (NBS) program. Diagnosis was suspected based on the analysis of organic acids on dried urine spot. A moderate increase of 2-methyl-2,3-dihydroxybutyric acid, was detected, which is a known marker of this disease. Exome analysis showed c.404A>G (p.Asn135Ser) mutation in homozygosis in the ECHS1 gene. The child was therefore admitted to the hospital. Initial examination showed little response to auditory stimuli and mild hypertonia of the extremities. Clinical deterioration was evident at 4 months of age, including neurological and cardiac involvement, and the patient died at 5 months of age. This case illustrates how an incidental detection in the NBS Program can lead to the diagnosis ECHS1 deficiency. Although it is a severe disease, with no treatment available, early detection would allow adequate genetic counseling avoiding the odyssey that suffered most of these families.

Suppressive antibiotic therapy in prosthetic joint infections: a multicentre cohort study.

OBJECTIVES: The aim was to describe the effectiveness of suppressive antibiotic treatment (SAT) in routine clinical practice when used in situations in which removal of a prosthetic implant is considered essential for the eradication of an infection, and it cannot be performed. METHODS: This was a descriptive retrospective and multicentre cohort study of prosthetic joint infection (PJI) cases managed with SAT. SAT was considered to have failed if a fistula appeared or persisted, if debridement was necessary, if the prosthesis was removed due to persistence of the infection or if uncontrolled symptoms were present. RESULTS: In total, 302 patients were analysed. Two hundred and three of these patients (67.2%) received monotherapy. The most commonly used drugs were tetracyclines (39.7% of patients) (120/302) and cotrimoxazole (35.4% of patients) (107/302). SAT was considered successful in 58.6% (177/302) of the patients (median time administered, 36.5 months; IQR 20.75-59.25). Infection was controlled in 50% of patients at 5 years according to Kaplan-Meier analysis. Resistance development was documented in 15 of 65 (23.1%) of the microbiologically documented cases. SAT failure was associated with age <70 years (sub-hazard ratio (SHR) 1.61, 95% CI 1.1-2.33), aetiology other than Gram-positive cocci (SHR 1.56, 95% CI 1.09-2.27) and location of the prosthesis in the upper limb (SHR 2.4, 95% CI 1.5-3.84). SAT suspension was necessary due to adverse effects in 17 of 302 patients (5.6%). CONCLUSIONS: SAT offers acceptable results for patients with PJI when surgical treatment is not performed or when it fails to eradicate the infection.

Development and validation of baseline, perioperative and at-discharge predictive models for postsurgical prosthetic joint infection.

OBJECTIVES: To develop and validate baseline, perioperative and at-discharge risk-scoring systems for postsurgical prosthetic joint infection (PJI) in patients undergoing arthroplasty. METHODS: A multicentre prospective cohort study of patients undergoing hip and knee arthroplasty was performed. Patients were randomly assigned (2:1) to a derivation cohort (DC) or a validation cohort (VC). Multivariable predictive models of PJI were constructed at baseline (preoperative period), perioperative (adding perioperative variables) and at-discharge (adding wound state at discharge). The predictive ability of the models and scores was evaluated by area under the receiving operating characteristic curves (AUROC). RESULTS: The DC and VC included 2324 and 1245 patients, respectively. Baseline model included total hip arthroplasty (THA), revision arthroplasty (RA), Charlson index and obesity. The AUROC for the score was 0.75 and 0.78 in the DC and VC, respectively. Perioperative model included THA, RA, obesity, National Nosocomial Infections Surveillance (NNIS) index ≥2, significant wound bleeding and superficial surgical site infection; the AUROC was 0.81 and 0.77 in the DC and VC, respectively. The at-discharge model included THA, RA, obesity, NNIS index ≥2, superficial surgical site infection and high-risk wound; the AUROC was 0.82 and 0.84 in the DC and VC, respectively. A score ≥8 points provided 99% negative predictive values for all models. CONCLUSIONS: Simple scores for predicting PJI at three different moments of care in patients undergoing arthroplasty were developed and validated. The scores allow early and accurate identification of high-risk individuals in whom enhanced preventive measures and follow-up may be needed. Further external validation is needed.

