Publications by authors named "José Antonio Martinez"

107 Publications

Impact of Inflammatory Response Modifiers on the Incidence of Hospital-Acquired Infections in Patients with COVID-19.

Infect Dis Ther 2021 Jun 11. Epub 2021 Jun 11.

Department of Infectious Diseases, Hospital Clinic of Barcelona, C/ Villarroel 170, 08036, Barcelona, Spain.

Introduction: The study aim was to assess the influence of inflammatory response modifiers, including anti-interleukin-6 (IL-6) biologics and corticosteroids, on the incidence of hospital-acquired infections in patients with coronavirus disease 2019 (COVID-19).

Methods: Case-control study performed at a university hospital from February 26 to May 26, 2020. Cases were defined as patients with COVID-19 who developed hospital-acquired infections. For each case, two controls were selected among patients without infections. Cases and controls were matched obeying three criteria in a hierarchical sequence: length of hospital stay up until the first infection; comorbidity; and need for Intensive care unit (ICU) admission. Conditional logistic regression analysis was used to estimate the association of exposures with being a case.

Results: A total of 71 cases and 142 controls were included. Independent predictors for acquiring a hospital infection were chronic liver disease [odds ratio (OR) 16.56, 95% CI 1.87-146.5, p = 0.012], morbid obesity (OR 6.11, 95% CI 1.06-35.4, p = 0.043), current or past smoking (OR 4.15, 95% CI 1.45-11.88, p = 0.008), exposure to hydroxychloroquine (OR 0.2, 95% CI 0.041-1, p = 0.053), and invasive mechanical ventilation (OR 61.5, 95% CI 11.08-341, p ≤ 0.0001).

Conclusions: Inflammatory response modifiers had no influence on acquisition of nosocomial infections in admitted patients with COVID-19. Hospital-acquired infections primarily occurred in the critically ill and invasive mechanical ventilation was the main exposure conferring risk.
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http://dx.doi.org/10.1007/s40121-021-00477-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193595PMC
June 2021

Changing epidemiology of catheter-related bloodstream infections in neutropenic oncohematological patients.

PLoS One 2021 30;16(4):e0251010. Epub 2021 Apr 30.

Infectious Diseases Department, Hospital Clínic-IDIBAPS, Barcelona, Spain.

Background: We aimed to describe the epidemiology of catheter-related bloodstream infections (CRBSIs) in onco-hematological neutropenic patients during a 25-year study period, to evaluate the risk factors for Gram-negative bacilli (GNB) CRBSI, as well as rates of inappropriate empirical antibiotic treatments (IEAT) and mortality.

Materials/methods: All consecutive episodes of CRBSIs were prospectively collected (1994-2018). Changing epidemiology was evaluated comparing five-year time spans. A multivariate regression model was built to evaluate risk factors for GNB CRBSIs.

Results: 482 monomicrobial CRBSIs were documented. The proportion of CRBSIs among all BSIs decreased over time from 41.2% to 15.8% (p<0.001). CRBSIs epidemiology has been changing: the rate of GNB increased over time (from 11.9% to 29.4%; p<0.001), as well as the absolute number and rate of multidrug-resistant (MDR) GNB (from 9.5% to 40.0%; p = 0.039). P. aeruginosa increased and comprised up to 40% of all GNB. Independent factors related with GNB-CRBSIs were: longer duration of in-situ catheter (OR 1.007; 95%CI 1.004-1.011), older age (OR 1.016; 95%CI 1.001-1.033), prior antibiotic treatment with penicillins (OR 2.716; 95%CI 1.306-5.403), and current antibiotic treatment with glycopeptides (OR 1.931; 95%CI 1.001-3.306). IEATs were administered to 30.7% of patients, with the highest percentage among MDR P. aeruginosa (76.9%) and S. maltophillia (92.9%). Mortality rate was greater among GNB than GPC-CRBSI (14.4% vs 5.4%; p = 0.002), with mortality increasing over time (from 4.5% to 11.2%; p = 0.003).

Conclusion: A significant shift towards GNB-CRBSIs was observed. Secondarily, and coinciding with an increasing number of GNB-MDR infections, mortality increased over time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251010PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087001PMC
April 2021

Trends in mortality of hospitalised COVID-19 patients: A single centre observational cohort study from Spain.

Lancet Reg Health Eur 2021 Apr 24;3:100041. Epub 2021 Jan 24.

Department of Infectious Diseases, Hospital Clinic of Barcelona-IDIBAPS, University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain.

Background: We aimed to describe changes in characteristics and treatment strategies of hospitalised patients with COVID-19 and detail the mortality trend over time.

Methods: Observational cohort study of all consecutive patients admitted ≥ 48 h to Hospital Clinic of Barcelona for COVID-19 (1 March-30 September 2020).

Findings: A total of 1645 consecutive patients with COVID-19 were assessed over a 7-month period. Overall mortality (≤30 days) was 9.7% (159 patients), 7.7% in patients hospitalised in regular wards and 16.7 % in patients requiring ICU admission. Overall mortality decreased from 11.6% in the first month to 1.4% in the last month, reflecting a progressive, significant downward trend ( for trend <0.001). Patients' age changed over time, peaking in June. Most changes in the use of antivirals and anti-inflammatory treatments were documented. Age (OR 1.1, CI 1.1-1.12), chronic heart disease, (OR 1.7, CI 1.1-2.9), D-dimer>700 ng/mL (OR 2.3, CI 1.3-4.1), ferritin>489 ng/mL (OR 1.9; CI 1.5-3.2), C-RP>7 mg/dL (OR 2.6; CI 1.5-4.6), and shorter duration from symptom onset to hospital admission (OR 1.11; CI 1.04-1.17) were factors associated with 30-day mortality at hospital admission. Conversely, hospital admission in the last months (OR 0.80; CI 0.65-0.98) was significantly associated with lower mortality.

