[Thrombosis with Thrombocytopenia Syndrome following adenovirus vector-based vaccines to prevent COVID-19: epidemiology and clinical presentation in Spain]. / Síndrome de Trombosis con Trombocitopenia asociado a vacunas de adenovirus frente a la COVID-19: epidemiología y presentación clínica de la serie española.

BACKGROUND: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain. METHODS: We included all venous or arterial thrombosis with thrombocytopenia following adenovirus vector-based vaccines (AstraZeneca or Janssen) to prevent COVID-19 disease between February 1st and September 26th, 2021. We describe the crude rate and the standardized morbidity ratio. We assessed the predictors of mortality. RESULTS: Sixty-one cases were reported and 45 fulfilled eligibility criteria, 82% women. The crude TTS rate was 4/1,000,000 doses and 14-15/1,000,000 doses between 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 higher than the expected in patients younger than 49 years. Symptoms started 10 (interquartile range (IQR): 7-14) days after vaccination. Eighty percent (95% confidence interval (CI): 65-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (95% CI: 49-78%) had D-dimer >2000 ng/mL. Patients had multiple location thrombosis in 36% and fatal outcome in 24% cases. A platelet nadir <50,000 /µL (odds ratio (OR): 7.4; CI 95%: 1.2-47.5) and intracranial hemorrhage (OR: 7.9; IC95%: 1.3-47.0) were associated with fatal outcome. CONCLUSION: TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and/or D-dimer increase.

Significant ecological impact on the progression of fluoroquinolone resistance in Escherichia coli with increased community use of moxifloxacin, levofloxacin and amoxicillin/clavulanic acid.

OBJECTIVES: To determine trends in ciprofloxacin resistance and co-resistance to other antibiotic classes in blood isolates of Escherichia coli, and to investigate if there is an ecological relationship to the community use of fluoroquinolones and other antibiotics. METHODS: Forty-two Spanish hospitals of the European Antimicrobial Resistance Surveillance Network collected ciprofloxacin and other antibiotic susceptibility data for non-duplicate consecutive E. coli isolates from patients with bacteraemia between 2001 and 2009. The nationwide ambulatory use of antibiotics between 1997 and 2008 was determined by WHO methods, and the co-evolution of both parameters was further analysed. RESULTS: Of the 28 307 E. coli blood isolates, 27.9% were ciprofloxacin non-susceptible (CIPNS), increasing from 17.6% in 2001 to 32.7% in 2009. A continuous increase was observed between CIPNS and other resistances, including cephalosporin resistance due to the production of extended-spectrum ß-lactamases (ESBLs) and non-susceptibility to both amoxicillin/clavulanic acid and tobramycin. Although the total use of antibiotics did not increase, community use of levofloxacin, moxifloxacin and amoxicillin/clavulanic acid increased by 307.2%, 62.6% and 70.1%, respectively. Yearly rates of CIPNS E. coli strongly correlated with the use of levofloxacin, moxifloxacin and amoxicillin/clavulanic acid (r(2 )> 0.80; P < 0.005 in all cases). CONCLUSIONS: The rapid increase in CIPNS E. coli causing bacteraemia was closely related to the increase in resistance to amoxicillin/clavulanic acid, production of ESBLs and resistance to aminoglycosides. Community use of fluoroquinolones (mainly moxifloxacin and levofloxacin) and of amoxicillin/clavulanic acid represents a significant driver in the progression of fluoroquinolone resistance in bacteraemic E. coli.

Parallel increase in community use of fosfomycin and resistance to fosfomycin in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli.

OBJECTIVES: To document fosfomycin susceptibility of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC), analyse trends in fosfomycin use and investigate fosfomycin resistance in ESBL-EC isolated from urinary tract infections (UTIs). METHODS: Twenty-seven Spanish hospitals participating in the European Antimicrobial Resistance Surveillance Network were requested to collect up to 10 sequential ESBL-EC for centralized susceptibility testing and typing. EUCAST guidelines were followed for antibiotic susceptibility testing, and bla(ESBL) type, phylogroups and O25b serotype were determined by PCR and sequencing. In addition, the trend in fosfomycin resistance among ESBL-EC causing UTIs was determined in 9 of the 27 hospitals. Total fosfomycin use for ambulatory care was established by WHO-recommended methods. RESULTS: A total of 231 ESBL-EC (42.4% CTX-M-15, 34.2% SHV-12 and 23.4% CTX-M-14) were collected. The overall rate of fosfomycin resistance was 9.1%, but varied according to ESBL type (5.6% of CTX-M-14 isolates, 5.1% of SHV-12 and 15.3% of CTX-M-15). Of 67 O25b/B2 isolates, 11 (16.4%) were fosfomycin resistant. Predictors of infection with fosfomycin-resistant ESBL-EC were O25b/phylogroup B2 isolates, female gender and nursing home residence. Among 114 197 UTIs caused by E. coli 4740 (4.2%) were due to ESBL-EC. Fosfomycin resistance increased in these isolates from 4.4% (2005) to 11.4% (2009). The use of fosfomycin grew from 0.05 defined daily doses per 1000 inhabitants per day (1997) to 0.22 (2008), a 340% increase. CONCLUSIONS: Key factors related to increased fosfomycin resistance in ESBL-EC causing UTIs could be the rapid growth in community use of fosfomycin, the widespread distribution of the 025b/B2 E. coli clone and the existence of a susceptible population comprising women residing in nursing home facilities.

