Evidence of Fluconazole-Resistant Candida parapsilosis Genotypes Spreading across Hospitals Located in Madrid, Spain and Harboring the Y132F ERG11p Substitution.

We have been monitoring the antifungal resistance in Candida parapsilosis isolates collected from inpatients at Madrid metropolitan area hospitals for the last 3 years. The study aimed to elucidate the presence of fluconazole-resistant C. parapsilosis genotypes in Madrid. From January 2019 to December 2021, a total of 354 C. parapsilosis isolates (n = 346 patients) from blood (76.6%) or intraabdominal samples were collected and genotyped using species-specific microsatellite markers. Antifungal susceptibilities to amphotericin B, the triazoles, micafungin, anidulafungin, and ibrexafungerp were performed according to EUCAST E.Def 7.3.2; the ERG11 gene was sequenced in fluconazole-resistant isolates. A total of 13.6% (n = 48/354) isolates (one per patient) were found to be resistant to fluconazole and non-wild-type to voriconazole but fully susceptible to ibrexafungerp. Resistant isolates were mostly sourced from blood (n = 45/48, 93.8%) and were detected in five hospitals. Two hospitals accounted for a high proportion of resistant isolates (n = 41/48). Resistant isolates harbored either the Y132F ERG11p amino acid substitution (n = 43) or the G458S substitution (n = 5). Isolates harboring the Y132F substitution clustered into a clonal complex involving three genotypes (one genotype accounted for n = 39/43 isolates) that were found in four hospitals. Isolates harboring the G458S substitution clustered into another genotype found in a fifth hospital. C. parapsilosis genotypes demonstrating resistance to fluconazole have been spreading across hospitals in Madrid, Spain. Over the last 3 years, the frequency of isolation of such isolates and the number of hospitals affected is on the rise.

A retrospective validation of different scores of guideline adherence and infectious diseases consultation on candidaemia: The higher, the better.

BACKGROUND: Recently, several scores to quantify compliance with the guidelines in candidaemia management (EQUAL, GEMICOMED, Valerio) have been developed. Evidence supporting the association of these scores to the prognosis is scarce. We aim to evaluate the performance of these candidaemia guideline adherence scores to predict candidaemia outcome. METHODS: We recorded retrospectively data from candidaemia episodes (January 2017-December 2018). We analysed adherence to guidelines for candidaemia management according to EQUAL, GEMICOMED and Valerio scores, and we correlated those to outcome. RESULTS: Fifty-four first episodes of candidaemia were retrieved. Five patients who died in the first 48 hours after blood cultures were not included. Thirty-day mortality in evaluable patients was 18.4%. Median adherence to guidelines according to EQUAL score was 17 (interquartile range [IQR]: 15-19), and according to GEMICOMED was 86% (IQR: 72.5%-100%). According to Valerio score, adequacy of antifungal prescription was 8.5/10 (SD: 1.9). A cut-off of ≥17 for EQUAL or compliance >70% for GEMICOMED was associated with inferior 30-day mortality (7.1% vs 33.3%, P = .028 and 7.9% vs 54.5%, P = .002, respectively). Infectious diseases (ID) evaluated cases obtained a better EQUAL score (>17; 82.1% vs 42.9%, P = .006), had inferior 30-day mortality (9.4% vs 35.3%, P = .049) and a better antifungal prescription adequacy (Valerio score 9.0 vs 7.5, P = .011). CONCLUSION: Adherence to guidelines for candidaemia management evaluated by means of EQUAL and GEMICOMED score was associated with a decreased 30-day mortality. Adequacy of antifungal prescription can be ameliorated. ID consultation improved guideline adherence and was associated with decreased 30-day mortality.

Effective definition of low humoral response to Clostridioides difficile infection.

BACKGROUND: Determination of the humoral response to Clostridioides difficile (CD) toxins could be of great value in the management of patients with CD infection (CDI). METHODS: A prospective study was conducted on the clinical characteristics and humoral response in patients with CDI. Determination of ELISA IgG CD anti-toxin B (tgcBiomics, Germany) was performed. The following dilutions were planned for each patient, 1:100, 1: 200, 1: 400, 1: 800: 1: 1600. A significant concentration of antibody was considered to be present in each dilution if an optical density 0.2 units higher than the negative control of the technique was evident. RESULTS: Eighty-five patients were included during the study period, November 2018-February 2020. The median age was 73 years (interquartile range: 62.5-85 years), with female predominance (45 patients, 52.9%). Thirty-nine patients (45.9%) had a severe infection. Seven patients (8.2%) had suffered an episode of CDI in the previous three months. Seventeen patients (20%) had one or more recurrent episodes during the three-month follow-up: No patient died during admission or required surgery for severe-complicated infection. The incidence of recurrence in patients with no antibody detected at 1:400 dilution was 25.4% (16 patients) while it was 4.3% (one patient) in patients with antibody present at that dilution (p = 0.03). Liver cirrhosis was associated with higher humoral response against CD. CONCLUSIONS: Antibodies IgG CD anti-toxin B detection at a dilution of 1:400, using a B ELISA technique, effectively identified patients at increased risk of recurrence. This information could help assist in the management of patients.

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.

Epidemiology and prognosis of candidaemia in elderly patients.