Interpretation: In-hospital mortality has decreased in patients with COVID-19 over the last, few months, even though main patient characteristics remain similar. Several changes made when managing patients may explain this decreasing trend. Our study provides current data on mortality of patients hospitalised with COVID-19 that might be useful in establishing quality of standard of care.

Funding: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme), EDRD. PPA [CM18/00132], NGP [FI19/00133], and CGV [FIS PI18/01061], have received grants from Ministerio de Sanidad y Consumo, ISCIII.
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http://dx.doi.org/10.1016/j.lanepe.2021.100041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830193PMC
April 2021

Factors Associated With Short-Term Eradication of Rectal Colonization by KPC-2 Producing in an Outbreak Setting.

Front Microbiol 2021 1;12:630826. Epub 2021 Feb 1.

Service of Infectious Diseases, Hospital Clínic de Barcelona, Barcelona, Spain.

KPC-producing (KPCKP) is a threat for patients admitted to healthcare institutions. To assess the efficacy of several decolonization strategies for KPCKP rectal carriage. Observational study performed in a 750-bed university center from July to October 2018 on the efficacy of a 10-day non-absorbable oral antibiotic (NAA) regimen (colistin 10 mg/ml, amikacin 8 mg/ml, and nystatin 30 mg/ml, 10 ml/6 h) vs. the same regimen followed by a probiotic (Vivomixx®) for 20 days in adult patients with KPCKP rectal colonization acquired during an outbreak. Seventy-three patients colonized by KPCKP were included, of which 21 (29%) did not receive any treatment and 52 (71.2%) received NAA either alone ( = 26, 35.6%) or followed by a probiotic ( = 26, 35.6%). Eradication was observed in 56 (76.7%) patients and the only variable significantly associated with it was not receiving systemic antibiotics after diagnosis of rectal carriage [22/24 (91.6%) vs. 34/49 (69.3%), = 0.04]. Eradication in patients receiving NAA plus probiotic was numerically but not significantly higher than that of controls [23/26 (88.4%) vs. 15/21 (71.4%), = 0.14] and of those receiving only NAA (OR = 3.4, 95% CI = 0.78-14.7, = 0.09). In an outbreak setting, rectal carriage of KPCKP persisted after a mean of 36 days in about one quarter of patients. The only factor associated with eradication was not receiving systemic antibiotic after diagnosis. A 10-day course of NAA had no impact on eradication. Probiotics after NAA may increase the decolonization rate, hence deserving further study.
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http://dx.doi.org/10.3389/fmicb.2021.630826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882481PMC
February 2021

Management of perianal fistula in inflammatory bowel disease: identification of prognostic factors associated with surgery.

Langenbecks Arch Surg 2021 Jun 30;406(4):1181-1188. Epub 2021 Jan 30.

General Surgery Department, La Paz University Hospital, Paseo de la Castellana, 261 28046, Madrid, Spain.

Purpose: As one of the clinical manifestations of inflammatory bowel disease (IBD), perianal fistula disease (PFD) can potentially impact the patient quality of life. The management of PFD employs a multidisciplinary approach which includes antibiotics, biological therapies, immunomodulators, and surgery. We analyzed the outcome and prognostic factors of anal fistula surgery in IBD patients.

Methods: We conducted a retrospective study of IBD patients undergoing elective surgery for anal fistula between January 2015 and December 2018 at our University Department of Surgery. We collated demographic factors, disease activity, imaging (MRI and endoanal ultrasound), surgical interventions, and medical treatment assessing the rate of fistula closure and fecal incontinence, 2 months and 1 year after surgery.

Results: Thirty-five IBD patients with anal fistula underwent surgery (28 Crohn's disease, four ulcerative colitis, and three indeterminate colitis). Twenty-seven patients presented with complex fistulas and eight with simple fistulas with 10 patients undergoing single-stage surgery. In 25 patients, a two-stage surgical approach was planned and performed (draining seton plus medical treatment and then second-stage surgery with curative intent). At 1 year of follow-up, the fistula healing rate was 50% for single-stage surgery and 60% for two-stage surgery (P = 0.09). Overall, 19.2% of patients developed postoperative fecal incontinence. A time interval greater than 12 months between surgeries is a favorable prognostic factor for fistula healing with the two-stage approach (P = 0.002).

Conclusions: In our retrospective study, two-stage surgery in IBD patients presenting with complex perianal fistulous disease results in a better medium-term outcome with a longer time interval between surgeries.
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http://dx.doi.org/10.1007/s00423-021-02100-4DOI Listing
June 2021

Dissemination of NDM-producing Klebsiella pneumoniae and Escherichia coli high-risk clones in Catalan healthcare institutions.

J Antimicrob Chemother 2021 01;76(2):345-354

Laboratory of Antimicrobial Resistance, ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.

Objectives: To characterize the clonal spread of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates between different healthcare institutions in Catalonia, Spain.

Methods: Antimicrobial susceptibility was tested by disc diffusion. MICs were determined by gradient diffusion or broth microdilution. Carbapenemase production was confirmed by lateral flow. PCR and Sanger sequencing were used to identify the allelic variants of resistance genes. Clonality studies were performed by PFGE and MLST. Plasmid typing, conjugation assays, S1-PFGE plus Southern blotting and MinION Oxford Nanopore sequencing were used to characterize resistance plasmids.

