Publications by authors named "Juan Picazo"

98 Publications

Comparison of performance of MALDI-TOF MS and MLST for biotyping carbapenemase-producing Klebsiella pneumoniae sequence types ST11 and ST101 isolates.

Enferm Infecc Microbiol Clin 2020 Dec 15. Epub 2020 Dec 15.

Servicio de Microbiología Clínica, Hospital Clínico San Carlos, IdISCC and IML Institutes, Germany; Departamento de Medicina, Facultad de Medicina, Universidad Complutense, Madrid, Spain. Electronic address:

Introduction: The rapid identification and detection of carbapenemase-producing Klebsiella pneumoniae (CPKP) isolates is crucial to ascertain outbreaks, as well as to limit their spread. The current reference method for this purpose is multilocus sequence typing (MLST), which is laborious and expensive. Consequently, alternative typing methods are gaining attention, such as Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS).

Methods: This study sought to analyze MALDI-TOF MS as a typing method using 44 CPKP isolates that were well characterized by MLST. The most common types of samples from which these pathogens were isolated were skin and soft tissues (32%) and urine (29%). Half of the CPKP isolates were from hospitalized patients. Two approaches were followed for the analysis of the mass peak data obtained by MALDI-TOF MS. The first using all peaks obtained and the second using a selection of 21 characteristic peaks.

Results: The selection of 21 characteristic peaks showed greater discrimination power for ST11 and ST101. Principal component analysis (PCA) indicated that this dataset could be efficiently grouped with lineal classifiers. A Support Vector Machine (SVM) was chosen for this purpose after checking its capacity to classify bacterial strains on the basis of MALDI-TOF MS information.

Conclusion: SVM was able to discriminate between ST11 and ST101 with high accuracy. In conclusion, our results reveal MALDI-TOF MS as a promising alternative technique for typing of CPKP isolates.
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http://dx.doi.org/10.1016/j.eimc.2020.10.018DOI Listing
December 2020

Impact of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children under 15 years old in Madrid, Spain, 2007 to 2016: The HERACLES clinical surveillance study.

Vaccine 2019 04 19;37(16):2200-2207. Epub 2019 Mar 19.

MedicalDepartment, Pfizer SLU, Madrid, Spain.

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Using the data from the HERACLES clinical surveillance study (2007-2016), we describe the population impact of the 13-valent pneumococcal conjugate vaccine (PVC13) on invasive pneumococcal disease (IPD) in children <15 years of age in the Community of Madrid, Spain. After six years of the inclusion of PCV13 in the vaccination calendar (2010-2016), and despite changes in the Regional Immunization Programme that limited its availability, the net benefit incidence rate (IR) of IPD fell by 70.1% (IRR 0.3 [95% CI: 0.22-0.4]; p ≤ 0.001), mainly due to a significant reduction (91%) in the PCV13 serotypes (IRR 0.09 [95% CI: 0.05-0.16], p ≤ 0.001). Furthermore, no significant changes were detected in the IR of IPD caused by non-PCV13 serotypes. The IRs of the aggressive, resistant and most prevalent serotype in the analysed population, the 19A serotype, dramatically decreased from the beginning to the end of the study (98%) [IRR 0.03 (95% CI: 0.00-0.19), p ≤ 0.001], to its almost total disappearance. Remarkably, this reduction led to a pronounced decline in the percentage of cefotaxime-resistant isolates and the incidence of meningitis cases. Assessment of the clinical impact revealed a reduction in the number of all clinical presentations of IPD, confirming the effectiveness of the PCV13. Finally, PCV13 detected by PCR is predicted to have a stronger impact than the one based on culture methods, which can overlook more than 20% of cases of IPD, mainly pleural empyemas.
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http://dx.doi.org/10.1016/j.vaccine.2019.03.015DOI Listing
April 2019

Effects of 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease in Infants Aged 0 to 90 Days in Madrid, Spain.

J Pediatric Infect Dis Soc 2018 May;7(2):175-176

Facultad de Medicina, Universidad Complutense de Madrid, Spain.

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http://dx.doi.org/10.1093/jpids/pix075DOI Listing
May 2018

Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children.

Vaccine 2017 08 12;35(35 Pt B):4646-4651. Epub 2017 Jul 12.

Medical Department, Pfizer Spain, Alcobendas, Madrid, Spain.

Objectives: To evaluate the impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children.

Methods: Children younger than 15years of age attending 27 hospitals in the Region of Madrid with confirmed pneumococcal meningitis were identified in a prospective surveillance study, from 2007 to 2015. Clinical data, neurological sequelae, pneumococcal vaccination status, serotyping and antibiotic susceptibility were recorded.

Results: One hundred and four cases of pneumococcal meningitis were identified, 63 during the period of routine 7-valent pneumococcal conjugate vaccine immunisation (May 2007-April 2010) and 41 during the period of 13-valent pneumococcal conjugate vaccine immunisation (May 2010-April 2015). When both periods were compared, a 62% (95% CI: 45-75%) decrease in the incidence of pneumococcal meningitis was observed, from 2.19 cases per 100,000 inhabitants in the PCV7 period to 0.81 per 100,000 inhabitants in the PCV13 period (p=0.0001), mainly due to an 83% (95% CI: 30-96%) reduction in cases caused by serotype 19A. Isolates not susceptible to cefotaxime (MIC>0.5μg/L) decreased from 27% to 8%, (p=0.02). Mean patient ages rose from 28.7months to 38.5months (p<0.05). Case fatality rate across both periods was 5%. An unfavourable outcome (death or neurological sequelae) occurred in 27% of patients, while the rate was similar in both periods. There was no increase in meningitis caused by pneumococcal serotypes not included in 13-valent pneumococcal conjugate vaccine throughout the years of the study.