Increased amoxicillin-clavulanic acid resistance in Escherichia coli blood isolates, Spain.

To determine the evolution and trends of amoxicillin-clavulanic acid resistance among Escherichia coli isolates in Spain, we tested 9,090 blood isolates from 42 Spanish hospitals and compared resistance with trends in outpatient consumption. These isolates were collected by Spanish hospitals that participated in the European Antimicrobial Resistance Surveillance System network from April 2003 through December 2006.

Antibiotic resistance in Haemophilus influenzae decreased, except for beta-lactamase-negative amoxicillin-resistant isolates, in parallel with community antibiotic consumption in Spain from 1997 to 2007.

The susceptibility to 14 antimicrobial agents and the mechanisms of aminopenicillin resistance were studied in 197 clinical isolates of Haemophilus influenzae--109 isolated in 2007 (study group) and 88 isolated in 1997 (control group). Community antibiotic consumption trends were also examined. H. influenzae strains were consecutively isolated from the same geographic area, mostly from respiratory specimens from children and adults. Overall, amoxicillin resistance decreased by 8.4% (from 38.6 to 30.2%). Beta-lactamase production decreased by 15.6% (from 33 to 17.4%, P = 0.01), but amoxicillin resistance without beta-lactamase production increased by 7.1% (from 5.7 to 12.8%). All beta-lactamase-positive isolates were TEM-1, but five different promoter regions were identified, with Pdel being the most prevalent in both years, and Prpt being associated with the highest amoxicillin resistance. A new promoter consisting of a double repeat of 54 bp was detected. Community consumption of most antibiotics decreased, as did the geometric means of their MICs, but amoxicillin-clavulanic acid and azithromycin consumption increased by ca. 60%. For amoxicillin-clavulanic acid, a 14.2% increase in the population with an MIC of 2 to 4 microg/ml (P = 0.02) was observed; for azithromycin, a 21.2% increase in the population with an MIC of 2 to 8 microg/ml (P = 0.0005) was observed. In both periods, the most common gBLNAR (i.e., H. influenzae isolates with mutations in the ftsI gene as previously defined) patterns were IIc and IIb. Community consumption of trimethoprim-sulfamethoxazole decreased by 54%, while resistance decreased from 50 to 34.9% (P = 0.04). Antibiotic resistance in H. influenzae decreased in Spain from 1997 to 2007, but surveillance should be maintained since new forms of resistances may be developing.

[Acute hepatitis associated with Colpachi intake. Apropros of 5 cases]. / Hepatitis aguda asociada al consumo de Copalchi. A propósito de 5 casos.

The use of herbal medicines believed to have therapeutic properties is becoming increasingly widespread. These medicines are usually taken by patients on their own initiative and physicians are often unaware of which patients are taking these substances. Herbal medicines can be taken in the form of teas, powders, and liquid extracts. In the last few years, it has come to light that these natural remedies are not free of risks, especially the risk of interaction with other drugs or hepatotoxicity, ranging from asymptomatic forms to massive hepatic necrosis. We describe a series of 5 patients notified to the Spanish Pharmacovigilance System of medicinal products for human use. All the patients developed acute hepatitis during Colpachi treatment lasting several months, which resolved after discontinuing intake of this substance. Systematic examination of the literature revealed the existence of 6 other reported cases of suspected Colpachi-induced hepatotoxicity.

Surveillance of outpatient antibiotic consumption in Spain according to sales data and reimbursement data.