Results: Twenty-nine carbapenem-resistant isolates recovered from three healthcare institutions between January and November 2016 were included: 14 K. pneumoniae isolates from a tertiary hospital in the south of Catalonia (hospital A); 2 K. pneumoniae isolates from a nearby healthcare centre; and 12 K. pneumoniae isolates and 1 E. coli isolate from a tertiary hospital in Barcelona (hospital B). The majority of isolates were resistant to all antimicrobial agents, except colistin, and all were NDM producers. PFGE identified a major K. pneumoniae clone (n = 27) belonging to ST147 and co-producing NDM-1 and CTX-M-15, with a few isolates also harbouring blaOXA-48. Two sporadic isolates of K. pneumoniae ST307 and E. coli ST167 producing NDM-7 were also identified. blaNDM-1 was carried in two related IncR plasmid populations and blaNDM-7 in a conjugative 50 kb IncX3 plasmid.

Conclusions: We report the inter-hospital dissemination of XDR high-risk clones of K. pneumoniae and E. coli associated with the carriage of small, transferable plasmids harbouring blaNDM genes.
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http://dx.doi.org/10.1093/jac/dkaa459DOI Listing
January 2021

Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection.

Crit Care Med 2020 12;48(12):e1350-e1355

Apheresis Unit, Hemotherapy and Hemostasis Department, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain.

Objectives: Infection by severe acute respiratory syndrome coronavirus-2 can induce uncontrolled systemic inflammation and multiple organ failure. The aim of this study was to evaluate if plasma exchange, through the removal of circulating mediators, can be used as rescue therapy in these patients.

Design: Single center case series.

Setting: Local study.

Subjects: Four critically ill adults with coronavirus disease 19 pneumonia that failed conventional interventions.

Interventions: Plasma exchange. Two to six sessions (1.2 plasma volumes). Human albumin (5%) was used as the main replacement fluid. Fresh frozen plasma and immunoglobulins were administered after each session to avoid coagulopathy and hypogammaglobulinemia.

Measurements And Main Results: Serum markers of inflammation and macrophage activation. All patients showed a dramatic reduction in inflammatory markers, including the main cytokines, and improved severity scores after plasma exchange. All survived to ICU admission.

Conclusions: Plasma exchange mitigates cytokine storm, reverses organ failure, and could improve survival in critically ill patients with coronavirus disease 2019 infection.
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http://dx.doi.org/10.1097/CCM.0000000000004613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493773PMC
December 2020

Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study.

Clin Microbiol Infect 2021 Jan 31;27(1):83-88. Epub 2020 Jul 31.

Department of Infectious Diseases, Hospital Clinic of Barcelona, IDIBAPS, Barcelona, Spain.

Objectives: To describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19).

Methods: We performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records.

Results: Of a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes.

Conclusions: Co-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies.
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http://dx.doi.org/10.1016/j.cmi.2020.07.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836762PMC
January 2021

Personalized therapy approach for hospitalized patients with COVID-19.

Clin Infect Dis 2020 Jul 10. Epub 2020 Jul 10.

Department of Infectious Diseases, Hospital Clinic of Barcelona, Barcelona, Spain.

Hospitalized patients with COVID-19 experiencing respiratory symptoms have different complications (inflammatory, co-infection and thrombotic) that are identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (OR 0.144, CI 0.03-0.686; p=0.015). Increasing age (OR 1.06; p=0.038) and therapeutic effort limitation (OR 9.684; p<0.001) were associated with higher mortality.
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http://dx.doi.org/10.1093/cid/ciaa964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454444PMC
July 2020

Higher MICs (>2 mg/L) Predict 30-Day Mortality in Patients With Lower Respiratory Tract Infections Caused by Multidrug- and Extensively Drug-Resistant Treated With Ceftolozane/Tazobactam.

Open Forum Infect Dis 2019 Oct 28;6(10):ofz416. Epub 2019 Sep 28.

Servicio de Enfermedades Infecciosas, Hospital Clínic, Barcelona, Spain.

Background: Ceftolozane/tazobactam (C/T) efficacy and safety in ventilator-associated pneumonia (VAP) is being evaluated at a double dose by several trials. This dosing is based on a pharmacokinetic (PK) model that demonstrated that 3 g q8h achieved ≥90% probability of target attainment (50% ƒT > minimal inhibitory concentration [MIC]) in plasma and epithelial lining fluid against C/T-susceptible . The aim of this study was to evaluate the efficacy of different C/T doses in patients with lower respiratory infection (LRI) due to MDR- or XDR- considering the C/T MIC.

Methods: This was a multicenter retrospective study of 90 patients with LRI caused by resistant who received a standard or high dose (HDo) of C/T. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality.

Results: The median age (interquartile range) was 65 (51-74) years. Sixty-three (70%) patients had pneumonia, and 27 (30%) had tracheobronchitis. Thirty-three (36.7%) were ventilator-associated respiratory infections. The median C/T MIC (range) was 2 (0.5-4) mg/L. Fifty-four (60%) patients received HDo. Thirty-day mortality was 27.8% (25/90). Mortality was significantly lower in patients with strains with MIC ≤2 mg/L and receiving HDo compared with the groups with the same or higher MIC and dosage (16.2% vs 35.8%; = .041). Multivariate analysis identified septic shock ( < .001), C/T MIC >2 mg/L ( = .045), and increasing Charlson Comorbidity Index ( = .019) as independent predictors of mortality.

Conclusions: The effectiveness of C/T in LRI was associated with an MIC ≤2 mg/L, and the lowest mortality was observed when HDo was administered for strains with C/T MIC ≤2 mg/L. HDo was not statistically associated with a better outcome.
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http://dx.doi.org/10.1093/ofid/ofz416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810667PMC
October 2019

Acute liver failure due to visceral leishmaniasis in Barcelona: a case report.

BMC Infect Dis 2019 Oct 22;19(1):874. Epub 2019 Oct 22.

Infectious Diseases Service Hospital Clinic-IDIBAPS, Villarroel 170, 08032, Barcelona, Spain.

