In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) Against Contemporary Blood Isolates From Medically Relevant Species of Candida: A European Study.

Background: Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis. Objective: The aim of this study was to assess the in vitro activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of Candida. Methods: Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163 Candida albicans, 108 Candida parapsilosis, 60 Candida glabrata, 40 Candida tropicalis, 29 Candida krusei, 20 Candida orthopsilosis, 6 Candida guilliermondii, 2 Candida famata, 2 Candida lusitaniae, and 1 isolate each of Candida bracarensis, Candida catenulata, Candida dubliniensis, and Candida kefyr. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22 Candida auris from different clinical specimens were evaluated. Results: Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for C. albicans (geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for C. tropicalis (geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC50s (mg/L) against Candida spp. were 0.125/0.06 for C. albicans, 0.5/0.5 for C. parapsilosis, 0.25/0.25 for C. glabrata, 0.5/0.5 for C. tropicalis, 1/1 for C. krusei, 4/2 for C. orthopsilosis, and 0.5/0.5 for C. auris. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%) C. parapsilosis, 4 (5%) C. glabrata, and 1 (2.5%) C. tropicalis. Conclusion: Ibrexafungerp showed a potent in vitro activity against Candida.

Invasive Fusariosis in Nonneutropenic Patients, Spain, 2000-2015.

Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000-2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000-2009 to 0.22 cases per 100,000 admissions in 2010-2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.

Azole and Amphotericin B MIC Values against Aspergillus fumigatus: High Agreement between Spectrophotometric and Visual Readings Using the EUCAST EDef 9.3.2 Procedure.

The EUCAST EDef 9.3.2 procedure recommends visual readings of azole and amphotericin B MICs against Aspergillus spp. Visual determination of MICs may be challenging. In this work, we aim to obtain and compare visual and spectrophotometric MIC readings of azoles and amphotericin B against Aspergillus fumigatussensu lato isolates. A total of 847 A. fumigatussensu lato isolates (A. fumigatus sensu stricto [n = 828] and cryptic species [n = 19]) were tested against amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole using the EUCAST EDef 9.3.2 procedure. Isolates were classified as susceptible or resistant/non-wild type according to the 2020 updated breakpoints. The area of technical uncertainty for the azoles was defined in the updated breakpoints. Visual and spectrophotometric (fungal growth reduction of >95% compared to the control, read at 540 nm) MICs were compared. Essential (±1 2-fold dilution) and categorical agreements were calculated. Overall, high essential (97.1%) and categorical (99.6%) agreements were found. We obtained 100% categorical agreements for amphotericin B, itraconazole, and posaconazole, and consequently, no errors were found. Categorical agreements were 98.7 and 99.3% for voriconazole and isavuconazole, respectively. Most of the misclassifications for voriconazole and isavuconazole were found to be associated with MIC results falling either in the area of technical uncertainty or within one 2-fold dilution above the breakpoint. The resistance rate was slightly lower when the MICs were obtained by spectrophotometric readings. However, all relevant cyp51A mutants were correctly classified as resistant. Spectrophotometric determination of azole and amphotericin B MICs against A. fumigatussensu lato isolates may be a convenient alternative to visual endpoint readings.

Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity.