Conclusions: Immunisation with 13-valent pneumococcal conjugate vaccine has reduced the rate of pneumococcal meningitis in children less than 15years, with a near-elimination of cefotaxime-resistant isolates, but morbidity has remained unchanged. A shift of pneumococcal meningitis towards slightly higher age groups was also observed.
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http://dx.doi.org/10.1016/j.vaccine.2017.06.070DOI Listing
August 2017

In-vitro activity of several antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA) isolates expressing aminoglycoside-modifying enzymes: potency of plazomicin alone and in combination with other agents.

Int J Antimicrob Agents 2017 Aug 31;50(2):191-196. Epub 2017 May 31.

Hospital Clínico San Carlos, Madrid, Spain.

This study investigated the in-vitro activity of clinically relevant aminoglycosides and new antimicrobial agents-plazomicin, ceftobiprole and dalbavancin-against 55 methicillin-resistant Staphylococcus aureus (MRSA) isolates producing aminoglycoside-modifying enzymes (AMEs). The checkerboard method was used to assess synergism between plazomicin and four antibiotics (fosfomycin, ceftobiprole, cefoxitin and meropenem), and time-kill assays were performed for the most active combinations. Among the aminoglycosides tested, plazomicin was the most active agent against MRSA, with >90% of isolates being inhibited at a minimum inhibitory concentration (MIC) of ≤1 mg/L. MIC and MIC values for ceftobiprole and dalbavancin were 2 and 4 mg/L, and 0.125 and 0.125 mg/L, respectively. The most prevalent AME gene was aac(6')Ie-aph(2″)Ia (87.3%), followed by ant(4')Ia (52.7%) and aph(3')IIIa (52.7%). Plazomicin activity was not affected by the type or number of enzymes detected. In checkerboard and time-kill assays, indifference was the most common result achieved for the antibiotic combinations. Notably, no antagonism was observed with any combination tested. Overall, plazomicin in combination with meropenem had the highest synergistic effect, demonstrating synergy against seven isolates in the checkerboard assay and three isolates in time-kill curves. In conclusion, plazomicin showed potent activity against aminoglycoside-resistant MRSA isolates, regardless of the number and type of AMEs present. These findings indicate the potential utility of plazomicin in combination with meropenem for the treatment of MRSA infections.
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http://dx.doi.org/10.1016/j.ijantimicag.2017.01.039DOI Listing
August 2017

Characterization and circulation of seasonal influenza viruses in Madrid, 2010-2016.

J Med Virol 2017 10 6;89(10):1726-1733. Epub 2017 Jun 6.

Department of Microbiology, Hospital Clínico San Carlos, Madrid, Spain.

Influenza virus infection is a major health care burden and is associated with significant morbidity and mortality. The 2009 influenza pandemic highlighted the importance of influenza surveillance. The objective of this study was to assess the epidemiology and activity of influenza A and B viruses in adults and children in the post-pandemic period with a special focus on the pediatric population. We performed a retrospective descriptive study involving adults and children with influenza-like illness at the Clinico San Carlos Hospital (Madrid, Spain) over six influenza seasons, between August 2010 and April 2016. Respiratory specimens were collected from 3131 patients and routinely processed for influenza diagnosis. Epidemiological analysis was performed in terms of gender, age, and seasonal distribution. Globally, Influenza A and B viruses were detected in the respiratory specimens of 696 (22.2%) of the 3131 studied population. Among all influenza positive specimens, 142 (20.4%) were influenza A(H1N1)pdm09, 61 (8.8%) were influenza A(H3N2), 321 (46.1%) were untypeable influenza A viruses and 166 (23.9%) were influenza B. Co-infection by both influenza A and B viruses was detected in six patients (0.9%). Meanwhile, co-infection with other non-influenza respiratory viruses was identified in 5 children and 20 adults. Influenza A(H1N1)pdm09 virus activity has been significantly high since the 2009 pandemic and has gradually replaced the previously circulating seasonal influenza A(H1N1) virus. Moreover, influenza A(H3N2) virus activity remained at low levels during the last winter season while influenza B virus isolates increased significantly over the past 2 years.
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http://dx.doi.org/10.1002/jmv.24857DOI Listing
October 2017

Effect of the different 13-valent pneumococcal conjugate vaccination uptakes on the invasive pneumococcal disease in children: Analysis of a hospital-based and population-based surveillance study in Madrid, Spain, 2007-2015.

PLoS One 2017 16;12(2):e0172222. Epub 2017 Feb 16.

Medical Department, Pfizer SLU, Madrid, Spain.

In the Community of Madrid, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent (PCV7) in the fully government-funded Regional Immunization Program (RIP) in May, 2010, but was later excluded in May, 2012, and included again in January, 2015. These unique changes allowed us to assess the impact of the different pneumococcal vaccination policies on PCV13 uptake in infants and on the incidence rate (IR) of invasive pneumococcal disease (IPD) in children <15 years old. In this prospective, active, surveillance study, we estimated PCV13 uptakes, IR and incidence rate ratios (IRR) for total IPD and for IPD caused by PCV13- and non-PCV13 serotypes in children <15 years, stratified by age, in four periods with different vaccination policies: fully government-funded PCV7 vaccination, fully government-funded PCV13, mixed public/private funding and only private funding. Vaccine uptakes reached 95% in periods with public-funded pneumococcal vaccination, but fell to 67% in the private funding period. Overall, IR of IPD decreased by 68% (p<0.001) in 2014-15, due to 93% reduction in the IR of PCV13-type IPD (p<0.001) without significant changes in non-PCV13-type IPD. A fully government-funded PCV13 vaccination program lead to high vaccine uptake and dramatic reductions in both overall and PCV13-type IPD IR. When this program was switched to private PCV13 vaccination, there was a fall in vaccine coverage and stagnation in the decline of PCV13-type IPD with data suggesting a weakening of herd immunity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172222PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312951PMC
August 2017

Plazomicin Activity against 346 Extended-Spectrum-β-Lactamase/AmpC-Producing Escherichia coli Urinary Isolates in Relation to Aminoglycoside-Modifying Enzymes.