Background: Leishmaniasis is an emerging infectious disease. Due to human migration and tourism, visceral leishmaniasis may become more common in non-endemic areas. In the Mediterranean basin, visceral leishmaniasis typically occurs in rural regions.

Case Presentation: We present an unusual urban case of acute liver failure due to visceral leishmaniasis, following a prolonged fever of unknown origin. After obtaining negative results from the bone marrow aspirate, we performed a liver biopsy that elucidated the diagnosis. The liver involvement in visceral leishmaniasis may appear as chronic granulomatous hepatitis. However diffuse hepatitis process, a necro-inflammatory pattern, without forming granulomas were observed in the liver biopsy specimens in this case. Intracytoplasmic Leishmania amastigotes were observed in the liver biopsy specimens and a polymerase chain reaction confirmed the diagnosis. Only five pathological confirmed cases of acute hepatitis due to visceral leishmaniasis have been described so far, just two in adults and both from Barcelona. A revision of the literature is performed.

Conclusions: Acute hepatitis is an uncommon debut of visceral leishmaniasis in immunocompetent patients. Furthermore there are only few cases in the literature that describe the histopathological changes that we found in this patient. In conclusion, in case of acute hepatitis leading to liver failure, leishmaniasis should be considered a differential diagnosis (even in non-endemic countries and without clear epidemiological exposure) and liver biopsy can elucidate the diagnosis.
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http://dx.doi.org/10.1186/s12879-019-4553-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805620PMC
October 2019

Changing epidemiology of bloodstream infection in a 25-years hematopoietic stem cell transplant program: current challenges and pitfalls on empiric antibiotic treatment impacting outcomes.

Bone Marrow Transplant 2020 03 30;55(3):603-612. Epub 2019 Sep 30.

Infectious Diseases Department, Hospital Clínic-IDIBAPS, Barcelona, Spain.

We aimed to describe epidemiology changes in bloodstream infections (BSI) episodes in hematopoietic stem cell transplant (HSCT) recipients throughout a 25-year period (1993-2017), comparing five-year time spans, and we evaluate their impact on inappropriate empirical antibiotic treatment (IEAT) and mortality. During the study period, 1164 BSI episodes were documented in patients undergoing HSCT (71.6% allogenic and 29% autologous). A significant decrease in gram-positive cocci (GPC) and increase in gram-negative bacilli (GNB) were observed (p < 0.001). Among GP, coagulase-negative staphylococci (CoNS) significantly decreased whereas rising E. faecium BSI was documented. Among GNB, E. coli, Pseudomonas aeruginosa and K. pneumoniae rates increased. Multidrug-resistant (MDR) GNB, especially ESBL-E. coli and MDR-P. aeruginosa, emerged in 2008 and has gradually increased. IEAT against MDR-P. aeruginosa, but not in other MDR-GNB, augmented throughout the study period. Overall, 30-day and related mortality rates were 12.7% and 7.7% respectively, both increasing over time (p < 0.001 and p = 0.025). In GNB, 30-day and related mortality were 18.5% and 12.8%, respectively, increasing over time (p < 0.001 and p = 0.004). To conclude, important BSI epidemiological changes were described in a 25-year period. Concerning increase in IEAT for P. aeruginosa infections and rising 30-day mortality rate were documented.
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http://dx.doi.org/10.1038/s41409-019-0701-3DOI Listing
March 2020

Inappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug Resistance.

Clin Infect Dis 2020 03;70(6):1068-1074

Infectious Diseases Department, Hospital Clínic-Institut d'investigacions Biomèdiques August Pi i Sunyer.

Background: We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality.

Methods: This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006-2017). Episodes receiving IEAT were compared with episodes receiving appropriate empirical therapy. Adherence to Infectious Diseases Society of America (IDSA) recommendations was evaluated. Multivariate analysis was performed to identify independent risk factors for mortality in Pseudomonas aeruginosa episodes.

Results: Of 1615 episodes, including Escherichia coli (24%), coagulase-negative staphylococci (21%), and P. aeruginosa (16%), 394 (24%) received IEAT despite IDSA recommendations being followed in 87% of cases. Patients with multidrug-resistant gram-negative bacilli (MDR-GNB), accounting for 221 (14%) of all isolates, were more likely to receive IEAT (39% vs 7%, P < .001). Overall mortality was higher in patients with GNB BSI who received IEAT (36% vs 24%, P = .004); when considering individual microorganisms, only patients with infection caused by P. aeruginosa experienced a significant increase in mortality when receiving IEAT (48% vs 31%, P = .027). Independent risk factors for mortality in PA BSI (odds ratio [95% confidence interval] were IEAT (2.41 [1.19-4.91]), shock at onset (4.62 [2.49-8.56]), and pneumonia (3.01 [1.55-5.83]).

Conclusions: IEAT is frequent in high-risk patients with FN and BSI, despite high adherence to guidelines. This inappropriate treatment primarily impacts patients with P. aeruginosa-related BSI mortality and in turn is the only modifiable factor to improve outcomes.
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http://dx.doi.org/10.1093/cid/ciz319DOI Listing
March 2020

Clinical characteristics and prognosis of infections caused by OXA-48 carbapenemase-producing Enterobacteriaceae in patients treated with ceftazidime-avibactam.

Int J Antimicrob Agents 2019 Apr 22;53(4):520-524. Epub 2018 Nov 22.

Department of Infectious Diseases, Hospital Clinic, Barcelona, University of Barcelona, IDIBAPS, Spain.

Background: Ceftazidime-avibactam has in vitro activity against Gram-negative bacilli that produce Class A, C and some D β-lactamases, and has been successfully used in the treatment of infections caused by cephalosporin and carbapenem-resistant Enterobacteriaceae. However, actual experience in the treatment of OXA-48 carbapenemase-producing Enterobacteriaceae (CPE) is limited.

