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Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

IntroductionAnimal growth has been modelled using several mathematical functions (Logistic, Von Bertalanffy, Gompertz, etc.). These functions are described by a reduced number of parameters. In some cases, these parameters are assigned a biological interpretation (adult weight, maturing rate, etc.) and so the breeding goal can be closely related to the change of performance in these parameters, with the objective of altering the shape of the growth curve. In this sense, some studies have been focused on the estimation of (co)variance components of these parameters (Brown et al. 1976; Fitzbugh 1976; De Nise and Brinks 1985; Koenen and Groen 1996). These studies are based on a two-step procedure. In the first step, a growth curve is fitted separately to the data of each individual animal, afterwards, a mixed model analysis is applied to obtain (co)variance components. In this second step the estimates of production function parameters from the previous step are taken as records. Recently, Varona et al. (1997, 1998) have described a Bayesian procedure which allows the particular parameters of any production function to be estimated jointly and the (co)variance components between them. This procedure provides a considerable advantage over Maximun Likelihood approaches to joint analysis (Zucker et al. 1995) and makes use of all the available information. The aim of this study is to compare both procedures in a simulation scheme under the assumption of the Von Bertalanffy growth function. [ABSTRACT FROM AUTHOR]

In December 2022, an alert was published in the UK and other European countries reporting an unusual increase in the incidence of Streptococcus pyogenes infections. Our aim was to describe the clinical, microbiological, and molecular characteristics of group A Streptococcus invasive infections (iGAS) in children prospectively recruited in Spain (September 2022-March 2023), and compare invasive strains with strains causing mild infections. One hundred thirty isolates of S. pyogenes causing infection (102 iGAS and 28 mild infections) were included in the microbiological study: emm typing, antimicrobial susceptibility testing, and sequencing for core genome multilocus sequence typing (cgMLST), resistome, and virulome analysis. Clinical data were available from 93 cases and 21 controls. Pneumonia was the most frequent clinical syndrome (41/93; 44.1%), followed by deep tissue abscesses (23/93; 24.7%), and osteoarticular infections (11/93; 11.8%). Forty-six of 93 cases (49.5%) required admission to the pediatric intensive care unit. iGAS isolates mainly belonged to emm 1 and emm 12; emm 12 predominated in 2022 but was surpassed by emm 1 in 2023. Spread of M1 UK sublineage (28/64 M1 isolates) was communicated for the first time in Spain, but it did not replace the still predominant sublineage M1 global (36/64). Furthermore, a difference in emm types compared with the mild cases was observed with predominance of emm 1, but also important representativeness of emm 12 and emm 89 isolates. Pneumonia, the most frequent and severe iGAS diagnosed, was associated with the spe A gene, while the ssa superantigen was associated with milder cases. iGAS isolates were mainly susceptible to antimicrobials. cgMLST showed five major clusters: ST28-ST1357/ emm 1, ST36-ST425/ emm 12, ST242/ emm 12.37, ST39/ emm 4, and ST101-ST1295/ emm 89 isolates., Importance: Group A Streptococcus (GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an emm types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment., Competing Interests: The authors declare no conflict of interest.

Central metabolic pathways may play a major role in the virulence of pathogenic fungi. Here, we have investigated the susceptibility of a Candida parapsilosis mutant deficient in trehalase activity ( atc1 Δ/ ntc1 Δ strain) to the azolic compounds fluconazole and itraconazole. A time-course exposure to itraconazole but not fluconazole induced a significant degree of cell killing in mutant cells compared to the parental strain. Flow cytometry determinations indicated that itraconazole was able to induce a marked production of endogenous ROS together with a simultaneous increase in membrane potential, these effects being irrelevant after fluconazole addition. Furthermore, only itraconazole induced a significant synthesis of endogenous trehalose. The recorded impaired capacity of mutant cells to produce structured biofilms was further increased in the presence of both azoles, with itraconazole being more effective than fluconazole. Our results in the opportunistic pathogen yeast C. parapsilosis reinforce the study of trehalose metabolism as an attractive therapeutic target and allow extending the hypothesis that the generation of internal oxidative stress may be a component of the antifungal action exerted by the compounds currently available in medical practice., Competing Interests: The authors declare no conflicts of interest.