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

Departamento de Medicina (Microbiología), Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.

The activity of plazomicin and clinically relevant aminoglycosides was tested against 346 extended-spectrum-β-lactamase/AmpC-producing Escherichia coli urinary isolates, and the results were correlated with the presence of aminoglycoside-modifying enzymes (AMEs). Data showed that plazomicin was very active against all ESBL/AmpC-producing E. coli urinary isolates. Its activity was not related to the AME genes studied.
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http://dx.doi.org/10.1128/AAC.02454-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278712PMC
February 2017

Detection of Escherichia coli ST131 clonal complex (ST705) and Klebsiella pneumoniae ST15 among faecal carriage of extended-spectrum β-lactamase- and carbapenemase-producing Enterobacteriaceae.

J Med Microbiol 2017 Feb 7;66(2):169-174. Epub 2017 Mar 7.

Microbiology Department, Hospital Clínico San Carlos, c/Martín Lagos s/n, Madrid 28040, Spain.

Purpose: The objective of the present study was to evaluate the prevalence of intestinal colonization with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) in non-selected hospitalized and non-hospitalized patients from the same geographic area of Madrid.

Methodology: A total of 501 fecal samples were screened. Diluted samples in saline were cultured in MacConkey agar plates with ceftazidime, cefotaxime, imipenem and meropenem disks. Colonies growing within the inhibition zone of either disk were selected. Characterization of ESBLs and CPEs were performed by PCR and sequencing. The Wider system was used for the bacterial identification. In addition, clonal analysis was carried out for species predominant among the fecal carriage.

Key Findings: Among the 501 patients enrolled, 43 (8.6 %) carried ESBL-E and 8 (1.6 %) patients exhibited CPE. The main intestinal colonizer among ESBL-E was CTX-M-producing Escherichia coli isolates in both settings (community and hospital). ST131 clonal complex was the most common among faecal ESBL-producing E. coli. All gut carriers of CPE were hospitalized patients, Klebsiella pneumoniae being the most prevalent species. Two OXA-48-producing K. pneumoniae isolates belonging to ST15 were detected.

Conclusion: Present study reveals that faecal carriage of ESBL is common among inpatients and outpatients, whereas carbapenemase producers are only present in the hospital setting. Therefore, active surveillance will be useful for reducing transmission of antimicrobial-resistant bacteria and preventing infection.
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http://dx.doi.org/10.1099/jmm.0.000399DOI Listing
February 2017

Evaluation of the Alere i Influenza A&B assay for rapid identification of influenza A and influenza B viruses.

J Med Microbiol 2016 Jun 11;65(6):456-461. Epub 2016 Mar 11.

Department of Microbiology, Hospital Clínico San Carlos, 28040 Madrid, Spain.

The Alere i Influenza A&B assay is a novel isothermal nucleic acid amplification assay capable of detecting and differentiating influenza A and B viruses in approximately 15 min with minimal hands-on time. This study was conducted in order to assess the performance of the Alere i Influenza A&B assay compared to molecular techniques, considered to be gold standard methods, to evaluate the results. A total of 119 nasopharyngeal swabs collected from inpatients with influenza-like illness were included in the study using both archived and prospectively collected samples from adults and children. Prospectively collected samples were also compared to the Alere BinaxNOW® Influenza A & B Card. The overall sensitivity for detection of influenza A and B viruses compared to those of molecular techniques were 65.96 % and 53.33 % respectively, while the specificity was 98.51 % and 95.96 %. Compared to the Alere BinaxNOW® Influenza A & B Card, the Alere i assay is considerably more sensitive for detection of influenza A and B viruses, although both tests demonstrated excellent specificity for diagnosis of influenza viruses.
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http://dx.doi.org/10.1099/jmm.0.000249DOI Listing
June 2016

In vitro activity of the next-generation aminoglycoside plazomicin alone and in combination with colistin, meropenem, fosfomycin or tigecycline against carbapenemase-producing Enterobacteriaceae strains.

Int J Antimicrob Agents 2015 Dec 9;46(6):616-21. Epub 2015 Sep 9.

Servicio de Microbiología Clínica, Hospital Clínico San Carlos, Plaza de Cristo Rey s/n, 28040 Madrid, Spain.