Objective: To review the characteristics and prognosis of OXA-48 CPE infections treated with ceftazidime-avibactam since introduction of the drug to the current centre during the period October 2014 to December 2016.

Methods: Retrospective assessment of episodes of infection caused by OXA-48 CPE treated with ceftazidime-avibactam, analysing data collected from infection diagnosis until 90 days after the end of treatment.

Results: Twenty-four episodes were analysed. Ceftazidime-avibactam was given as the initial definitive treatment in 15 (62.5%) and as salvage therapy in nine (37.5%). Intraabdominal (seven, 29%), urinary (six, 25%) and respiratory (five, 21%) were the most common sources. The 30-day and 90-day mortality rates were 8.3% and 20.8%, respectively. Clinical cure at 30 days was achieved in 62.5% of episodes. Four (16.7%) patients had adverse events, two of them were related to impaired renal function. Among patients who finished the treatment with ceftazidime-avibactam, seven (35%) were diagnosed with infection recurrence within 90 days of the end of treatment.

Conclusions: From experience, ceftazidime-avibactam is an effective drug for treating infections due to OXA-48 CPE. From these results a better safety profile than the current best available therapy could be expected.
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http://dx.doi.org/10.1016/j.ijantimicag.2018.11.015DOI Listing
April 2019

Antituberculous Treatment Itself Might Prevent Visual Impairment in Presumed Tuberculosis-Related Uveitis.

Ocul Immunol Inflamm 2020 5;28(1):103-110. Epub 2018 Nov 5.

Clínic Institute of Ophthalmology (ICOF), Clínic Hospital of Barcelona, Barcelona, Spain.

: To study the risk factors for visual loss in presumed tuberculosis-related uveitis (TRU).: Retrospective observational cohort study of patients with TRU, either treated or not for tuberculosis, from January 2005 to January 2017. Clinical and demographic variables were recorded. Main outcome measure was a loss of visual acuity (VA) of ≥2 Snellen lines. A Generalized Estimation Equation was used to control between-eyes bias. A backward stepwise logistic regression multivariate analysis was conducted to elucidate independent risk factors.: One hundred and thirty-eight eyes from 82 patients were included. There were 45 males, median age at onset of uveitis was 40 years (Interquartile range, IQR 24). The median follow-up was 36 months (IQR 49.75) and 51 patients completed antituberculous treatment (ATT) for a mean of 9.37 months. In the multivariate model, ATT was the only independent protective factor for loss of VA (OR 0.13, 95% CI 0.04-0.37,  < 0.001).: ATT itself may prevent visual loss in TRU.
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http://dx.doi.org/10.1080/09273948.2018.1541326DOI Listing
December 2020

Short-Term Peripheral Venous Catheter-Related Bloodstream Infections: Evidence for Increasing Prevalence of Gram-Negative Microorganisms from a 25-Year Prospective Observational Study.

Antimicrob Agents Chemother 2018 11 24;62(11). Epub 2018 Oct 24.

Service of Infectious Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain

The aim of this study was to describe the etiology and outcome of short-term peripheral venous catheter (PVC)-related bloodstream infections (PVCRBSI) in a 25-year period (1992 to 2016) and to identify predictive factors of Gram-negative PVCRBSI. This was a prospective observational study including all episodes of PVCRBSI. A multivariate logistic regression model adjusted for calendar year was built to explore factors associated with a Gram-negative bacterial etiology. Over the study period, 711 episodes of PVCRBSI were identified. Incidence rate of PVCRBSI increased from 0.06 to 0.13 episodes/1,000 patient-days. A Gram-negative bacterial etiology was demonstrated in 162 (22.8%) episodes. There was a significant increase in the proportion of Gram-negative infections (22.6% in 1992 to 1996 versus 33.2% in 2012 to 2016). Independent predictive factors of Gram-negative PVCRBSI were the following: being in the hospital for more than 7 days with a catheter for more than 3 days (adjusted odds ratio [aOR], 1.80; 95% confidence interval [CI], 1.20 to 2.69), surgery in the previous month (aOR, 2.39; 95% CI, 1.40 to 4.09), and antimicrobial treatment with beta-lactams (aOR, 1.80; 95% CI, 1.16 to 2.78). In conclusion, we reported an increase in the prevalence of Gram-negative PVCRBSI over the last 25 years. Factors associated with a Gram-negative bacterial etiology were being in the hospital for more than 7 days with a catheter for more than 3 days, having undergone surgery, and having received antimicrobial treatment with beta-lactams.
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http://dx.doi.org/10.1128/AAC.00892-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201066PMC
November 2018

Laparoscopic surgical transmesocolic jejunostomy: A new surgical approach.

Turk J Surg 2018 3;34(2):155-157. Epub 2018 Jan 3.

Department of General Surgery, Hospital Universitario Son Espases, Palma De Mallorca, Spain.

In cancer patients with tumors of the upper gastrointestinal tract, dysphagia and cachexia require gastrostomy or jejunostomy as the only options for enteral access for long-term feeding. In this article, the authors describe a modified placement of laparoscopic feeding jejunostomy applied during laparoscopic oncology layering technique. After performing an exploratory laparoscopy, a feeding jejunostomy is performed using a Foley silicon catheter, through an eyelet in the mesentery of the descending colon. After completing the introduction of the jejunal probe according to the Witzel technique, the intestinal segment of jejunum is attached to the internal sheath of the mesocolon using sutures polysorb 2/0, with the aim of removing the possible internal hernia and a jejunal torque that could cause an intestinal obstruction. There were no intraoperative complications or mortality. The technique described here provides most of the benefits of laparoscopic jejunostomy feeding, avoiding the possible internal hernia.
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http://dx.doi.org/10.5152/turkjsurg.2017.3211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048648PMC
January 2018

Risk factors for mortality in patients with acute leukemia and bloodstream infections in the era of multiresistance.