In fungi, the Mitogen-Activated Protein kinase (MAPK) pathways sense a wide variety of environmental stimuli, leading to cell adaptation and survival. The HOG pathway plays an essential role in the pathobiology of Candida albicans , including the colonization of the gastrointestinal tract in a mouse model, virulence, and response to stress. Here, we examined the role of Hog1 in the C. albicans response to the clinically relevant antifungal Micafungin (MF), whose minimum inhibitory concentration (MIC) was identical in the parental strain (RM100) and in the isogenic homozygous mutant hog1 (0.016 mg/L). The cell viability was impaired without significant differences between the parental strain, the isogenic hog1 mutant, and the Hog1 + reintegrant. This phenotype was quite similar in a collection of hog1 mutants constructed in a different C. albicans background. MF-treated cells failed to induce a relevant increase of both reactive oxygen species (ROS) formation and activation of the mitochondrial membrane potential in parental and hog1 cells. MF was also unable to trigger any significant activation of the genes coding for the antioxidant activities catalase ( CAT1 ) and superoxide dismutase ( SOD2 ), as well as on the corresponding enzymatic activities, whereas a clear induction was observed in the presence of Amphotericin B (AMB), introduced as a positive control of Hog1 signaling. Furthermore, Hog1 was not phosphorylated by the addition of MF, but, notably, this echinocandin caused Mkc1 phosphorylation. Our results strongly suggest that the toxic effect of MF on C. albicans cells is not mediated by the Hog1 MAPK and is independent of the generation of an internal oxidative stress in C. albicans .

Purpose . Fungal infections have increased in recent decades, with Candida albicans being the fourth most common aetiological agent of nosocomial infections. Disaccharide trehalose has been proposed as a target for the development of new antifungals. In C. albicans we have examined the susceptibility shown by two mutants deficient in trehalose biosynthesis, namely tps1Δ and tps2Δ , to amphotericin B (AmB) and micafungin (MF). Methodology . Minimum inhibitory concentrations (MICs) were calculated according to the Clinical and Laboratory Standards Institute (CLSI) criteria. Cell viability was assessed by cell counting. Intracellular reactive oxygen species (ROS) and the mitochondrial membrane potential were measured by flow cytometry, while the trehalose content and biofilm formation were determined by enzymatic assays. Results . While the tps1Δ mutant was highly sensitive to AmB exposure, its resistance to MF was similar to that of the wild-type. Notably, the opposite phenotype was recorded in the tps2Δ mutant. In turn, MF induced a significant level of endogenous ROS production in the parental SC5314 and tps2Δ cells, whereas the ROS formation in tps1Δ cells was virtually undetectable. The level of endogenous ROS correlated positively with the rise in mitochondrial activity. Only AmB was able to promote intracellular synthesis of trehalose in the parental strain; it was absent from tps1Δ cells and showed low levels in tps2Δ , confirming the unspecific dephosphorylation of trehalose-6P in C. albicans . Furthermore, the capacity of both tps1Δ and tps2Δ mutants to form biofilms was drastically reduced after AmB exposure, whereas it increased in tps1Δ cells treated with MF. Conclusion . Our data lend weight to the idea of using trehalose biosynthesis as a potential target for antifungal therapy.

Objective: Pseudomonas aeruginosa is one of the major pathogens causing hospital-acquired infections. In recent years, antimicrobial resistance is increasing and multidrug resistant (MDR) and extremely drug resistant (XDR) isolates have been associated with an increase of mortality. The aim of this study is to assess the clinical significance and analyze predictors and prognostic factors., Methods: Prospective case-control non-paired study involving 64 patients with P. aeruginosa nosocomial infection, 32 caused by susceptible P. aeruginosa and 32 by MDR/XDR including to carbapenems (XDR-C) strains, admitted at a third level hospital. The follow-up period was till hospital discharge or death and at 30 days after discharge. For all patients, clinical epidemiology and microbiological data were analyzed., Results: The incidence of MDR/XDR-C strains was 2.3 per 1000 admissions. Ten of which were VIM metallo-β-lactamase-producing. Independent predictor factors associated with MDR/XDR-C infections were: previous ICU or Resuscitation unit admission (OR 14.01; IC 95% 2.105-93.297) appearance >20 days after admission (OR 29.826; IC 95% 4.783-185.997) and leukocytosis (OR 10.0190; IC 95% 1.842-56.369). However, there were not statistically significant differences in clinical severity or mortality between both groups., Conclusions: The major risk factors associated with MDR/XDR-C infections were previous ICU or Resuscitation unit admission, appearance >20 days after admission and leukocytosis. MDR/XDR-C infections were not associated to increased mortality., (© The Author 2018. Published by Sociedad Española de Quimioterapia.)