Carbapenemase-producing Enterobacteriaceae (CPE) cause serious infections and are associated with high mortality in part due to limited treatment options. The in vitro activities of the new aminoglycoside plazomicin and comparators were evaluated against a collection of 164 CPE (VIM-1, n=125; KPC-2, n=34; OXA-48, n=4; and IMP-22, n=1). MIC90 values of gentamicin, tobramycin and amikacin were 256, 64 and 16 mg/L, respectively. Plazomicin exhibited an MIC range of 0.12-4 mg/L with MIC50 and MIC90 values of 0.25 and 1 mg/L. The MICs of plazomicin did not correlate with the other aminoglycoside MICs, with the resistance phenotype or with the carbapenemase harboured. Chequerboard experiments against 10 carbapenemase-producing Klebsiella pneumoniae isolates showed that combinations of plazomicin with colistin yielded synergy against 60% of the strains. Synergy of plazomicin with meropenem or fosfomycin was detected against 20% and 25% of the isolates, respectively. Using time-kill methodology, the interactions of plazomicin at 2×, 1× and 0.5× MIC with meropenem, colistin, fosfomycin or tigecycline at steady-state concentrations against two K. pneumoniae carrying the VIM-1 enzyme were investigated. Bactericidal activity was evident for both isolates at 2× MIC of plazomicin. Synergy was observed when plazomicin was combined with meropenem, colistin or fosfomycin against both isolates, whilst the combination with tigecycline resulted in indifference. Antagonism was not observed for any of the combinations tested. The results of this study suggest that plazomicin may address the need for new therapeutic options for the treatment of infections due to CPE.
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http://dx.doi.org/10.1016/j.ijantimicag.2015.07.021DOI Listing
December 2015

[Update in Infectious Diseases 2015].

Rev Esp Quimioter 2015 Sep;28 Suppl 1:1-4

Francisco Javier Candel González. Servicio de Microbiología Clínica. Hospital Clínico San Carlos. UCM. Avda Dr. Lagos s/n. 28040. Madrid.

Infectious disease remains current worldwide. During the second half of 2014 an outbreak of ebolavirus hit West Africa with implications in the rest of the world. In fact, Spain declared the first imported case of this infection. Multiresistant enterobacteria outbreaks are emerging all around the world in a moment on which WHO draws attention to the limited resources, coining the term "post antibiotic era". On the other hand, 2014 went down in history as one in which hepatitis C is cured. Are also current HIV epidemiological control or strategies for antiviral and antifungal prophylaxis in immunocompromised hosts.
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September 2015

[Development of new vaccines].

Enferm Infecc Microbiol Clin 2015 Oct 2;33(8):557-68. Epub 2015 Sep 2.

Servicio de Microbiología Clínica, Hospital Clínico San Carlos, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España.

Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases.
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http://dx.doi.org/10.1016/j.eimc.2015.06.013DOI Listing
October 2015

Could ceftaroline be an alternative therapy for linezolid resistant Staphylococcus epidermidis infections in Intensive Care Medicine?

Rev Esp Quimioter 2015 Aug;28(4):214-6

Francisco Javier Candel González, Department of Clinical Microbiology and Infectious Diseases Hospital Clínico San Carlos, Madrid, Spain.

Introduction: Coagulase negative Staphylococcus continues generating interest in critically ill patients, due to their infections in extended admissions, in instrumented patients and due to their described multidrug resistance, which include glycopeptide heterorresistance and the increase in oxazolidinone resistance. Ceftaroline is a new cephalosporin with activity against resistant gram-positives, which, being betalactam, may provide adequate safety profile in the critical ill patient. The aim of this study was to determine the activity of ceftaroline and other antimicrobial agents against methicillin and linezolid-resistant Staphylococcus epidermidis.

Material And Methods: We studied susceptibility of ceftaroline, tigecycline, daptomycin and vancomycin in a total of sixty-eight methicillin and linezolid-resistant S. epidermidis isolates with clinical significance from an Intensive Care Unit, using E-test.

Results: All strains were susceptible to the four antimicrobial agents, regardless of the level of resistance to linezolid.

Conclusion: Ceftaroline could be an alternative in the treatment of methicillin and linezolid-resistant S. epidermidis infections in critically ill patients.
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August 2015

Can Plazomicin Alone or in Combination Be a Therapeutic Option against Carbapenem-Resistant Acinetobacter baumannii?

Antimicrob Agents Chemother 2015 Oct 13;59(10):5959-66. Epub 2015 Jul 13.

Microbiology Department, Hospital Clínico San Carlos, Madrid, Spain

Nosocomial pathogens can be associated with a variety of infections, particularly in intensive care units (ICUs) and in immunocompromised patients. Usually these pathogens are resistant to multiple drugs and pose therapeutic challenges. Among these organisms, Acinetobacter baumannii is one of the most frequent being encountered in the clinical setting. Carbapenems are very useful to treat infections caused by these drug-resistant Gram-negative bacilli, but carbapenem resistance is increasing globally. Combination therapy is frequently given empirically for hospital-acquired infections in critically ill patients and is usually composed of an adequate beta-lactam and an aminoglycoside. The purpose of this study was to evaluate the in vitro activity of plazomicin against carbapenem-resistant Acinetobacter baumannii. Amikacin was used as a comparator. The activity of plazomicin in combination with several different antibiotics was tested by disk diffusion, the checkerboard method, and time-kill studies. Synergy was consistently observed with carbapenems (meropenem and/or imipenem) along with plazomicin or amikacin. When the aminoglycosides were combined with other classes of antibiotics, synergy was observed in some cases, depending on the strain and the antibiotic combination; importantly, there was no antagonism observed in any case. These findings indicate the potential utility of plazomicin in combination with other antibiotics (mainly carbapenems) for the treatment of A. baumannii infections, including those caused by carbapenem-resistant isolates.
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http://dx.doi.org/10.1128/AAC.00873-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576036PMC
October 2015

Characterization of Inhibitor-Resistant TEM β-Lactamases and Mechanisms of Fluoroquinolone Resistance in Escherichia coli Isolates.

Microb Drug Resist 2015 Oct 6;21(5):512-5. Epub 2015 May 6.

Microbiology Department, Hospital Clínico San Carlos , Madrid, Spain .