Transition of patients with mucopolysaccharidosis from paediatric to adult care.

Mucopolysaccharidoses (MPS) are rare disorders associated with enzyme deficiencies, resulting in glycosaminoglycan (GAG) accumulation in multiple organ systems. As patients increasingly survive to adulthood, the need for a smooth transition into adult care is essential. Using case studies, we outline strategies and highlight the challenges of transition, illustrating practical solutions that may be used to optimise the transition process for patients with MPS disorders. Seven MPS case studies were provided by four European inherited metabolic disease centres; six of these patients transferred to an adult care setting and the final patient remained under paediatric care. Of the patients who transferred, age at the start of transition ranged between 14 and 18 years (age at transfer ranged from 16 to 19 years). While there were some shared features of transition strategies, they varied in duration, the healthcare professionals involved and the management of adult patients with MPS. Challenges included complex symptoms, patients' unwillingness to attend appointments with unfamiliar team members and attachment to paediatricians. Challenges were resolved by starting transition at an early age, educating patients and families, and providing regular communication with and reassurance to the patient and family. Sufficient time should be provided to allow patients to understand their responsibilities in the adult care setting while feeling assured of continued support from healthcare professionals. The involvement of a coordinated multidisciplinary team with expertise in MPS is also key. Overall, transition strategies must be comprehensive and individualised to patients' needs.

Genetic analysis of 27 Spanish patients with hemiplegic migraine, basilar-type migraine and childhood periodic syndromes.

Familial hemiplegic migraine (FHM) is a rare type of migraine with aura. Mutations in three genes have been described in FHM patients: CACNA1A (FHM1), ATP1A2 (FHM2) and SCN1A (FHM3). We screened 27 Spanish patients with hemiplegic migraine (HM), basilar-type migraine or childhood periodic syndromes (CPS) for mutations in these three genes. Two novel CACNA1A variants, p.Val581Met and p.Tyr1245Cys, and a previously annotated change, p.Cys1534Ser, were identified in individuals with HM, although they have not yet been proven to be pathogenic. Interestingly, p.Tyr1245Cys was detected in a patient displaying a changing, age-specific phenotype that began as benign paroxysmal torticollis of infancy, evolving into benign paroxysmal vertigo of childhood and later becoming HM. This is the first instance of a specific non-synonymous base change being described in a subject affected with CPS. The fact that the molecular screen identified non-synonymous changes in < 15% of our HM patients further stresses the genetic heterogeneity underlying the presumably monogenic forms of migraine.

Methylmalonic acidaemia: examination of genotype and biochemical data in 32 patients belonging to mut, cblA or cblB complementation group.

Methylmalonic acidaemia (MMA) is a genetic disorder caused by defects in methylmalonyl-CoA mutase or in any of the different proteins involved in the synthesis of adenosylcobalamin. The aim of this work was to examine the biochemical and clinical phenotype of 32 MMA patients according to their genotype, and to study the mutant mRNA stability by real-time PCR analysis. Using cellular and biochemical methods, we classified our patient cohort as having the MMA forms mut (n = 19), cblA (n = 9) and cblB (n = 4). All the mut (0) and some of the cblB patients had the most severe clinical and biochemical manifestations, displaying non-inducible propionate incorporation in the presence of hydroxocobalamin (OHCbl) in vitro and high plasma odd-numbered long-chain fatty acid (OLCFA) concentrations under dietary therapy. In contrast, mut (-) and cblA patients exhibited a milder phenotype with propionate incorporation enhanced by OHCbl and normal OLCFA levels under dietary therapy. No missense mutations identified in the MUT gene, including mut (0) and mut (-) changes, affected mRNA stability. A new sequence variation (c.562G>C) in the MMAA gene was identified. Most of the cblA patients carried premature termination codons (PTC) in both alleles. Interestingly, the transcripts containing the PTC mutations were insensitive to nonsense-mediated decay (NMD).

The methodology of surveillance for antimicrobial resistance and healthcare-associated infections in Europe (SUSPIRE): a systematic review of publicly available information.