OBJECTIVES: National data on antibiotic consumption are needed in order to interpret trends in antibiotic resistance. We compared antibiotic prescription reimbursement data and sales data in Spain. METHODS: Data covering the years 2002, 2004 and 2005 were examined. Reimbursement data for ambulatory care were provided by the Spanish Agency for Medicines and Healthcare Products and sales data by International Medical Statistics Health. Quantities were standardized using the defined daily dose per 1000 inhabitants per day (DID) in accordance with the anatomical therapeutic classification. RESULTS: Sales data increased from 26.33 DID in 2002 to 28.12 DID in 2004 and 28.93 DID in 2005. Estimates based on equivalent reimbursement data were ~30% lower and increased from 18.01 DID in 2002 to 18.48 DID in 2004 and 19.29 DID in 2005. The differences were greatest for amoxicillin, amoxicillin/clavulanic acid, clarithromycin and cefuroxime. CONCLUSIONS: Antibiotic consumption as estimated from reimbursement data is substantially less than that from sales data. This finding has major implications for national surveillance of antibiotic consumption.

Ampicillin-resistant non-beta-lactamase-producing Haemophilus influenzae in Spain: recent emergence of clonal isolates with increased resistance to cefotaxime and cefixime.

The sequence of the ftsI gene encoding the transpeptidase domain of penicillin-binding protein 3 (PBP 3) was determined for 354 nonconsecutive Haemophilus influenzae isolates from Spain; 17.8% of them were ampicillin susceptible, 56% were beta-lactamase nonproducing ampicillin resistant (BLNAR), 15.8% were beta-lactamase producers and ampicillin resistant, and 10.4% displayed both resistance mechanisms. The ftsI gene sequences had 28 different mutation patterns and amino acid substitutions at 23 positions. Some 93.2% of the BLNAR strains had amino acid substitutions at the Lys-Thr-Gly (KTG) motif, the two most common being Asn526 to Lys (83.9%) and Arg517 to His (9.3%). Amino acid substitutions at positions 377, 385, and 389, which conferred cefotaxime and cefixime MICs 10 to 60 times higher than those of susceptible strains, were found for the first time in Europe. In 72 isolates for which the repressor acrR gene of the AcrAB efflux pump was sequenced, numerous amino acid substitutions were found. Eight isolates with ampicillin MICs of 0.25 to 2 microg/ml showed changes that predicted the early termination of the acrR reading frame. Pulsed-field gel electrophoresis analysis demonstrated that most BLNAR strains were genetically diverse, although clonal dissemination was detected in a group of isolates presenting with increased resistance to cefotaxime and cefixime. Background antibiotic use at the community level revealed a marked trend toward increased amoxicillin-clavulanic acid consumption. BLNAR H. influenzae strains have arisen by vertical and horizontal spread and have evolved to adapt rapidly to the increased selective pressures posed by the use of oral penicillins and cephalosporins.

Antimicrobial-resistant invasive Escherichia coli, Spain.

Surveillance System. A network of 32 Spanish hospitals, serving approximately 9.6 million persons, submitted antimicrobial-susceptibility data on 7,098 invasive Escherichia coli species (2001-2003). Resistance to ampicillin, cotrimoxazole, ciprofloxacin, gentamicin, and tobramycin was found at rates of 59.9%, 32.6%, 19.3%, 6.8%, and 5.3%, respectively. Resistance to multiple drugs increased from 13.8% in 2001 to 20.6% in 2003 (p <0.0001). Antimicrobial consumption data were obtained from the Spanish National Health System. In spite of decreased cephalosporin and beta-lactam use, overall extended-spectrum beta-lactamase production increased from 1.6% (2001) to 4.1% (2003) (p <0.0001), mainly due to the rising prevalence of cefotaximases. Resistance to ciprofloxacin significantly increased, mostly in community-onset infections, which coincided with a rise in community quinolone use. Cotrimoxazole resistance remained stable at approximately 30%, even though its use was dramatically reduced.

Trends in antimicrobial resistance in 1,968 invasive Streptococcus pneumoniae strains isolated in Spanish hospitals (2001 to 2003): decreasing penicillin resistance in children's isolates.