The aim of present work was to characterize the inhibitor-resistant TEM (IRT) β-lactamases produced by Escherichia coli in Hospital Clínico San Carlos (Madrid, Spain). Mechanisms of fluoroquinolone resistance among IRT-producing strains were also studied. Isolates with susceptibility to cephalosporins and amoxicillin-clavulanate (AMC) resistance were collected in our hospital (November 2011-July 2012) from both outpatients and hospitalized patients. Among 70 AMC-resistant E. coli strains, 28 (40%) produced IRT enzymes. Most of them were uropathogens (82.1%) and recovered from outpatients (75%). Seven different IRT enzymes were identified with TEM-30 (IRT-2) being the most prevalent, followed by TEM-40 (IRT-11). A high rate of ciprofloxacin resistance was found among IRT-producing strains (50%). Most of the ciprofloxacin-resistant isolates showed ciprofloxacin minimum inhibitory concentration >32 mg/L and contained two mutations in both gyrA and parC genes. Four IRT enzyme producers harbored the qnr gene. ST131 clone was mainly responsible for both IRT enzyme production and ciprofloxacin resistance. In conclusion, data from this study show that the frequency of IRT producers was 40% and a high rate of ciprofloxacin resistance was found among IRT-producing isolates. Current and future actions should be taken into account to avoid or reduce the development of AMC and fluoroquinolone resistance in E. coli.
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http://dx.doi.org/10.1089/mdr.2015.0039DOI Listing
October 2015

The intangible benefits of vaccination - what is the true economic value of vaccination?

J Mark Access Health Policy 2015 12;3. Epub 2015 Aug 12.

Sanofi Pasteur MSD, Lyon, France.

Previous economic evaluations of new vaccines largely focussed on a narrow set of benefit categories, including primarily health gains and disease-related medical cost-savings, which probably resulted in underestimates of the true value of these vaccines. Other economic benefits of vaccines could be considered to assess the full economic value of vaccination, such as, for example, impact of the human papillomavirus vaccine on women's fertility through the decrease in precancerous lesions and, therefore, in the number of diagnostic and treatment interventions, which can be associated with an increased risk of subsequent pregnancy complications. Vaccines' impact on resource allocation at hospital level or on antimicrobial resistance, such as pneumococcal conjugate vaccines that have substantially reduced infections due to antimicrobial non-susceptible strains, thereby rendering the residual disease easier to treat, are other examples of intangible benefits of vaccination. These benefits are generally not considered in economic evaluations because they may not be immediately visible and are difficult to quantify. However, they should be taken into consideration in health technology assessments to enable those responsible for healthcare policies to make well-informed decisions on vaccination.
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http://dx.doi.org/10.3402/jmahp.v3.26964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802696PMC
April 2016

Recommendations for vaccination against pneumococcus in kidney patients in Spain.

Nefrologia 2014 8;34(5):545-51. Epub 2014 Jun 8.

Unlabelled: Invasive pneumococcal disease (IPD) is a serious problem in some risk groups: patients with stage 4 and 5 chronic kidney disease, stage 3 CKD undergoing immunosuppressive treatment, nephrotic syndrome or diabetes. These individuals are more susceptible to infections and more prone to suffering more severe and worsening symptoms. Vaccination is one of the strategies for preventing IPD, although vaccination coverage in this group at present is lower than desired. Currently, there are two vaccinations for adults. The polysaccharide vaccine (PPSV23), used for decades in patients over the age of 2, includes most serotypes (23), but it does not generate immune memory, causing the immune tolerance phenomenon and it does not act on nasopharyngeal colonisation. The conjugate vaccine (VNC13) can be used from infancy until adulthood (advice in patients over 18 years old received approval from the European Medicines Agency in July 2013) and generates a more powerful immune response than PPSV23 against the majority of the 13 serotypes that it includes. The 16 scientific societies most directly associated with the groups at risk of IPD have discussed and drafted a series of vaccination recommendations based on scientific evidence related to pneumococcal vaccination in adults with underlying conditions and pathologies, which are the subject of the document “

Consensus: Pneumococcal vaccination in adults with underlying pathology”. This text sets out the vaccination recommendations for the chronic kidney disease population.
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http://dx.doi.org/10.3265/Nefrologia.pre2014.May.12534DOI Listing
September 2016

Carbapenemase-producing Enterobacteriaceae in a tertiary hospital in Madrid, Spain: high percentage of colistin resistance among VIM-1-producing Klebsiella pneumoniae ST11 isolates.

Int J Antimicrob Agents 2014 May 22;43(5):460-4. Epub 2014 Feb 22.

Servicio de Microbiología Clínica, Hospital Clínico San Carlos, C/ Profesor Martín Lagos s/n, 28040 Madrid, Spain. Electronic address:

Here we describe the carbapenemase genes, genetic relatedness and antimicrobial susceptibility data of 123 carbapenemase-producing Enterobacteriaceae (CPE) clinical isolates recovered from 2010 to 2012, comprising Klebsiella pneumoniae (n = 79), Klebsiella oxytoca (n = 13), Serratia marcescens (n = 14), Enterobacter cloacae (n = 12), Enterobacter asburiae (n = 4) and Enterobacter aerogenes (n = 1). VIM-1 was the most common carbapenemase (n = 101) followed by KPC-2 (n = 19), OXA-48 (n = 2) and IMP-22 (n = 1). Among the K. pneumoniae isolates, nine sequence types (STs) were identified but two clones were dominant: ST11 (54/79) containing mainly VIM-1-producing isolates; and ST101 (13/79) constituted by KPC-2-producing strains. Pulsed-field gel electrophoresis (PFGE) showed a higher genetic diversity among the remaining Enterobacteriaceae. Amikacin and fosfomycin were the most active agents with 82.9% and 80.5% susceptibility, respectively. Non-susceptibility to tigecycline was detected in 36.5% of strains. Overall, colistin resistance was 24.7% and was as high as 47% in Enterobacter spp. An increase in colistin resistance from 13.5% to 31.7% was observed among K. pneumoniae isolates during the study period. Resistance was focused on ST11 since 83.3% of colistin-resistant strains belonged to this clone. The high level of colistin resistance observed in this study is worrying with respect to the already limited therapeutic options for infections caused by multidrug-resistant Gram-negative bacteria.
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http://dx.doi.org/10.1016/j.ijantimicag.2014.01.021DOI Listing
May 2014

Incidence of pediatric invasive pneumococcal disease in the Island of Majorca (2008-2010), an area with non-universal vaccination, and estimations of serotype & children population coverage by available conjugate vaccines.