BACKGROUND: For still unclear reasons, chronic airway infection often occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), particularly in those with more severe airflow limitation. Fatty-acid binding protein 4 (FABP4) is an adipokine involved in the innate immune response against infection produced by alveolar macrophages (Mɸ). We hypothesized that airway levels of FABP4 may be altered in COPD patients with chronic airway infection. METHODS: In this prospective and controlled study we: (1) compared airway FABP4 levels (ELISA) in induced sputum, bronchoalveolar lavage fluid (BALF) and plasma samples in 52 clinically stable COPD patients (65.2 ± 7.9 years, FEV1 59 ± 16% predicted) and 29 healthy volunteers (55.0 ± 12.3 years, FEV1 97 ± 16% predicted); (2) explored their relationship with the presence of bacterial airway infection, defined by the presence of potentially pathogenic bacteria (PPB) at ≥103 colony-forming units/ml in BALF; (3) investigated their relationship with the quantity and proportion of Mɸ in BALF (flow cytometry); and, (4) studied their relationship with the severity of airflow limitation (FEV1), GOLD grade and level of symptoms (CAT questionnaire). RESULTS: We found that: (1) airway levels of FABP4 (but not plasma ones) were reduced in COPD patients vs. controls [219.2 (96.0-319.6) vs. 273.4 (203.1-426.7) (pg/ml)/protein, p = 0.03 in BALF]; (2) COPD patients with airway infection had lower sputum FABP4 levels [0.73 (0.35-15.3) vs. 15.6 (2.0-29.4) ng/ml, p = 0.02]; (3) in COPD patients, the number and proportion of Mɸ were positively related with FABP4 levels in BALF; (4) BALF and sputum FABP4 levels were positively related with FEV1, negatively with the CAT score, and lowest in GOLD grade D patients. CONCLUSIONS: Airway FABP4 levels are reduced in COPD patients, especially in those with airway infection and more severe disease. The relationship observed between Mɸ and airway FABP4 levels supports a role for FABP4 in the pathogenesis of airway infection and disease severity in COPD.

Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.

Verrucous Plaque With Unusually Large Candida Blastoconidia: A Unique Clinicopathological Presentation of Systemic Mucocutaneous Candidiasis.

Mucocutaneous candidiasis is a common infection affecting both immunocompetent and immunosuppressed individuals. Diversity in the clinical and histopathological presentation of mucocutaneous candidiasis is well known. However, the occurrence of cutaneous verrucous lesions and giant yeast-like structures has been rarely reported. In this article, we describe a case of disseminated mucocutaneous candidiasis in an immunosuppressed patient who presented as a verrucous plaque on the scrotum with giant Candida blastoconidia. This peculiar presentation expands the clinicopathological spectrum of mucocutaneous candidiasis and highlights the wide range of clinical manifestations and great morphologic variability of this common fungal infection.

Identification of Pseudomonas aeruginosa and airway bacterial colonization by an electronic nose in bronchiectasis.

RATIONALE: Airway colonization by Potentially Pathogenic Microorganisms (PPM) in bronchiectasis is associated with worse clinical outcomes. The electronic nose is a non-invasive technology capable of distinguishing volatile organic compounds (VOC) in exhaled breath. We aim to explore if an electronic nose can reliably discriminate airway bacterial colonization in patients with bronchiectasis. METHODS: Seventy-three clinically stable bronchiectasis patients were included. PPM presence was determined using sputum culture. Exhaled breath was collected in Tedlar bags and VOC breath-prints were detected by the electronic nose Cyranose 320®. Raw data was reduced to three factors with principal component analysis. Univariate ANOVA followed by post-hoc least significant difference test was performed with these factors. Patients were then classified using linear canonical discriminant analysis. Cross-validation accuracy values were defined by the percentage of correctly classified patients. RESULTS: Forty-one (56%) patients were colonized with PPM. Pseudomonas aeruginosa (n = 27, 66%) and Haemophilus influenzae (n = 7, 17%) were the most common PPM. VOC breath-prints from colonized and non-colonized patients were significantly different (accuracy of 72%, AUROC 0.75, p < 0.001). VOC breath-prints from Pseudomonas aeruginosa colonized patients were significantly different from those of patients colonized with other PPM (accuracy of 89%, AUROC 0.97, p < 0.001) and non-colonized patients (accuracy 73%, AUROC 0.83, p = 0.007). CONCLUSIONS: An electronic nose can accurately identify VOC breath-prints of clinically stable bronchiectasis patients with airway bacterial colonization, especially in those with Pseudomonas aeruginosa.

Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

[This corrects the article DOI: 10.3389/fmicb.2018.00516.].

Pseudomonas aeruginosa resistance patterns and clinical outcomes in hospitalized exacerbations of COPD.