Objectives: To analyze a cohort of patients with Enterococcus sp. bacteraemia., Patients and Methods: Retrospective and observational study of a cohort of non-pediatric in-patients with Enterococcus spp. bacteraemia (June 2007-September 2009). Data collection from clinical records was done according to a standard protocol. We analyzed epidemiological, clinical and microbiological data. Treatment with glycopeptides in non allergic patients or in case of betalactam susceptibility (ampicillin) was considered "optimizable"., Results: Three were 106 cases of bacteraemia (2.2/1000 admitted patients; 84% E. faecalis); 83% had an underlying condition; 88% nosocomial or health related cases. Urinary infection was present in 20% and primary bacteraemia in 47%. High level resistance to gentamicin (HLRG) was present in 60%; there was no vancomycin or linezolid resistance. Most frequent empiric treatments were penicillin-betalactamase inhibitor (25%) and glycopeptides (22%). Most frequent definitive treatment was glycopeptides (34%), being "optimized" 21% and 44% of empiric and definitive treatments, respectively. Mortality was 23% (related, 14%). In the multivariate analysis, risk factors associated with HLRG were nosocomial acquired infection (OR 6.083; 95CI% 1.428-25.915) and no-abdominal origin (OR 6.006; 95CI%1.398-25.805). In multivariate analysis, independent risk factors for mortality were: Pitt > 3 (OR 14.405; 95CI%2.236-92.808) and active empiric treatment (OR 8.849; 95CI% 1.101-71.429). Incidence in previous cohort was similar but HLRG rate has increased., Conclusions: Risk factors associated with HLRG were nosocomial acquired infection and no-abdominal origin. Risk factors for mortality were initial clinical severity and having received active empiric treatment. HLRG rate has increased.

Background and Objective: To analyse factors related to mortality and influence of antibiotic treatment on outcome in patients with nosocomial infection due to multidrug and carbapenem-resistant Acinetobacter baumannii (MDR-C AB)., Patients and Methods: Observational and prospective study of a cohort of adult patients with MDR-C AB infection. Data collection from clinical records was done according to a standard protocol (January 2007 through June 2008). Patients with MDR-C AB infection were identified by review of results of microbiology cultures from the hospital microbiology laboratory. Epidemiological and clinical variables and predictors of mortality were analysed., Results: 24 out of 101 cases were considered colonizations and 77 infections (27 bacteraemia); global mortality in infected patients was 49% (18 cases with bacteraemia and 20 with no bacteraemia). In the multivariate analysis, including the 77 cases of infection, the prognosis factors associated with mortality were age (OR 1.09; 95% CI 1.02-1.2), McCabe 1 (OR 33.98; 95% CI 4.33-266.85), bacteraemia (OR 9.89; 95% CI 1.13-86.13), inadequate empiric treatment (OR 16.7; 95% CI 2.15-129.79), and inadequate definitive treatment (OR 26.29; 95% CI 1.45-478.19). In the multivariate analysis including the 57 cases of infection with adequate definitive treatment, the prognosis factors associated with mortality were McCabe 1 (OR 24.08; 95% CI 3.67-157.96) and monotherapy versus combined treatment (OR 7.11; 95% CI 1.63-30.99)., Conclusions: Our cohort of patients with MDR-C AB infection is characterised by a very high mortality (49%); the severity of patients and inadequate treatment or monotherapy are statistically associated with mortality., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Antibiotic resistance is an old problem with new face as the rate of infections due to multidrug resistant bacteria is higher everyday and the number of new antibiotics to overwhelm the problem is becoming smaller. E. coli is the most frequent agent causing nosocomial or community-acquired bacteraemia being in our country 10% of them extended-spectrum beta-lactamases (ESBL) producing E. coli isolates. Nowadays the number of community- acquired or health-related infections caused by these ESBL producing E. coli is increasing. CTX-M has also become the most frequent ESBL compared to other enzymes. The role of these enzymes as a virulence factor increasing mortality in patients with bacteraemia due to E. coli is not well defined. The relevance of ESBL-E. coli seems to be related with the higher frequency of inadequate treatment and therefore the importance of identifying factors or features that might predict that the patient's infection is due to one of these isolates. In terms of prevention and control of infection measures, the role of patient's isolation is not clear but a proper prescription of antibiotics and antibiotic control policies are probably important to reduce the problem.

