Predictors of mortality and clinical characteristics among carbapenem-resistant or carbapenemase-producing Enterobacteriaceae bloodstream infections in Spanish children.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging problem in the paediatric population worldwide with high mortality rates in bloodstream infection (BSI). OBJECTIVES: To evaluate predictors of 30 day mortality in CRE BSI in a paediatric cohort. METHODS: A retrospective observational single-centre study (December 2005-August 2018) was conducted. Cases of CRE BSI in children 0 to 16 years were included. Microbiological identification (MALDI Biotyper) and antimicrobial susceptibility testing (Vitek2® and MicroScan panel NBC44) according to EUCAST breakpoints were performed. PCR OXVIKP® was used to confirm carbapenemase genes (OXA-48, VIM, KPC, NDM). Demographic characteristics, underlying diseases, source of bacteraemia, antimicrobial therapy and outcomes were collected from medical records. Survival analysis to establish predictors of 30 day mortality was performed. RESULTS: Thirty-eight cases were included; 76.3% were hospital-acquired infections and 23.7% related to healthcare. All patients had at least one underlying comorbidity and 52.6% were recipients of an organ transplant. VIM carbapenemase was the predominant mechanism (92.1%). Previous CRE colonization or infection rate was 52.6%. Intestinal tract (26.3%) and vascular catheter (21.1%) were the most common sources of infection. Crude mortality within 30 days was 18.4% (7/38); directly related 30 day mortality was 10.5%. Conditions associated with an increment in 30 day mortality were intensive care admission and inadequate empirical therapy (P < 0.05). Combination-antibiotic targeted treatment and a low meropenem MIC were not related to improved survival. CONCLUSIONS: CRE BSI mortality rate is high. The most important factor related to 30 day survival in our CRE BSI cohort in children was empirical treatment that included at least one active antibiotic.

Epidemiology and control measures of an OXA-48-producing Enterobacteriaceae hospital-wide oligoclonal outbreak.

The main objective of our study was to describe the epidemiological and microbiological features of an oligoclonal hospital-wide outbreak caused by OXA-48-producing Enterobacteriaceae (OXA-48-PE). OXA-48 is a carbapenemase belonging to Ambler class D beta-lactamases, identified frequently in the Mediterranean and Southern European countries, and associated with several Enterobacteriaceae species. An outbreak of OXA-48-PE with a complex epidemic pattern was detected in January 2011. Initial control measures included contact precautions and the reinforcement of infection control practices, but despite all efforts made, the epidemiological situation hardly changed and new measures were implemented during 2013. An observational retrospective study was performed to describe the main features of the outbreak and to analyse the cumulative incidence (CI) trends. Eight hundred and 16 patients colonised or infected by OXA-48-PE were identified during the 2-year period (January 2013-December 2014), female 46%, mean age (s.d.), 71.6 (15.2). The samples isolated in the incident cases were rectal swabs (80%), urine samples (10.7%), blood samples (2.8%) and other clinical samples (6.6%). The most frequent OXA-48-PE was Klebsiella pneumoniae. Eleven different clones were identified, but K. pneumoniae sequence types 11 and 405 were predominant: ST11 (64.2%) and ST405 (29.3%). OXA-48-PE CI trend suffered a statistically significant change in August 2013, which continued the following months. Though we could not eradicate the outbreak, we observed a statistically significant drop in CI after an intervention for OXA-48-PE control, based on patient cohort, active surveillance, electronic alerts and reinforcement of infection control measures in a tertiary hospital.

Presence of quinolone resistance to qnrB1 genes and blaOXA-48 carbapenemase in clinical isolates of Klebsiella pneumoniae in Spain.

A study is presented on the presence of quinolone resistance qnrB1 genes in clinical isolates belonging to the largest series of infections caused by OXA-48-producing Klebsiella pneumoniae in a single-centre outbreak in Spain. Evidence is also provided, according to in vitro results, that there is a possibility of co-transfer of plasmid harbouring blaOXA-48 with an other plasmid harbouring qnrB1 in presence of low antibiotic concentrations of fluoroquinolones, showing the risk of multi-resistance screening.

Prevalence of and risk factors for biliary carriage of bacteria showing worrisome and unexpected resistance traits.