BMC Infect Dis 2013 Oct 29;13:503. Epub 2013 Oct 29.

Microbiology Deparment, Hospital Clínico San Carlos, c/ Martín Lagos s/n, 28040 Madrid, Spain.

Background: The World Health Organization reported in 2007 that inclusion of PCV7 in national immunization programs should be seen as a priority, also encouraging countries to conduct appropriate surveillances for monitoring the impact of vaccination. These analyses should be conducted in specific geographical areas and should be aimed to evolution of invasive pneumococcal disease (IPD), by age groups, clinical presentation, and vaccine serotypes (and non-vaccine serotypes to detect possible replacement). This study aimed to monitor the evolution of IPD incidence in children <15 years requiring hospitalization in the Island of Majorca.

Methods: A prospective clinical surveillance of all culture and/or PCR-confirmed IPD in children <15 years was performed in all hospitals in the Island of Majorca (approximately 900,000 inhabitants) from January 2008 to December 2010. Incidence rate (IR) was calculated as cases/100,000 inhabitants using children population data.

Results: 66 IPDs were identified: 39 (59.1%) parapneumonic pneumococcal empyema (PPE), 16 (24.2%) bacteremic pneumonia (BP), 7 (10.6%) primary bacteremia, 3 (4.5%) meningitis, and 1 (1.5%) osteomyelitis. IRs in the three-year study period were: 64.22 for children 12- < 24 months, 37.21 for those 24-59 months, 22.62 for those <12 months, and 3.98 for children >59 months. By study year, IRs were 21.25 in 2008, 19.89 in 2009 and 9.80 in 2010. The reduction found in 2010 was significant and due to significant reductions in IRs of IPDs caused by serotypes included in PCV10 and PCV13. Overall, estimated serotype coverage by conjugate vaccines was 12.1% for PCV7, 37.9% for PCV10 and 65.2% for PCV13. Of the 66 hospitalized children with IPD, 20 had received at least one dose of PCV7 (13 cases with identified serotype). None of these 13 cases was caused by PCV7 serotypes, all were caused by PCV13 serotypes and only 53.8% by PCV10 serotypes.

Conclusions: The results of the present study evidence the importance of expanding the number of serotypes covered by PCV, and the added value of PCV13 with respect to PCV10 and PCV7, even in an area of low prevalence of 19A as the Island of Majorca.
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http://dx.doi.org/10.1186/1471-2334-13-503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826596PMC
October 2013

Expansion of serotype coverage in the universal pediatric vaccination calendar: short-term effects on age- and serotype-dependent incidence of invasive pneumococcal clinical presentations in Madrid, Spain.

Clin Vaccine Immunol 2013 Oct 7;20(10):1524-30. Epub 2013 Aug 7.

Microbiology Department, Hospital Clínico San Carlos, Madrid, Spain.

In Madrid, Spain, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the pediatric universal vaccination calendar in June 2010. A prospective clinical surveillance that included all children hospitalized with culture- and/or PCR-confirmed invasive pneumococcal disease (IPD) was performed in all Madrid hospitals. The incidence rates (IRs) (defined as the number of cases/100,000 inhabitants aged <15 years) in the PCV7 (May 2007 to April 2010) versus PCV13 (May 2011 to April 2012) periods were compared. There were 499 cases in the PCV7 period and 79 cases in the PCV13 period. Globally, the IR significantly decreased from 17.09 (PCV7 period) to 7.70 (PCV13 period), with significant decreases (PCV7 versus PCV13 periods) in all age groups for bacteremic pneumonia (5.51 versus 1.56), parapneumonic pneumococcal empyema (PPE) (5.72 versus 3.12), and meningitis (2.16 versus 0.97). In the PCV13 period, significant reductions (the IR in the PCV7 period versus the IR in the PCV13 period) were found in IPDs caused by PCV13 serotypes (13.49 versus 4.38), and specifically by serotypes 1 (globally [4.79 versus 2.53], for bacteremic pneumonia [2.23 versus 0.97], and for PPE [2.26 versus 1.17]), serotype 5 (globally [1.88 versus 0.00], for bacteremic pneumonia [0.89 versus 0.00], and for PPE [0.55 versus 0.00]), and serotype 19A (globally [3.77 versus 0.49], for bacteremic pneumonia [0.72 versus 0.00], for PPE [0.89 versus 0.00], and for meningitis [0.62 versus 0.00]). IPDs caused by non-PCV13 serotypes did not increase (IR, 3.60 in the PCV7 period versus 3.31 in the PCV13 period), regardless of age or presentation. No IPDs caused by the PCV13 serotypes were found in children who received 3 doses of PCV13. The number of hospitalization days and sanitary costs were significantly lower in the PCV13 period. The switch from PCV7 to PCV13 in the universal pediatric vaccination calendar provided sanitary and economical benefits without a replacement by non-PCV13 serotypes.
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http://dx.doi.org/10.1128/CVI.00239-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807202PMC
October 2013

Characterization and monitoring of linezolid-resistant clinical isolates of Staphylococcus epidermidis in an intensive care unit 4 years after an outbreak of infection by cfr-mediated linezolid-resistant Staphylococcus aureus.