PLoS One 2018 28;13(6):e0199531. Epub 2018 Jun 28.

Infectious Diseases Department, Hospital Clínic-IDIBAPS, Barcelona, Spain.

Objectives: We assess the epidemiology and risk factors for mortality of bloodstream infection (BSI) in patients with acute leukemia (AL).

Methods: Prospectively collected data of a cohort study from July 2004 to February 2016. Multivariate analyses were performed.

Results: 589 episodes of BSI were documented in 357 AL patients, 55% caused by gram-positive bacteria (coagulase-negative staphylococci 35.7%, Enterococcus spp 10.8%) and 43.5% by gram-negative bacteria (E. coli 21%, PA 12%). We identified 110 (18.7%) multidrug-resistant (MDR) microorganisms, especially MDR-Pseudomonas aeruginosa (7%) and extended-spectrum beta-lactamase producing Enterobacteriaceae (7%). The 30-day mortality was 14.8%. Age (OR 3.1; 95% CI 1.7-5.7); chronic lung disease (4.8; 1.1-21.8); fatal prognosis according to McCabe index (13.9; 6.4-30.3); shock (3.8; 1.9-7.7); pulmonary infection (3.6; 1.3-9.9); and MDR-PA infections with inappropriate treatment (12.8; 4.1-40.5) were related to mortality. MDR-PA BSI was associated to prior antipseudomonal cephalosporin use (9.31; 4.38-19.79); current use of betalactams (2.01; 1.01-4.3); shock (2.63; 1.03-6.7) and pulmonary source of infection (9.6; 3.4-27.21).

Conclusions: MDR organisms were commonly isolated in BSI in AL. Inappropriate empiric antibiotic treatment for MDR-PA is the primary factor related to mortality that can be changed. New treatment strategies to improve the coverage of MDR-PA BSI should be considered in those patients with risk factors for this infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199531PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023133PMC
December 2018

Effect of Fruits and Soybean Oil on Finishing Lamb Performance and Meat Characteristics.

Biomed Res Int 2018 21;2018:9486258. Epub 2018 Feb 21.

CIACYT, Universidad Autónoma de San Luis Potosí, 78000 San Luis Potosí, SLP, Mexico.

To evaluate phenolic compounds and whether the combination of a tanniferous fruit and soybean oil could improve the performance, meat characteristics, and fatty acid (FA) profile in lambs, an experiment was conducted over 40 days with twenty creole male lambs (23.71 ± 3.46 kg). The lambs were allotted in a completely randomised design, with factorial arrangement 2 × 2, with the following dietary treatments: (1) control diet, (2) 2% ground fruit dry matter (DM), (3) 2% soybean oil DM, and (4) 2% fruit plus 2% soybean oil. The concentration of condensed tannins (CT) in was 21.71 g/kg DM. No interactions were detected ( > 0.05) among soybean oil and , and there were no differences in daily gain, intake, and feed conversion. Soybean oil reduced ( < 0.05) DM digestibility (68.05 versus 59.56%). In fat from the (LTL) muscle, only linoleic acid presented differences ( < 0.05) between treatments. The combination of fruit and soybean oil did not improve lamb performance at the included levels.
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http://dx.doi.org/10.1155/2018/9486258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841064PMC
September 2018

Influence of empirical double-active combination antimicrobial therapy compared with active monotherapy on mortality in patients with septic shock: a propensity score-adjusted and matched analysis.

J Antimicrob Chemother 2017 Dec;72(12):3443-3452

Hospital Clínic de Barcelona, Service of Infectious Diseases, Carrer de Villarroel, 170, 08036 Barcelona, Spain.

Objectives: To evaluate the influence on mortality of empirical double-active combination antimicrobial therapy (DACT) compared with active monotherapy (AM) in septic shock patients.

Methods: A retrospective study was performed of monomicrobial septic shock patients admitted to a university centre during 2010-15. A propensity score (PS) was calculated using a logistic regression model taking the assigned therapy as the dependent variable, and used as a covariate in multivariate analysis predicting 7, 15 and 30 day mortality and for matching patients who received DACT or AM. Multivariate models comprising the assigned therapy group and the PS were built for specific patient subgroups.

Results: Five-hundred and seventy-six patients with monomicrobial septic shock who received active empirical antimicrobial therapy were included. Of these, 340 received AM and 236 DACT. No difference in 7, 15 and 30 day all-cause mortality was found between groups either in the PS-adjusted multivariate logistic regression analysis or in the PS-matched cohorts. However, in patients with neutropenia, DACT was independently associated with a better outcome at 15 (OR 0.29, 95% CI 0.09-0.92) and 30 (OR 0.25, 95% CI 0.08-0.79) days, while in patients with Pseudomonas aeruginosa infection DACT was associated with lower 7 (OR 0.12, 95% CI 0.02-0.7) and 30 day (OR 0.26, 95% CI 0.08-0.92) mortality.

Conclusions: All-cause mortality at 7, 15 and 30 days was similar in patients with monomicrobial septic shock receiving empirical double-active combination therapy and active monotherapy. However, a beneficial influence of empirical double-active combination on mortality in patients with neutropenia and those with P. aeruginosa infection is worthy of further study.
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http://dx.doi.org/10.1093/jac/dkx315DOI Listing
December 2017

Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosa Isolates from Spain.

Antimicrob Agents Chemother 2017 11 24;61(11). Epub 2017 Oct 24.