Background and Objective: To study an outbreak of nosocomial colonisation/infection due to multidrug and carbapenem resistant A. baumannii (ABMDR-C)., Patients and Methods: Prospective study of patients with ABMDR-C colonisation/infection (January 2007-June 2008). Epidemiological and clinical variables and predictors of infection versus colonization were analysed., Results: 24 out of 101 cases were considered colonisations and 77 infections (27 bacteraemia); global mortality (colonisations and infections) was 42% (4 colonisations and 38 infections -18 bacteraemia). All together, the incidence was 3.2/1000 admissions/day; 29% had been previously admitted and 79% had received previous antibiotic treatment (29% carbapenem; 34% piperacillin-tazobactam; 12.5% both); 78% had an underlying condition; 81% were UCI patients; 90% had gone through invasive procedures; 65% had another microorganism isolated. In multivariate analysis, infection predictor factors were isolation of ABMDR-C in respiratory samples (OR 5.406; 95% CI 1.419-20.599); male patients (OR 8.842; 95% CI 1.988-39.325); previous hospitalization (OR 9.720; 95% CI 1.383-68.291) and initial clinical severity (OR 30.897; 95% CI 5.533-172.543)., Conclusions: Our cohort of patients with ABMDR-C colonisation/infection is characterised by their underlying comorbidity, the high rate of previous invasive procedures, previous hospitalisation and previous broad-spectrum betalactam treatments (especially carbapenem). Initial severity and respiratory samples with ABMDR-C isolates were predictors of infection versus colonisation., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

The role of multidrug resistant Acinetobacter baumanii and its clinical relevance have been recently appreciated as a ubiquitous opportunistic nosocomial pathogen. Risk factors associated with A. baumanii infection include severe underlying diseases, previous surgery, invasive procedures, treatment with broad-spectrum antibiotics, length of hospital stay, admission to intensive care units (ICU). Carbapenem-multidrug resistant A. baumanii infections are probably associated to greater severity and more complications; in our cohort mortality was 49.3% and related mortality (within 72 hours) was 10.39%. However, severe underlying diseases probably play an important role in the clinical outcome of patients with MDR-C A. baumanii infection and controversy exists regarding the real mortality attributable to antimicrobial resistance because a high proportion of deaths took place > 7 days after diagnosis. Nevertheless, in our experience, carbapenem resistance, inappropriate therapy and monotherapy are associated to a higher mortality. Special attention should be paid to design well-controlled prospective clinical trials to determine the optimal antimicrobial therapy in critically ill patients suspected of having MDR Acinetobacter infection.

Airborne transmission is an important route for many microbial pathogens in outdoor and indoor environments, including hospitals. A 2-year-long survey of bioaerosol quality in operating theatres (OT), hospital rooms (HR) and maternity wards (MW) at a hospital in Murcia, Spain, was performed. Total aerobic counts (TAC) and fungal load (FL) were assessed using a microbiological air sampler (MAS-100 single-stage impactor). While fungal levels were below 1 cfu/m(3) (0-7.33 cfu/m(3)) in OT, they were higher in MW (mean, 6.9 cfu/m(3); range 0.44-44.67 cfu/m(3)) and in HR (mean, 10.6 cfu/m(3); range, 0-266 cfu/m(3)). In OT the aerobic counts were considerably higher, with a mean of 25.6 cfu/m(3) (range, 1.67-157 cfu/m(3)). MW and HR also showed higher means for total aerobic counts compared to OT. Seasonal changes were not detected in mould and bacteria levels in OT. Hospital renovation occurred during this study and OT adjacent to renovated areas were closed. A survey of TAC and FL in OT resumed when renovation was completed. We observed an outstanding increase in FL (more than 100 cfu/m(3)), particularly Aspergillus spp., during this period, but no significant changes in TAC were observed after renovation.

The choice of housekeeping proteins or genes for internal standards should be made carefully, taking into account the cell and tissue type, the experimental conditions, and the healthy/disease state(s) under consideration. Furthermore, as the correlation between transcriptional and translational levels of commonly used housekeeping genes is often discussed, this study shed light on the transcriptional levels of beta-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the translational levels of beta-actin, GAPDH, and beta-tubulin in an amyotrophic lateral sclerosis mouse model.