Data on biliary carriage of bacteria and, specifically, of bacteria with worrisome and unexpected resistance traits (URB) are lacking. A prospective study (April 2010 to December 2011) was performed that included all patients admitted for <48 h for elective laparoscopic cholecystectomy in a Spanish hospital. Bile samples were cultured and epidemiological/clinical data recorded. Logistic regression models (stepwise) were performed using bactobilia or bactobilia by URB as dependent variables. Models (P < 0.001) showing the highest R(2) values were considered. A total of 198 patients (40.4% males; age, 55.3 ± 17.3 years) were included. Bactobilia was found in 44 of them (22.2%). The presence of bactobilia was associated (R(2) Cox, 0.30) with previous biliary endoscopic retrograde cholangiopancreatography (ERCP) (odds ratio [OR], 8.95; 95% confidence interval [CI], 2.96 to 27.06; P < 0.001), previous admission (OR, 2.82; 95% CI, 1.10 to 7.24; P = 0.031), and age (OR, 1.09 per year; 95% CI, 1.05 to 1.12; P < 0.001). Ten out of the 44 (22.7%) patients with bactobilia carried URB: 1 Escherichia coli isolate (CTX-M), 1 Klebsiella pneumoniae isolate (OXA-48), 3 high-level gentamicin-resistant enterococci, 1 vancomycin-resistant Enterococcus isolate, 3 Enterobacter cloacae strains, and 1 imipenem-resistant Pseudomonas aeruginosa strain. Bactobilia by URB (versus those by non-URB) was only associated (R(2) Cox, 0.19) with previous ERCP (OR, 11.11; 95% CI, 1.98 to 62.47; P = 0.006). For analyses of patients with bactobilia by URB versus the remaining patients, previous ERCP (OR, 35.284; 95% CI, 5.320 to 234.016; P < 0.001), previous intake of antibiotics (OR, 7.200; 95% CI, 0.962 to 53.906; P = 0.050), and age (OR, 1.113 per year of age; 95% CI, 1.028 to 1.206; P = 0.009) were associated with bactobilia by URB (R(2) Cox, 0.19; P < 0.001). Previous antibiotic exposure (in addition to age and previous ERCP) was a risk driver for bactobilia by URB. This may have implications in prophylactic/therapeutic measures.

Opportunities to improve antimicrobial use in paediatric intensive care units: a nationwide survey in Spain.

Improving antimicrobial use is a complex process that requires an accurate assessment of ongoing problems and barriers. Paediatric intensive care units (PICU) have seldom been assessed from this perspective. Two Internet-based, self-administered surveys were conducted nationwide in Spain between January and February 2014. The first survey aimed to assess those characteristics of Spanish PICUs that could influence antimicrobial prescribing or antimicrobial stewardship. The second survey targeted Spanish PICU physicians and pursued to assess their attitudes and perceptions regarding antimicrobial resistance and antimicrobial use. Information about 29/39 contacted PICUs was obtained. A total of 114/206 (55.3%) paediatric intensivists responded. PICUs were heterogeneous regarding years since foundation, number of beds, type of patients admitted and staffing. Only 11 (37.9%) PICUs had available e-prescribing systems. Procalcitonin was available in 24 (89.1%) PICUs, but there were no procalcitonin-based protocols in 14 (60.9%) of them. Half of surveyed PICUs had implemented antimicrobial stewardship activities. Ninety-eight of the 114 PICU physicians (86%) who participated considered that antimicrobial resistance was a significantly relevant problem for their daily and that improving antimicrobial use in their PICU should be a priority (103; 90.4%). The main perceived problems regarding antimicrobial use were the excessive use of antimicrobials in patients with nonconfirmed infections and excessive use of broad-spectrum antimicrobials. The most valued antimicrobial stewardship interventions were the implementation of protocols to guide antimicrobial therapy. Spanish PICU doctors are aware of the relevance of the problem of antimicrobial resistance and the need to improve antimicrobial use. Targeted interventions should take into account their difficulties and preferences when feasible.

Bacteraemia due to OXA-48-carbapenemase-producing Enterobacteriaceae: a major clinical challenge.