Diagn Microbiol Infect Dis 2013 Jul 28;76(3):325-9. Epub 2013 May 28.

Department of Clinical Microbiology and Infectious Diseases, Hospital Clínico San Carlos, Universidad Complutense, 28040 Madrid, Spain.

Resistance to linezolid is emerging among Staphylococcus epidermidis isolates. During the 4 years following an outbreak of cfr-mediated linezolid-resistant S. aureus in our intensive care unit in 2008, we analyzed the clinical context and characterized the resistance mechanisms of 100 linezolid-resistant strains of S. epidermidis. The prevalence of the cfr gene in our strains reached 50% alone or in combination with other mechanisms. The mutation G2576T in domain V was found in 22% of strains, and both the cfr gene and G2576T in 44%. We also found an association between the cfr gene and mutations in the ribosomal protein L3. All 3 mechanisms co-occurred in 1 strain. MICs in combinations rose to >256 μg/mL. 58% of colonized patients, and 90% of infected patients had previously received linezolid for at last 10 days. Vancomycin was the main antibiotic in these infections, most of which were bacteremia. We found a high prevalence of the cfr gene in our clinical S. epidermidis isolates after the 2008 outbreak, despite having implemented isolation and control measures. The potential transmissibility of this agent, even without prior exposure to linezolid, can have serious epidemiological repercussions.
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http://dx.doi.org/10.1016/j.diagmicrobio.2013.04.002DOI Listing
July 2013

Detection and genotyping of human respiratory viruses in clinical specimens from children with acute respiratory tract infections.

Rev Esp Quimioter 2013 Mar;26(1):47-50

Microbiology Department, Hospital Clinico San Carlos, Madrid, Spain.

Respiratory virus infections are a major health concern and represent the primary cause of testing consultation and hospitalization for young children. The application of nucleic acid amplification technology, particularly multiplex PCR coupled with fluidic or fixed microarrays, provides an important new approach for the detection of multiple respiratory viruses in a single test. The aim of this study was to analyze respiratory samples from children with acute respiratory tract infection (ARTI) using a commercial array-based method (CLART(®) PneumoVir Genomica, Coslada, Spain). These tests were used to identify viruses in 281 nasopharyngeal samples obtained from children affected by ARTI. Samples were obtained form October 2008 to April 2009. Viruses were identified in 80% of the studied ARTI providing useful information on clinical features and epidemiology of specific agents affecting children in cold months. Multiple viral infections were found in 33.45% of the specimens.
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March 2013

[Increasing prevalence of fosfomycin resistance in extended-spectrum-beta-lactamase-producing Escherichia coli urinary isolates (2005-2009-2011)].

Rev Esp Quimioter 2013 Mar;26(1):43-6

Departamento de Microbiología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.

Introduction: Escherichia coli is the most important uropathogen. The appearance of extended- spectrum beta-lactamase (ESBL)-producing E.coli in urinary tract infections (UTI) constitutes an important therapeutic challenge that requires the study of its evolution throughout time in order to establish a suitable empirical treatment. Our aim was to determine the prevalence of ESBL-producing E. coli urinary isolates in 2005, 2009 and 2011. We also determined the antimicrobial coresistance to several agents, including fosfomycin.

Methods: We analyzed 5053, 6324 and 6644 E. coli isolates obtained from urine cultures in 2005, 2009 and 2011 respectively. Duplicate isolates were excluded. Antimicrobial susceptibility was determined by the Wider microdilution system (Soria Melguizo S.A.) and the phenotypic pattern of resistance that indicated a BLEE-producing E.coli was selected (CLSI 2009).

Results: 3.9% of strains (198) were ESBL producers in 2005, 7.3% (463) in 2009 and 8.7% (584) in 2011. Resistance to carbapenems was detected in 2009, they inhibited more than the 95% of strains in 2011. Among the non-beta-lactams, colistin was the most active antibiotic followed by nitrofurantoin. Ciprofloxacin and sulfamethoxazole-trimethoprim were not effective with 80% and 60% resistant isolates, respectively. An increasing resistance trend, from 0% to 9.3% in 2009 and 14.4% in 2011 was observed for fosfomycin.

Conclusions: From 2005 our institution had an increasing prevalence of ESBL-producing E. coli rising to 8.7% in 2011. Carbapenems are still the most active agents. The increase of resistance was significant for fosfomycin.
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March 2013

Rapid diagnosis of invasive pneumococcal disease in pediatric population.

J Microbiol Methods 2013 May 13;93(2):116-20. Epub 2013 Mar 13.

Microbiology Department, Hospital Clínico San Carlos, c/ Martín Lagos s/n, 28040 Madrid, Spain.

The aim of this study was to evaluate the Binax NOW immunochromatographic pneumococcal antigen test for the identification of Streptococcus pneumoniae in pleural and cerebrospinal fluids from children with suspected invasive pneumococcal disease. The results were compared with those obtained by PCR. Binax NOW was applied to these samples as recommended by the manufacturer for urine and cerebrospinal samples. Detection of pneumococcal DNA was performed by real-time PCR assay targeting the autolysin gene (lytA). Of the 199 samples analyzed, 131 were positive by both Binax NOW and lytA PCR, and 36 samples were negative by both techniques. Using the real-time PCR as a comparative method to the Binax for the detection of S. pneumoniae, the sensitivity and specificity of Binax NOW was 88% and 72.5%, respectively. Of the 145 positive samples analyzed by Binax NOW, 119 showed intense coloring of the sample line and 26 showed weak intensity. Conventional culture is the most common method in clinical settings, but Binax NOW is an easier and faster test for identifying S. pneumoniae in pleural and cerebrospinal fluids from children with suspected invasive pneumococcal disease.
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http://dx.doi.org/10.1016/j.mimet.2013.03.001DOI Listing
May 2013

Optimized method for Acinetobacter species carbapenemase detection and identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry.