In the present study, we used the SOD1 (G93A) mutant transgenic mice as a model of amyotrophic lateral sclerosis (ALS). This model is widely used as a laboratory tool to study experimental treatments in vivo for ALS to investigate new therapeutic strategies for this neurodegenerative disease. Such studies require the objective quantification of different parameters while mice develop the disease. We have applied a battery of different and specific tests: scoring of motor deficits by a trained observer, weighing, survival measure, hanging wire test, rotarod task and electromyography, most of them commonly used to evaluate G93A animals. We have critically compared these methods, showing the significant influence of gender on the onset of symptoms, and the optimal moment to apply each test. These results should be taken into account in future therapeutic assays on this ALS model.

The aim of the present study was to characterize a new lipid detected in the opportunistic pathogen Corynebacterium amycolatum. It was identified as acyl-phosphatidylinositol (acyl-PI), and revealed as a mixture of homologues compounds by electrospray ionization mass spectrometry, with pseudomolecular ions, (M-H)-, observed at 1099 (the major one) 1113, and 1127. Acyl-PI exclusively contained octadecenoyl on the inositol moiety (as 3-O-acyl), an unsaturated fatty acyl (mostly octadecenoyl) at sn-1 position of the glycerol and a saturated fatty acyl (mainly hexadecanoyl) at the sn-2 position. Acyl-PI constitutes a new natural substance and seems to be unique among the phospholipids of C. amycolatum. Other more complex molecules, previously undetected, and assigned in this work to several acyl forms of phosphatidylinositol trimannosides, lacked octadecenoyl in their polar heads. The present study reveals the existence of acyl-PI in C. amycolatum as rather unexpected finding and, additionally, gives evidence for the ability of this species to synthesize a great variety of inositol-containing phospholipids.

The Bartels enzyme immunoassay (EIA), Biotest EIA, and Binax NOW immunochromatographic test (ICT) urinary antigen kits for the detection of Legionella pneumophila serogroup 1 were compared using 178 frozen urine samples. When nonconcentrated urine samples were used, the sensitivity levels of both enzyme EIAs were significantly higher than the sensitivity level of the ICT (Bartels EIA, 71.3%; Biotest EIA, 65.1%; Binax NOW ICT, 37% [P < 0.001]). After concentration of the urine samples, no significant differences in sensitivity were found among the three tests.

A comparative study on phospholipids of Corynebacterium amycolatum, Corynebacterium jeikeium and Corynebacterium urealyticum was carried out using fast-atom bombardment (FAB) and electrospray ionization (ESI) mass spectrometry. Data obtained indicate the presence of acylphosphatidylglycerol (APG), diphosphatidylglycerol, phosphatidylglycerol (PG), phosphatidylinositol (PI) and triacylphosphatidylinositol dimannosides (Ac(3)PIM(2)) in these bacteria. In general, octadecenoyl and hexadecanoyl fatty acyl moieties predominated in phospholipids of C. amycolatum, whereas high levels of hexadecenoyl were found in C. jeikeium and C. urealyticum. Mass spectra from purified APG and PG indicated that the sn-1 position of the glycerol was occupied by octadecenoyl in the three species studied. Notably, several major molecular species of PI and Ac(3)PIM(2) from C. urealyticum contained significant amounts of a moiety identified as 10-methyleneoctadecanoyl, located at the sn-1 position of these molecules. On the other hand, multiantibiotic resistant and susceptible strains of C. amycolatum differed in several minor phospholipid fatty acids of 19 carbon atoms, identified as 10-methyloctadecenoic, 10-methyloctadecanoic (tuberculostearic acid) and 10-methyleneoctadecanoic. The results demonstrate an overall similarity among the phospholipids of the different species studied but also significant differences related to the acyl chains of the glycerol moiety of these compounds, notably the high levels of an unusual fatty acyl moiety in inositol-containing phospholipids of C. urealyticum.

A chemotaxonomic study of some corynebacteria isolated from clinical samples revealed characteristic thin-layer chromatographic patterns for meso-diaminopimelic acid containing species included in the genera Corynebacterium, Dermabacter and Brevibacterium. Notably, a specific compound was consistently detected in mycolic acid containing species of the genus Corynebacterium. This compound was composed by glycerol and mycolic acids and structural analyses carried out by fast atom bombardment mass spectrometry in C. minutissimum confirmed its identification as mycoloylglycerol. The chain length of mycoloyl groups in this molecule ranged from 28 to 34 carbon atoms, being mono-, di- or triunsaturated. Detection of mycoloylglycerol by thin-layer chromatography may be thus useful for the rapid inclusion of a great variety of corynebacteria of clinical origin in the genus Corynebacterium in laboratories employing chromatographic techniques as an adjunct for the identification of these microorganisms.