Department of Microbiology, Intensive Care Unit and Unidad de Investigación, Hospital Universitari Son Espases, Instituto de Investigación Illes Balears (IdISBa), Palma de Mallorca, Spain

This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) clinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis-multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% ( = 101) of the XDR isolates, distantly followed by ST244 ( = 16), ST253 ( = 12), ST235 ( = 8), and ST111 ( = 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital ( = 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the β-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in β-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.
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http://dx.doi.org/10.1128/AAC.01589-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655108PMC
November 2017

Time to blood culture positivity as a predictor of clinical outcomes and severity in adults with bacteremic pneumococcal pneumonia.

PLoS One 2017 7;12(8):e0182436. Epub 2017 Aug 7.

Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Ciber de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.

Objectives: We aimed to investigate the association between the time to positivity of blood culture (TTP) with clinical outcome and severity of pneumococcal bacteremic pneumonia.

Methods: Prospective observational study carried out in 278 hospitalized adult CAP patients with positive blood culture for Streptococcus pneumonia (2003-2015).

Results: A total of 278 cases of bacteremic pneumococcal pneumonia were analyzed, median age 62 (46; 79) years. Fifty-one percent of the cases had PSI IV-V. Twenty-one (8%) died within 30-days after admission. The analysis of the TTP showed that the first quartile of the TTP (9.2h) was the best cut-off for differentiating 2 groups of patients at risk, early (TTP <9.2 h) and late (TTP ≥9.2 h) detection groups (AUC 0.66 [95% CI 0.53 to 0.79]). Early TTP was associated with a statistically significant risk of invasive mechanical ventilation (18% vs. 6%, p = 0.007), longer length of hospital stay (12 days vs. 8 days, p<0.001), higher in-hospital mortality (15% vs. 4%, p = 0.010), and 30-day mortality (15% vs. 5%, p = 0.018). After adjustment for potential confounders, regression analyses revealed early TTP as independently associated with high risk of invasive mechanical ventilation (OR 4.60, 95% CI 1.63 to 13.03), longer length of hospital stay (β 5.20, 95% CI 1.81 to 8.52), higher in-hospital mortality (OR 5.35, 95% CI 1.55 to 18.53), and a trend to higher 30-day mortality (OR 2.47, 95% CI 0.85 to 7.21) to be a contributing factor.

Conclusion: Our results demonstrate that TTP is an easy to obtain surrogate marker of the severity of pneumococcal pneumonia and a good predictor of its outcome.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182436PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546626PMC
October 2017

Quantitative computed tomography analysis of the airways in patients with cystic fibrosis using automated software: correlation with spirometry in the evaluation of severity.

Radiol Bras 2016 Nov-Dec;49(6):351-357

PhD, MD, Pulmonologist, Professor in the Pulmonology Sector of the Department of Clinical Medicine of the Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.

Objective: To perform a quantitative analysis of the airways using automated software, in computed tomography images of patients with cystic fibrosis, correlating the results with spirometric findings.

Materials And Methods: Thirty-four patients with cystic fibrosis were studied-20 males and 14 females; mean age 18 ± 9 years-divided into two groups according to the spirometry findings: group I ( = 21), without severe airflow obstruction (forced expiratory volume in first second [FEV1] > 50% predicted), and group II ( = 13), with severe obstruction (FEV1 ≤ 50% predicted). The following tracheobronchial tree parameters were obtained automatically: bronchial diameter, area, thickness, and wall attenuation.

Results: On average, 52 bronchi per patient were studied. The number of bronchi analyzed was higher in group II. The correlation with spirometry findings, especially between the relative wall thickness of third to eighth bronchial generation and predicted FEV1, was better in group I.

Conclusion: Quantitative analysis of the airways by computed tomography can be useful for assessing disease severity in cystic fibrosis patients. In patients with severe airflow obstruction, the number of bronchi studied by the method is higher, indicating more bronchiectasis. In patients without severe obstruction, the relative bronchial wall thickness showed a good correlation with the predicted FEV1.
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http://dx.doi.org/10.1590/0100-3984.2015.0145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5238409PMC
January 2017

Executive summary of the diagnosis and treatment of urinary tract infection: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC).

Enferm Infecc Microbiol Clin 2017 May 23;35(5):314-320. Epub 2016 Dec 23.

Servicio de Enfermedades Infecciosas, Hospital Universitario Vall d'Hebron, Barcelona, Spain. Electronic address:

Most urinary tract infections (UTI) are uncomplicated infections occurring in young women. An extensive evaluation is not required in the majority of cases, and they can be safely managed as outpatients with oral antibiotics. Escherichia coli is by far the most common uropathogen, accounting for >80% of all cases. Other major clinical problems associated with UTI include asymptomatic bacteriuria, and patients with complicated UTI. Complicated UTIs are a heterogeneous group associated with conditions that increase the risk of acquiring infection or treatment failure. Distinguishing between complicated and uncomplicated UTI is important, as it influences the initial evaluation, choice, and duration of antimicrobial therapy. Diagnosis is especially challenging in the elderly and in patients with in-dwelling catheters. The increasing prevalence of resistant uropathogens, including extended-spectrum β-lactamases and carbapenemase-producing Enterobacteriaceae, and other multidrug-resistant Gram-negative organisms further compromises treatment of both complicated and uncomplicated UTIs. The aim of these Clinical Guidelines is to provide a set of recommendations for improving the diagnosis and treatment of UTI.
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http://dx.doi.org/10.1016/j.eimc.2016.11.005DOI Listing
May 2017

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms.

Antimicrob Agents Chemother 2017 02 24;61(2). Epub 2017 Jan 24.

Department of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Ceftazidime-avibactam (CAZ-AVI) is a recently approved β-lactam-β-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.
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http://dx.doi.org/10.1128/AAC.01964-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278727PMC
February 2017

Rapid Diagnosis of Staphylococcal Catheter-Related Bacteraemia in Direct Blood Samples by Real-Time PCR.