Bacteraemia due to carbapenemase-producing Enterobacteriaceae is an emerging medical problem. Management of this entity is complicated by the difficulty in identifying resistance patterns and the limited therapeutic options. A cohort study was performed including all episodes of bloodstream infection due to OXA-48-producing Enterobacteriaceae (O48PE), occurring between July 2010 and April 2012. Data on predisposing factors, clinical presentation, therapy and outcome were collected from medical records. There were 40 cases of bacteraemia caused by O48PE, 35 Klebsiella pneumoniae and five Escherichia coli. Patients were elderly with significant comorbidities (57.5% underlying malignancy). Thirty-five cases (87.5%) were nosocomial, and five (12.5%) were healthcare-associated. Patients had frequently been exposed to antibiotics and to invasive procedures during hospitalization. The most common source of bacteraemia was the urinary tract followed by deep intra-abdominal surgical site infection. Clinical presentation was severe sepsis or shock in 18 cases (45%). Extended-spectrum ß-lactamase production was detected in 92.5% of isolates. MIC(90) for ertapenem, imipenem and meropenem were 32, 16 and 16 mg/L, respectively. Most frequently preserved antibiotics were amikacin, colistin, tigecycline and fosfomycin. These antibiotics combined are the basis of targeted therapies, including carbapenem in selected cases. Median delay in starting clinically adequate and microbiologically appropriate treatment was 3 days. Crude mortality during admission and within 30 days from bacteraemia was 65% and 50%, respectively. Bloodstream infections caused by O48PE have a poor prognosis. Delay in diagnosis and in initiation of optimal antimicrobial therapy is frequent. Suspicion and rapid identification could contribute to improving outcomes.

Detection and characterization of Enterobacteriaceae producing metallo-beta-lactamases in a tertiary-care hospital in Spain.

Carbapenem-resistant or intermediate (MIC >or=1 mg/L) clinical isolates (n = 12) of three species of Enterobacteriaceae (Klebsiella pneumoniae, Klebsiella oxytoca and Escherichia coli) were characterized. The isolates harboured integrons containing the VIM-1 metallo-beta-lactamase gene together with other resistance gene cassettes. In particular, the CTX-M-2 gene was detected in four of the K. pneumoniae isolates. The patient population was mostly paediatric and characterized by severe underlying illnesses that involved long-term hospitalization, major surgery and/or immunosuppressive and broad-spectrum antibiotic therapy.

[Vasculitis associated with anti-neutrophil cytoplasmic autoantibodies in rheumatoid arthritis. Report of a case of microscopic polyangiitis and another case of Wegener's granulomatosis]. / Vasculitis asociadas a ANCA en artritis reumatoide. Descripción de un caso de poliangeitis microscópica y otro de enfermedad de Wegener.

Vasculitis is an uncommon complication of rheumatoid arthritis that is associated with a clear increase in morbidity and mortality, although systemic manifestations such as glomerulonephritis, cerebral vasculitis or pulmonary vasculitis are very rare. Systemic vasculitis with renal involvement is associated with overt polyarthritis in less than 5% and association with rheumatoid arthritis is exceptional. Determination of anti-neutrophil cytoplasmic autoantibodies (ANCA), used in the appropriate clinical context, has become an important diagnostic tool in small-vessel systemic vasculitides. We present two patients with rheumatoid arthritis who subsequently developed systemic vasculitis. ANCA determination was decisive in the early diagnosis of these patients.

Vasculitis asociadas a ANCA en artritis reumatoide. Descripción de un caso de poliangeitis microscópica y otro de enfermedad de Wegener / Vasculitis associated with anti-neutrophil cytoplasmic autoantibodies in rheumatoid arthritis. Report of a case of microscopic polyangiitis and another case of Wegener’s granulomatosis

La vasculitis es una complicación infrecuente de la artritis reumatoide que se asocia con un aumento claro de la morbimortalidad, aunque son muy raras las manifestaciones sistémicas como glomerulonefritis, vasculitis cerebral o vasculitis pulmonar. A su vez, las vasculitis sistémicas con afectación renal se asocian en menos del 5% a poliartritis franca y la asociación con artritis reumatoide es excepcional. La determinación de los anticuerpos anticitoplasma de neutrófilo (ANCA), utilizados en el contexto clínico apropiado, se ha convertido en una importante herramienta diagnóstica de las vasculitis sistémicas de pequeño vaso. Presentamos 2 pacientes diagnosticados de artritis reumatoide que posteriormente desarrollaron vasculitis sistémica, en los que la determinación de ANCA fue decisiva en el diagnóstico precoz(AU)

Vasculitis is an uncommon complication of rheumatoid arthritis that is associated with a clear increase in morbidity and mortality, although systemic manifestations such as glomerulonephritis, cerebral vasculitis or pulmonary vasculitis are very rare. Systemic vasculitis with renal involvement is associated with overt polyarthritis in less than 5% and association with rheumatoid arthritis is exceptional. Determination of anti-neutrophil cytoplasmic autoantibodies (ANCA), used in the appropriate clinical context, has become an important diagnostic tool in small-vessel systemic vasculitides. We present two patients with rheumatoid arthritis who subsequently developed systemic vasculitis. ANCA determination was decisive in the early diagnosis of these patients(AU)