J Clin Microbiol 2013 May 27;51(5):1589-92. Epub 2013 Feb 27.

Department of Clinical Microbiology, Hospital Clínico San Carlos, Madrid, Spain.

The use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for rapid detection and identification of the enzymes responsible for carbapenem resistance in Acinetobacter spp. appears as a promising option, but it will be necessary to have a standardized protocol that facilitates routine use. Based on the results reported herein and comparisons of several previously published reports, we identified the significant peaks for imipenem detection. Optimal bacterial inoculum and incubation time were established, and results obtained with and without dipicolinic acid (DPA) and Zn(2+) allowed us to distinguish between metallo-beta-lactamases and oxacillinases.
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http://dx.doi.org/10.1128/JCM.00181-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647957PMC
May 2013

Impact of introduction of conjugate vaccines in the vaccination schedule on the incidence of pediatric invasive pneumococcal disease requiring hospitalization in Madrid 2007 to 2011.

Pediatr Infect Dis J 2013 Jun;32(6):656-61

Microbiology Department, Hospital Clínico San Carlos, Madrid, Spain.

Background: Differences in invasive pneumococcal disease (IPD) in children are expected after a change from 7-valent pneumococcal conjugate vaccine (PCV7) to 13-valent pneumococcal conjugate vaccine (PCV13). Universal vaccination with PCV7 started in Madrid in November 2006, and it switched to PCV13 in June 2010.

Methods: A prospective, laboratory-confirmed (by culture or polymerase chain reaction), clinical surveillance including all pediatric IPD requiring hospitalization in Madrid was performed in all hospitals with a pediatric department and included four 1-year periods from May 2007 to April 2011. Incidence rate (IR) was calculated as number cases per 100,000 inhabitants using children population data.

Results: Six hundred fourteen IPDs were identified: 209 parapneumonic pneumococcal empyema, 191 bacteremic pneumonia, 75 primary bacteremia, 72 meningitis, 38 IPDs secondary to otic foci and 29 others. The incidence of IPD remained unchanged during 2007-2010 (IR=≈17.0), with a marked decrease in 2010-2011 (IR=11.34; P<0.05) attributable to reduction in children younger than 24 months (50.19 in 2008-2009 compared with 24.92 in 2010-2011; P<0.005). The incidence of bacteremic pneumonia (R²=0.966; β=1.132; P=0.017) and meningitis (R²=0.898; β=0.505; P=0.052) showed decreasing linear trends over time. The incidence of parapneumonic pneumococcal empyema increased in 2009-2010 but decreased in 2010-2011 (6.73 vs. 4.14; P=0.019). The incidence of IPDs by PCV13 serotypes was significantly (P≤0.004) lower in 2010-2011 (8.78) than in previous periods (IR=≈13.5).

Conclusions: Early data regarding changing from PCV7 to PCV13 use in the childhood vaccination calendar indicate that reductions in IR of bacteremic pneumonia and meningitis after PCV7 introduction (by reduction of cases by serotypes 1 and 19A) further decreased and there was a reversion of the increase in IR of parapneumonic pneumococcal empyema from 2010-2011, mainly because of reduction in serotype 1 and 19A cases.
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http://dx.doi.org/10.1097/INF.0b013e31827e8594DOI Listing
June 2013

[Significant increase in the colonisation of Staphylococcus aureus among medical students during their hospital practices].

Enferm Infecc Microbiol Clin 2013 Oct 24;31(8):516-9. Epub 2012 Nov 24.

Departamento de Microbiología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España; Servicio de Microbiología, Hospital Clínico San Carlos, Madrid, España. Electronic address:

Introduction: Staphylococcus aureus is a pathogen of major concern. The emergence of methicillin-resistant S. aureus (MRSA) has increasingly complicated the therapeutic approach of hospital-acquired infections. Surveillance of MRSA and control measures must be implemented in different healthcare settings, including screening programs for carriers. Our first aim was to determine the prevalence of methicillin-susceptible S. aureus (MSSA) and MRSA nasal carriage in medical students from the Clínico San Carlos Hospital (Madrid). As the MRSA carrier rate in healthcare workers is higher than in the general population, we hypothesised that carrier rate could be increased during their clinical practice in their last three years.

Methods: We performed an epidemiologic al study of the prevalence of S. aureus colonisation among a group of medical students, who were sampled in 2008 in their third-year, and in 2012 when this class was in its sixth year.

Results: We have found a significant increase in MSSA carriage, from 27% to 46%. There were no MRSA colonisations in the third-year, but one was found in the sixth-year group. The large majority of strains (89%) of strains were resistant to penicillin, and 27% to erythromycin and clindamycin. As 19 coagulase-negative Staphylococcus MR were also identified, a horizontal transfer of genes, such as mecA gene to S. aureus, could have occurred.

Conclusions: Medical students are both, at risk for acquiring, and a potential source of nosocomial pathogens, mainly MSSA. Therefore, they should take special care for hygienic precautions, such as frequent and proper hand washing, while working in the hospital.
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http://dx.doi.org/10.1016/j.eimc.2012.09.017DOI Listing
October 2013