BACKGROUND AND OBJECTIVE: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to Pseudomonas aeruginosa (PA) are associated with worse outcomes. PA antibiotic resistance is important to determine treatment and may influence clinical outcomes. The aim was to study clinical characteristics and outcomes in patients with AECOPD associated with PA based on their antibiotic resistance. METHODS: This was a prospective observational study including all patients with AECOPD and positive PA sputum culture admitted in a respiratory ward in a tertiary hospital in Barcelona during 2013-2014. PA was defined as resistant (PA-R) when the antibiogram showed ≥1 resistance. RESULTS: Four hundred one patients with AECOPD were evaluated. Of them, 54 (13%) had a positive PA sputum culture. Eighty-two per cent were men, median age was 77 (SD 7) years old and FEV1 was less than 36% (SD 17) of predicted value. PA-R was isolated in 35 patients (66%), and PA-sensitive (PA-S) was isolated in 18 (34%) patients. No differences were found in demographics, lung function and comorbidities among groups. PA-R patients were more likely exposed to prior oral corticosteroids (77% vs 44%, P = 0.03) and antibiotics (77% vs 31%, P = 0.01), respectively. AECOPD patients associated with PA-S were more likely to die at 30 days (odds ratio 13.53, 95% confidence interval: 1.14-69.56, P = 0.03) and 90 days (odds ratio 7.09, 95% confidence interval: 1.33-37.89, P = 0.02), respectively. CONCLUSION: Pseudomonas aeruginosa-resistant affects patients with severe AECOPD and previous use of corticosteroids and antibiotics. The presence of PA-S is associated with higher mortality. These results may suggest increased virulence in PA-S strains causing acute infections.

Airway Mucin 2 Is Decreased in Patients with Severe Chronic Obstructive Pulmonary Disease with Bacterial Colonization.

RATIONALE: Mucins are essential for airway defense against bacteria. We hypothesized that abnormal secreted airway mucin levels would be associated with bacterial colonization in patients with severe chronic obstructive pulmonary disease (COPD) Objectives: To investigate the relationship between mucin levels and the presence of potentially pathogenic micro-organisms in the airways of stable patients with severe COPD Methods: Clinically stable patients with severe COPD were examined prospectively. All patients underwent a computerized tomography scan, lung function tests, induced sputum collection, and bronchoscopy with bronchoalveolar lavage (BAL) and protected specimen brush. Patients with bronchiectasis were excluded. Secreted mucins (MUC2, MUC5AC, and MUC5B) and inflammatory markers were assessed in BAL and sputum by ELISA. MEASUREMENTS AND MAIN RESULTS: We enrolled 45 patients, with mean age (±SD) of 67 (±8) years and mean FEV1 of 41 (±10) % predicted. A total of 31% (n = 14) of patients had potentially pathogenic micro-organisms in quantitative bacterial cultures of samples obtained by protected specimen brush. Patients with COPD with positive cultures had lower levels of MUC2 both in BAL (P = 0.02) and in sputum (P = 0.01). No differences in MUC5B or MUC5AC levels were observed among the groups. Lower MUC2 levels were correlated with lower FEV1 (r = 0.32, P = 0.04) and higher sputum IL-6 (r = -0.40, P = 0.01). CONCLUSIONS: Airway MUC2 levels are decreased in patients with severe COPD colonized by potentially pathogenic micro-organisms. These findings may indicate one of the mechanisms underlying airway colonization in patients with severe COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01976117).

Efficacy of the FilmArray blood culture identification panel for direct molecular diagnosis of infectious diseases from samples other than blood.

Molecular-based techniques reduce the delay in diagnosing infectious diseases and therefore contribute to better patient outcomes. We assessed the FilmArray blood culture identification (BCID) panel (Biofire Diagnostics/bioMérieux) directly on clinical specimens other than blood: cerebrospinal, joint, pleural and ascitic fluids, bronchoscopy samples and abscesses. We compared the results from 88 samples obtained by culture-based techniques. The percentage of agreement between the two methods was 75 % with a Cohen κ value of 0.51. Global sensitivity and specificity using the FilmArray BCID panel were 71 and 97 %, respectively. Sensitivity was poorer in samples with a low bacterial load, such as ascitic and pleural fluids (25 %), whereas the sensitivity for abscess samples was high (89 %). These findings suggest that the FilmArray BCID panel could be useful to perform microbiological diagnosis directly from samples other than positive blood cultures, as it offers acceptable sensitivity and moderate agreement with conventional microbiological methods. Nevertheless, cost-benefit studies should be performed before introducing this method into algorithms for microbiological diagnostics.