PLoS One 2016 29;11(8):e0161684. Epub 2016 Aug 29.

Department of Clinical Microbiology, Biomedical Diagnostic Centre (CDB), Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Spain.

Catheter-related bacteremia (CRB) is an important cause of morbidity and mortality among hospitalized patients, being staphylococci the main etiologic agents. The objective of this study was to assess the use of a PCR-based assay for detection of staphylococci directly from blood obtained through the catheter to diagnose CRB caused by these microorganisms and to perform a cost-effectiveness analysis. A total of 92 patients with suspected CRB were included in the study. Samples were obtained through the catheter. Paired blood cultures were processed by standard culture methods and 4 ml blood samples were processed by GeneXpert-MRSA assay for the detection of methicillin-susceptible (MSSA) or methicillin-resistant (MRSA) Staphylococcus aureus, and methicillin-resistant coagulase-negative staphylococci (MR-CoNS). Sixteen CRB caused by staphylococci were diagnosed among 92 suspected patients. GeneXpert detected 14 out of 16 cases (87.5%), including 4 MSSA and 10 MR-CoNS in approximately 1 hour after specimen receipt. The sensitivity and specificity of GeneXpert were 87.5% (CI 95%: 60.4-97.8) and 92.1% (CI 95%: 83-96.7), respectively, compared with standard culture methods. The sensitivity of GeneXpert for S. aureus was 100%. Regarding a cost-effectiveness analysis, the incremental cost of using GeneXpert was of 31.1€ per patient while the incremental cost-effectiveness ratio of GeneXpert compared with blood culture alones was about 180€ per life year gained. In conclusion, GeneXpert can be used directly with blood samples obtained through infected catheters to detect S. aureus and MR-CoNS in approximately 1h after sampling. In addition, it is cost-effective especially in areas with high prevalence of staphylococcal CRB.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161684PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003366PMC
August 2017

Evaluation of a Mixing versus a Cycling Strategy of Antibiotic Use in Critically-Ill Medical Patients: Impact on Acquisition of Resistant Microorganisms and Clinical Outcomes.

PLoS One 2016 16;11(3):e0150274. Epub 2016 Mar 16.

Department of Infectious Diseases, Hospital Clínic, IDIBAPS, Barcelona University, Barcelona, Spain.

Objective: To compare the effect of two strategies of antibiotic use (mixing vs. cycling) on the acquisition of resistant microorganisms, infections and other clinical outcomes.

Methods: Prospective cohort study in an 8-bed intensive care unit during 35- months in which a mixing-cycling policy of antipseudomonal beta-lactams (meropenem, ceftazidime/piperacillin-tazobactam) and fluoroquinolones was operative. Nasopharyngeal and rectal swabs and respiratory secretions were obtained within 48h of admission and thrice weekly thereafter. Target microorganisms included methicillin-resistant S. aureus, vancomycin-resistant enterococci, third-generation cephalosporin-resistant Enterobacteriaceae and non-fermenters.

Results: A total of 409 (42%) patients were included in mixing and 560 (58%) in cycling. Exposure to ceftazidime/piperacillin-tazobactam and fluoroquinolones was significantly higher in mixing while exposure to meropenem was higher in cycling, although overall use of antipseudomonals was not significantly different (37.5/100 patient-days vs. 38.1/100 patient-days). There was a barely higher acquisition rate of microorganisms during mixing, but this difference lost its significance when the cases due to an exogenous Burkholderia cepacia outbreak were excluded (19.3% vs. 15.4%, OR 0.8, CI 0.5-1.1). Acquisition of Pseudomonas aeruginosa resistant to the intervention antibiotics or with multiple-drug resistance was similar. There were no significant differences between mixing and cycling in the proportion of patients acquiring any infection (16.6% vs. 14.5%, OR 0.9, CI 0.6-1.2), any infection due to target microorganisms (5.9% vs. 5.2%, OR 0.9, CI 0.5-1.5), length of stay (median 5 d for both groups) or mortality (13.9 vs. 14.3%, OR 1.03, CI 0.7-1.3).

Conclusions: A cycling strategy of antibiotic use with a 6-week cycle duration is similar to mixing in terms of acquisition of resistant microorganisms, infections, length of stay and mortality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150274PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794237PMC
July 2016

[Allelic variants of the CYP2D6: *4, *6 and *10 in a sample of resident from the Aragua state, Venezuela].

Rev Peru Med Exp Salud Publica 2015 Oct;32(4):746-51

Instituto de Investigaciones Biomédicas Dr. Francisco J. Triana Alonso (BIOMED), Facultad de Ciencias de la Salud, Universidad de Carabobo Sede Aragua, Maracay, Aragua, Venezuela.

The aim of this study was to determine the CYP2D6: * 4, * 6 and * 10 gene variants frequency and to predict the metabolizer phenotype in a sample of 145 unrelated apparently healthy individuals residing in the state of Aragua, Venezuela. Genotypes were determined by Polymerase chain reaction assays followed by restriction endonucleases digestion. The metabolizer phenotype prediction was made based on the activity score system. The frequencies of CYP2D6 * 4, * 6 and * 10 allelic variants were 14.5%, 0.3% and 1%. A significant percentage of individuals were categorized as heterozygote-extensive/intermediate (23.5%) and poor metabolizers (4.1%), this information has potential clinical impact, because the CYP2D6 protein is involved in the metabolism of drugs frequently prescribed as: carvedilol, captopril, chloroquine, codeine, fluoxetine, fluvastatin, haloperidol, idarubicin, indinavir, imatinib, loperamide, nifedipine, ondansetron and tamoxifen.
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October 2015