To address the public health problem of antibiotic resistance, the European Union (EU) founded the European Antimicrobial Resistance Surveillance System. A network of 40 hospitals that serve approximately 30% of the Spanish population (about 12 million) participated. Each laboratory reported data on antimicrobial susceptibility testing using standard laboratory procedures that were evaluated by an external quality control program. The antibiotic consumption data were obtained from the National Health System. We compared the antibiotic susceptibility of Spanish isolates of invasive Streptococcus pneumoniae (2001 to 2003) with antibiotic consumption. Invasive S. pneumoniae was isolated from 1,968 patients, 20% of whom were children at or below the age of 14 years. Of non-penicillin-susceptible strains (35.6%; 95% confidence interval, 34 to 37.2), 26.4% were considered intermediate and 9.2% were considered resistant. Between 2001 and 2003, penicillin resistance decreased from 39.5 to 33% overall and from 60.4 to 41.2% in children at or below the age of 14 years (P = 0.002). Resistance to erythromycin was at 26.6%, and coresistance with penicillin was at 19.1%. Of total isolates, the ciprofloxacin MIC was >2 mug/ml for 2.1%, with numbers increasing from 0.4% (2001) to 3.9% (2003). Total antibiotic use decreased from 21.66 to 19.71 defined daily doses/1,000 inhabitants/day between 1998 and 2002. While consumption of broad-spectrum penicillins, cephalosporins, and erythromycin declined, use of amoxicillin-clavulanate and quinolones increased by 17.5 and 27%, respectively. The frequency of antibiotic resistance in invasive S. pneumoniae in Spain was among the highest in the EU. However, a significant decrease in penicillin resistance was observed in children. This decrease coincided with the introduction of a heptavalent conjugate pneumoccocal vaccine (June 2001) and with a global reduction in antibiotic consumption levels.

Analysis of invasive Haemophilus influenzae infections after extensive vaccination against H. influenzae type b.

Little clinical and microbiological information is available about invasive Haemophilus influenzae infection after widespread vaccination against H. influenzae type b (Hib). We conducted an active community surveillance study on invasive H. influenzae during a 2-year period in a community of more than 5 million people after vaccination against Hib in children was introduced. The median incidence was 16.3 cases/100000 persons per year in children less than 1-year-old and 4.41 cases/100000 persons in children less than <5 years old. The highest incidence in adults was observed in patients greater than 70 years old. Clinical diagnoses included bacteremia, pneumonia, and meningitis. Of the H. influenzae-infected patients, 74.3% had underlying predisposing conditions, including impaired immunity and respiratory diseases. A total of 73.6% of the isolates were nontypeable and 16.5, 6.6, and 3.3% were types b, f, and e, respectively. Infections due to capsulated strains b, e, and f were evenly distributed between children and adults. Ampicillin and cotrimoxazole resistance occurred at frequencies of 24.2 and 48.4%, respectively. Antibiotic resistance was more prevalent in capsulated than in noncapsulated H. influenzae. Invasive isolates were highly resistant to antibiotics that were used infrequently in the community. Nontypeable H. influenzae were genetically much more heterogeneous than capsulated strains. Capsule-deficient mutants (b(-)) were not detected. Plasmid carriage was linked to antibiotic resistance and capsulated strains. Over the study period, the incidence of invasive H. influenzae infections, either encapsulated or not, did not increase. In the post-Hib vaccination era, most invasive infections were due to noncapsulated strains and occurred in the extreme ages of life in patients with predisposing conditions.

Sistema español de farmacovigilancia de las vacunas / Spanish pharmacovigilance system of vaccines

No disponible

Hepatitis aguda asociada al consumo de Copalchi. A propósito de 5 casos / Acute hepatitis associated with Colpachi intake. Apropros of 5 cases

El uso de hierbas medicinales con supuesta actividad terapéutica está creciendo. Estas medicinas las suele tomar el paciente por propia iniciativa y, a menudo, con desconocimiento por parte de su médico. Se pueden tomar en forma de infusiones o extractos líquidos. En los últimos años se ha ido conociendo que estos remedios naturales no están exentos de riesgo, especialmente riesgo de interacción con otras medicaciones o hepatotoxicidad que puede variar desde formas asintomáticas a necrosis hepática masiva. Describimos 5 pacientes notificados al Sistema Español de Farmacovigilancia de productos medicinales de uso humano. Todos los pacientes desarrollaron hepatitis aguda durante el tratamiento con Colpachi durante varios meses, que se resolvió al parar la toma de esta sustancia. La revisión sistemática de la literatura revela la existencia de otras 6 notificaciones de hepatotoxicidad inducida por Colpachi

The use of herbal medicines believed to have therapeutic properties is becoming increasingly widespread. These medicines are usually taken by patients on their own initiative and physicians are often unaware of which patients are taking these substances. Herbal medicines can be taken in the form of teas, powders, and liquid extracts. In the last few years, it has come to light that these natural remedies are not free of risks, especially the risk of interaction with other drugs or hepatotoxicity, ranging from asymptomatic forms to massive hepatic necrosis. We describe a series of 5 patients notified to the Spanish Pharmacovigilance System of medicinal products for human use. All the patients developed acute hepatitis during Colpachi treatment lasting several months, which resolved after discontinuing intake of this substance. Systematic examination of the literature revealed the existence of 6 other reported cases of suspected Colpachi-induced hepatotoxicity