Secreted mucins and airway bacterial colonization in non-CF bronchiectasis.

BACKGROUND AND OBJECTIVE: Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non-cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms (PPM) in the airways of stable bronchiectasis patients. METHODS: Clinically stable bronchiectasis patients were studied prospectively at two centres. Patients with other pulmonary conditions were excluded. Spontaneous sputum was subject to bacterial culture, and secreted mucins (MUC2, MUC5AC and MUC5B) were measured in sputum supernatants by ELISA. RESULTS: A total of 50 patients were included. PPM were identified from sputum samples in 30 (60%), with Pseudomonas aeruginosa (n = 10) and Haemophilus influenzae (n = 10) as the most common PPM. There were no baseline differences among airway colonized and non-colonized patients. Patients with airways colonized by PPM presented higher levels of airway MUC2. No differences in MUC5AC levels were found among groups, whereas MUC5B levels were undetectable. Patients with P. aeruginosa colonization expressed the highest levels of MUC2. High levels of MUC2 and MUC5AC are also correlated with disease severity using the Bronchiectasis Severity Index. CONCLUSIONS: Airway MUC2 levels were higher in bronchiectasis patients colonized with PPM compared with those without airway colonization, especially in patients with P. aeruginosa. These findings suggest that airway-secreted mucins levels may play a role in the pathogenesis of airway infection in non-CF bronchiectasis.

La infección neonatal tardía por Streptococcus agalactiae en el área de Barcelona (1996-2010) / Streptococcus agalactiae late-onset neonatal infections in Barcelona (1996-2010)

OBJETIVO: Analizar las características de la sepsis neonatal tardía (SNT) por estreptococo del grupo B (EGB) y la evolución de su incidencia en 8 hospitales del área de Barcelona a lo largo de los 15 años de consolidación de las medidas de prevención de la infección neonatal precoz. MÉTODOS: Revisión retrospectiva de los pacientes diagnosticados de SNT por EGB desde 1996 a 2010. RESULTADOS: Se diagnosticaron 143 pacientes, de los que 51 habían nacido en otros centros. La incidencia global fue del 0,4 2‰ de recién nacidos vivos (RNV), oscilando entre el 0,14‰ en 2000 y el 0,80‰ en 2009. Se observó una tendencia al incremento del riesgo discreta pero sostenida a lo largo de los años, del 6,9% en las SNT totales, aunque sin la suficiente significación estadística. El 63,6% de los pacientes presentaron sepsis/bacteriemia, el 32,8% meningitis y el 3,5% artritis/osteomielitis. De los casos en los que se pudo obtener información sobre los antecedentes obstétricos, el 53% de las madres presentaron cultivo positivo a EGB al final del embarazo, el 53,8% recibieron profilaxis antibiótica intraparto y el 41,2% presentaron algún factor de riesgo, principalmente parto prematuro en el 35,9% de los casos. La mortalidad fue del 2,8%, y los serotipos mayoritarios, el III y el Ia. CONCLUSIONES: La incidencia de SNT por EGB no ha disminuido a pesar de las medidas de prevención de la SNP, y la posibilidad de su aparición debe ser tenida en cuenta

OBJECTIVE: To study the characteristics and evolution of group B Streptococcus (GBS) late-onset diseases, over a period of 15 years in 8 hospitals the Barcelona area and analyze the possible impact of prophylactic measures for the prevention of early-onset neonatal infections. METHODS: Retrospective review of all patients diagnosed with late-onset neonatal disease due to GBS from 1996 to 2010. RESULTS: A total of 143 patients were diagnosed. Of these, 51 were born in others hospitals. The overalll incidence was 0.42 per 1000 live births, varying between 0.14‰ in the year 2000 and 0.80‰ in 2009. A slight but sustained tendency of increased risk was observed over the years, 6.9% in the overall disease (with no statistical significance). Sepsis/bacteremia was detected in 63.6% of the newborns, meningitis in 32.8%, and arthritis/osteomyelitis in 3.5%. In cases with known obstetrics dates, 53% of mothers had been colonized by GBS during pregnancy, 53.8% received intrapartum antibiotic prophylaxis, and 41.2% had some obstetric risk factors, particularly premature birth in 35.9%. There was a 2.8% mortality rate in the neonates, and predominant serotypes were III and Ia. CONCLUSIONS: The incidence of GBS late-onset disease has not decreased despite the control practices of early-onset disease, and possibility of this appearing must be taken into account

Fungemia in a Spanish hospital: the role of Candida parapsilosis over a 15-year period.