OBJECTIVES: Surveillance is a key component of any control strategy for healthcare-associated infections (HAIs) and antimicrobial resistance (AMR), and public availability of methodologic aspects is crucial for the interpretation of the data. We sought to systematically review publicly available information for HAIs and/or AMR surveillance systems organized by public institutions or scientific societies in European countries. METHODS: A systematic review of scientific and grey literature following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed. Information on HAIs and/or AMR surveillance systems published until 31 October 2016 were included. RESULTS: A total of 112 surveillance systems were detected; 56 from 20 countries were finally included. Most exclusions were due to lack of publicly available information. Regarding AMR, the most frequent indicator was the proportion of resistant isolates (27 of 34 providing information, 79.42%); only 18 (52.9%) included incidence rates; the data were only laboratory based in 33 (78.5%) of the 42 providing this information. Regarding HAIs in intensive care units, all 22 of the systems providing data included central line-associated bloodstream infections, and 19 (86.3%) included ventilator-associated pneumonia and catheter-associated urinary tract infections; incidence density was the most frequent indicator. Regarding surgical site infections, the most frequent procedures included were hip prosthesis, colon surgery and caesarean section (21/22, 95.5%). CONCLUSIONS: Publicly available information about the methods and indicators of the surveillance system is frequently lacking. Despite the efforts of European Centre for Disease Control and Prevention (ECDC) and other organizations, wide heterogeneity in procedures and indicators still exists.

Transition from paediatric care to adult care for patients with mucopolysaccharidosis. / Transición desde la asistencia pediátrica a la adulta en pacientes con mucopolisacaridosis.

Mucopolysaccharidosis are multisystem diseases that require large multidisciplinary teams for their care. Specific recommendations are therefore needed for the transition from childhood to adulthood in this patient group. To overcome the barriers that might arise during the transition, the authors consider it essential to implement a flexible plan with a coordinator for the entire process, systematising the information through a standardised paediatric discharge report and educating the patient and their family about the disease, showing the characteristics of the healthcare system in this new stage. The final objective is that, once the transition to adulthood has been completed, the patient's autonomy and potential development are maximised and that the patient receives appropriate healthcare during this transition.

Incidence and distribution pattern of Rickettsia felis in peridomestic fleas from Andalusia, Southeast Spain.

The presence of Rickettsia felis was investigated in three species of pulicid fleas (Ctenocephalides felis, Ctenocephalides canis and Pulex irritans) collected in 38 locales in Andalusia (Spain) over the period 1999-2004. Amplification of a fragment of OmpB gene was positive in 54.17 % of lots of Ct. felis. The identity of the PCR bands was confirmed as R. felis by sequence data obtained directly from the PCR amplicon. No rickettsia was found in Ct. canis nor P. irritans.

Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study.

It is important to know the spectrum of the microbial aetiology of prosthetic joint infections (PJIs) to guide empiric treatment and establish antimicrobial prophylaxis in joint replacements. There are no available data based on large contemporary patient cohorts. We sought to characterize the causative pathogens of PJIs and to evaluate trends in the microbial aetiology. We hypothesized that the frequency of antimicrobial-resistant organisms in PJIs has increased in the recent years. We performed a cohort study in 19 hospitals in Spain, from 2003 to 2012. For each 2-year period (2003-2004 to 2011-2012), the incidence of microorganisms causing PJIs and multidrug-resistant bacteria was assessed. Temporal trends over the study period were evaluated. We included 2524 consecutive adult patients with a diagnosis of PJI. A microbiological diagnosis was obtained for 2288 cases (90.6%). Staphylococci were the most common cause of infection (1492, 65.2%). However, a statistically significant rising linear trend was observed for the proportion of infections caused by Gram-negative bacilli, mainly due to the increase in the last 2-year period (25% in 2003-2004, 33.3% in 2011-2012; p 0.024 for trend). No particular species contributed disproportionally to this overall increase. The percentage of multidrug-resistant bacteria PJIs increased from 9.3% in 2003-2004 to 15.8% in 2011-2012 (p 0.008), mainly because of the significant rise in multidrug-resistant Gram-negative bacilli (from 5.3% in 2003-2004 to 8.2% in 2011-2012; p 0.032). The observed trends have important implications for the management of PJIs and prophylaxis in joint replacements.