BACKGROUND: Candida parapsilosis is one of the main causes of fungemia in tertiary-care hospitals. Few studies have analysed the changes in its distribution over a long period. We compared the distribution of C. parapsilosis with that of other fungi over a 15-y period in a tertiary hospital. METHODS: The susceptibility of C. parapsilosis was analysed using the new species-specific clinical breakpoints. The C. parapsilosis complex species were differentiated molecularly. RESULTS: From January 1997 to December 2011, 360 isolates causing 350 episodes of fungemia were isolated. C. parapsilosis was the second most frequently isolated species (20%); only 1 C. orthopsilosis was identified and there were no C. metapsilosis. The remaining episodes were caused by C. albicans (43.1%), C. tropicalis (14.4%), C. glabrata (11.7%), and other fungal species (10.8%). The incidence of candidemia increased more than two-fold between 2009 and 2011 (from 3.3 to 7.4 cases/100,000 population), and C. parapsilosis and C. glabrata fungemia increased throughout the period. C. parapsilosis was the most frequent species in children under 15 y (57.1%). All C. parapsilosis isolates were susceptible to anidulafungin, micafungin, flucytosine, amphotericin B, and posaconazole, while 98.5% were susceptible to caspofungin, 97.1% to voriconazole, 95.6% to fluconazole, and 76.5% to itraconazole. CONCLUSIONS: This long-term study showed a slight increase in the incidence of candidemia during the years of the study and a trend towards an increase in C. parapsilosis. Because of its high frequency and intrinsic low susceptibility to echinocandins, the prevalence and susceptibility of C. parapsilosis should be monitored, especially in children.

Molecular identification and antifungal susceptibility of yeast isolates causing fungemia collected in a population-based study in Spain in 2010 and 2011.

We report the molecular identifications and antifungal susceptibilities of the isolates causing fungemia collected in the CANDIPOP population-based study conducted in 29 Spanish hospitals. A total of 781 isolates (from 767 patients, 14 of them having mixed fungemia) were collected. The species found most frequently were Candida albicans (44.6%), Candida parapsilosis (24.5%), Candida glabrata (13.2%), Candida tropicalis (7.6%), Candida krusei (1.9%), Candida guilliermondii (1.7%), and Candida lusitaniae (1.3%). Other Candida and non-Candida species accounted for approximately 5% of the isolates. The presence of cryptic species was low. Compared to findings of previous studies conducted in Spain, the frequency of C. glabrata has increased. Antifungal susceptibility testing was performed by using EUCAST and CLSI M27-A3 reference procedures; the two methods were comparable. The rate of fluconazole-susceptible isolates was 80%, which appears to be a decrease compared to findings of previous studies, explained mainly by the higher frequency of C. glabrata. Using the species-specific breakpoints and epidemiological cutoff values, the rate of voriconazole and posaconazole in vitro resistance was low (<2%). In the case of C. tropicalis, using the EUCAST procedure, the rate of azole resistance was around 20%. There was a correlation between the previous use of azoles and the presence of fluconazole-resistant isolates. Resistance to echinocandins was very rare (2%), and resistance to amphotericin B also was very uncommon. The sequencing of the hot spot (HS) regions from FKS1 or FKS2 genes in echinocandin-resistant isolates revealed previously described point mutations. The decrease in the susceptibility to fluconazole in Spanish isolates should be closely monitored in future studies.

[Streptococcus agalactiae late-onset neonatal infections in Barcelona (1996-2010)]. / La infección neonatal tardía por Streptococcus agalactiae en el área de Barcelona (1996-2010).

OBJETIVE: To study the characteristics and evolution of group B Streptococcus (GBS) late-onset diseases, over a period of 15years in 8hospitals the Barcelona area and analyze the possible impact of prophylactic measures for the prevention of early-onset neonatal infections. METHODS: Retrospective review of all patients diagnosed with late-onset neonatal disease due to GBS from 1996 to 2010. RESULTS: A total of 143 patients were diagnosed. Of these, 51 were born in others hospitals. The overalll incidence was 0.42 per 1000 live births, varying between 0.14‰ in the year 2000 and 0.80‰ in 2009. A slight but sustained tendency of increased risk was observed over the years, 6.9% in the overall disease (with no statistical significance). Sepsis/bacteremia was detected in 63.6% of the newborns, meningitis in 32.8%, and arthritis/osteomyelitis in 3.5%. In cases with known obstetrics dates, 53% of mothers had been colonized by GBS during pregnancy, 53.8% received intrapartum antibiotic prophylaxis, and 41.2% had some obstetric risk factors, particularly premature birth in 35.9%. There was a 2.8% mortality rate in the neonates, and predominant serotypes were III and Ia. CONCLUSIONS: The incidence of GBS late-onset disease has not decreased despite the control practices of early-onset disease, and possibility of this appearing must be taken into account.

Comparison of three statistical methods for establishing tentative wild-type population and epidemiological cutoff values for echinocandins, amphotericin B, flucytosine, and six Candida species as determined by the colorimetric Sensititre YeastOne method.

The Sensititre YeastOne (SYO) method is a widely used method to determine the susceptibility of Candida spp. to antifungal agents. CLSI clinical breakpoints (CBP) have been reported for antifungals, but not using this method. In the absence of CBP, epidemiological cutoff values (ECVs) are useful to separate wild-type (WT) isolates (those without mechanisms of resistance) from non-WT isolates (those that can harbor some resistance mechanisms), which is the goal of any susceptibility test. The ECVs for five agents, obtained using the MIC distributions determined by the SYO test, were calculated and contrasted with those for three statistical methods and the MIC(50) and modal MIC, both plus 2-fold dilutions. The median ECVs (in mg/liter) (% of isolates inhibited by MICs equal to or less than the ECV; number of isolates tested) of the five methods for anidulafungin, micafungin, caspofungin, amphotericin B, and flucytosine, respectively, were as follows: 0.25 (98.5%; 656), 0.06 (95.1%; 659), 0.25 (98.7%; 747), 2 (100%; 923), and 1 (98.5%; 915) for Candida albicans; 8 (100%; 352), 4 (99.2%; 392), 2 (99.2%; 480), 1 (99.8%; 603), and 0.5 (97.9%; 635) for C. parapsilosis; 1 (99.2%; 123), 0.12 (99.2%; 121), 0.25 (99.2%; 138), 2 (100%; 171), and 0.5 (97.2%; 175) for C. tropicalis; 0.12 (96.6%; 174), 0.06 (96%; 176), 0.25 (98.4%; 188), 2 (100%; 209), and 0.25 (97.6%; 208) for C. glabrata; 0.25 (97%; 33), 0.5 (93.9%; 33), 1 (91.9%; 37), 4 (100%; 51), and 32 (100%; 53) for C. krusei; and 4 (100%; 33), 2 (100%; 33), 2 (100%; 54), 1 (100%; 90), and 0.25 (93.4%; 91) for C. orthopsilosis. The three statistical methods gave similar ECVs (within one dilution) and included ≥ 95% of isolates. These tentative ECVs would be useful for monitoring the emergence of isolates with reduced susceptibility by use of the SYO method.

Nocardiosis pulmonar en pacientes con EPOC: características y factores pronósticos / Pulmonary Nocardiosis in Patients with COPD: Characteristics and Prognostic Factors

Introducción: La nocardiosis pulmonar (NP) es una infección grave que afecta principalmente a pacientes inmunodeprimidos y se asocia a una elevada morbimortalidad. En los últimos años se ha detectado un aumento de casos de NP en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Los factores que se asocian a su presencia y determinan su pronóstico son desconocidos. Material y métodos: Estudio retrospectivo de los pacientes con NP y EPOC diagnosticados durante el período 1997-2009 en el Hospital de Sant Pau de Barcelona. Se recogieron datos demográficos, clínicos, microbiológicos y evolutivos. Resultados: Se identificaron 30 pacientes con NP y EPOC. La media (desviación estándar) de edad fue de 76 (7) años, y la de FEV1, del 40 (14)%. El 56,7% presentaba insuficiencia respiratoria crónica y el 51,7% había recibido tratamiento corticoesteroideo sistémico previo al diagnóstico. Los síntomas más frecuentes fueron tos y disnea (90%). En el 60% de los casos se observaron infiltrados alveolares. La especie de Nocardia aislada con mayor frecuencia fue N. cyriacigeorgica (68%). La mortalidad el primer mes fue del 17%, y al año, del 33%. Los factores que se asociaron con mortalidad al año fueron tratamiento corticoesteroideo sistémico previo, antibioticoterapia específica durante menos de 3meses y presencia de neoplasia activa asociada. Conclusiones: La NP puede afectar a pacientes con EPOC moderada y grave y cursa con una elevada mortalidad a corto y medio plazo. El tratamiento corticoesteroideo previo, recibir una terapia antibiótica específica durante menos de 3 meses y la presencia de neoplasia activa son los factores que se asocian a la mortalidad(AU)

Introduction: Pulmonary nocardiosis (PN) is a severe infection with a high morbidity and mortality that mainly affects immunocompromised patients. In recent years, an increase in PN cases has been detected among patients with chronic obstructive pulmonary disease (COPD). The factors that are associated with its presence and determine its prognosis remain unknown. Methods: Retrospective study of COPD patients diagnosed with PN over the period from 1997-2009 at the Hospital de la Santa Creu i Sant Pau, in Barcelona (Spain). Demographic, clinical, microbiological and evolution data were evaluated in all cases. Results: Thirty patients were identified with PN and COPD. Mean age (standard deviation) was 76 (7) years and the mean FEV1 was 40 (14)%. Chronic respiratory failure was observed in 56,7% patients and 51,7% had received systemic corticosteroid therapy previous to the PN diagnosis. The most common symptoms were cough and dyspnea (90%). Alveolar infiltrates were observed in 60% of the cases. The most frequently isolated Nocardia species was N. cyriacigeorgica (68%). The one-month mortality rate was 17%, while the one-year mortality rate was 33%. The factors associated with mortality within the first year included previous systemic corticosteroid treatment, less than three months of specific antibiotic therapy and active associated neoplasm. Conclusions: PN affects patients with moderate-severe COPD and has high short- and mid-term mortality rates. Previous corticosteroid treatment, specific antibiotic therapy for less than 3 months and active neoplasia were factors associated with mortality(AU)

Pulmonary nocardiosis in patients with COPD: characteristics and prognostic factors.

INTRODUCTION: Pulmonary nocardiosis (PN) is a severe infection with a high morbidity and mortality that mainly affects immunocompromised patients. In recent years, an increase in PN cases has been detected among patients with chronic obstructive pulmonary disease (COPD). The factors that are associated with its presence and determine its prognosis remain unknown. METHODS: Retrospective study of COPD patients diagnosed with PN over the period from 1997-2009 at the Hospital de la Santa Creu i Sant Pau, in Barcelona (Spain). Demographic, clinical, microbiological and evolution data were evaluated in all cases RESULTS: Thirty patients were identified with PN and COPD. Mean age (standard deviation) was 76 (7) years and the mean FEV(1) was 40 (14)%. Chronic respiratory failure was observed in 56,7% patients and 51,7% had received systemic corticosteroid therapy previous to the PN diagnosis. The most common symptoms were cough and dyspnea (90%). Alveolar infiltrates were observed in 60% of the cases. The most frequently isolated Nocardia species was N. cyriacigeorgica (68%). The one-month mortality rate was 17%, while the one-year mortality rate was 33%. The factors associated with mortality within the first year included previous systemic corticosteroid treatment, less than three months of specific antibiotic therapy and active associated neoplasm. CONCLUSIONS: PN affects patients with moderate-severe COPD and has high short- and mid-term mortality rates. Previous corticosteroid treatment, specific antibiotic therapy for less than 3 months and active neoplasia were factors associated with mortality.