The aim of the study was to analyse the epidemiology and prognosis of candidaemia in elderly patients. We performed a comparison of clinical presentation of candidaemia according to age and a study of hazard factors within a prospective programme performed in 29 hospitals. One hundred and seventy-six episodes occurred in elderly patients (>75 years), 227 episodes in middle-aged patients (61-75 years) and 232 episodes in younger patients (16-60 years). Central venous catheter, parenteral nutrition, neutropenia, immunosuppressive therapy and candidaemia caused by Candida parapsilosis were less frequent in elderly patients. These patients received inadequate antifungal therapy (57.3%) more frequently than middle-aged and younger patients (40.5% P < .001). Mortality during the first week (20%) and 30 days (42%) was higher in elderly patients. The variables independently associated with mortality in elderly patients during the first 7 days were acute renal failure (OR: 2.64), Pitt score (OR: 1.57) and appropriate antifungal therapy (OR: 0.132). Primary candidaemia (OR: 2.93), acute renal failure (OR: 3.68), Pitt score (OR: 1.38), appropriate antifungal therapy (OR: 0.3) and early removal of the central catheter (OR: 0.47) were independently associated with 30-day mortality.In conclussion, inadequate antifungal treatment is frequently prescribed to elderly patients with candidaemia and is related with early and late mortality.

Risk factors, clinical presentation and prognosis of mixed candidaemia: a population-based surveillance in Spain.

The low incidence of mixed candidaemia (MC) may have precluded a better knowledge of its clinical presentation. The aim of the study was to analyse the risk factors, clinical presentation and prognosis of MC episodes. A comparison between MC and monomicrobial candidaemia within a prospective programme on candidaemia was performed in 29 hospitals between April 2010 and May 2011. In fifteen episodes of candidaemia corresponding to 15 patients, out of 752, two species of Candida (1.9%) were isolated. MC was more frequent in patients with HIV infection (12%, P = 0.038) and those admitted due to extensive burns (23%, P = 0.012). The Candida species most frequently identified in MC were C. albicans 12 patients (40%), C. glabrata seven patients (23.3%) and C. parapsilosis six patients (20%). Early mortality was higher (nine patients, 60%) in patients with MC than in patients with MMC (223 patients, 30.3%, P = 0.046). In conclusion, MC was was independently associated with increased mortality even after considering other prognostic factors. MC is an infrequent event that is more common in HIV infection and in patients suffering from burns, and is associated with increased mortality.

Characteristics of Clostridium difficile infection in patients with discordant diagnostic test results.

BACKGROUND: Clinical features of Clostridium difficile infection (CDI) cases diagnosed by detection of polymerase chain reaction (PCR), with negative toxin enzyme immunoassay results (EIA) have not been fully elucidated. The purpose of this study was to determine the magnitude of CDI patients who had negative EIA toxin determinations but positive PCR tests, and their differences in clinical presentation. METHODS: We performed a retrospective study comparing the clinical features of CDI cases detected by EIA (toxins A + B) with cases detected by PCR (toxin negative, PCR positive) over a 16-month period. Only patients with an initial Clostridium difficile infection episode that fulfilled a standardized definition were included. RESULTS: During the study period, 107 episodes of CDI were detected. Seventy-four patients (69%) had positive glutamate dehydrogenase (GDH) antigen and EIA determinations (EIA positive patients). Thirty-three patients (31%) had GDH positive, negative toxin EIA and positive PCR determination (PCR positive patients). PCR positive patients were younger, 57 (27) years (mean [SD]), than EIA positive patients, 71 (16) years, (p < 0.001). Fewer PCR positive patients were receiving proton pump inhibitors (21 patients, 64%) than EIA positive patients (61 patients, 82%, p = 0.034). The clinical presentation was similar in both groups. In the multivariate analysis, lower age was identified as the only independent variable associated with PCR positive patients. CONCLUSIONS: One third of Clostridium difficile infection patients present negative toxin EIA and PCR positive tests. Performing PCR determination after the negative EIA test is more relevant in younger patients.

Risk factors for Clostridium difficile diarrhea in patients with inflammatory bowel disease.

BACKGROUND: Despite the growing incidence of Clostridium difficile diarrhea (CCD) in patients with inflammatory bowel disease (IBD), little is known about the associated risk factors. METHOD: A retrospective study comparing cases of CCD in patients with IBD to IBD carriers who did not develop CCD. A comparison was also made with patients who developed CCD but did not suffer IBD. RESULTS: Three cases (20%) with IBD and CCD had received antibiotics during the previous three months versus none of the controls (IBD without CCD, p = 0.22). Ten cases (67%) received treatment with proton pump inhibitors (PPIs) versus 2 (13%) in the control group (IBD without CCD, p = 0.001). Seven cases underwent colonoscopy and pseudomembranes were seen in one (14%). Fourteen (93%) patients demonstrated a favourable response to metronidazole. Patients with IBD and CCD presented with younger age (36 ± 10 years), a higher degree of community-acquired infection (13 patients, 87%), immunosuppressive treatment (7 patients, 47%) and less patients had received previous antibiotic treatment (3 patients, 20%) than those with CCD without IBD. The proportion of patients who received treatment with PPIs was similar (66% and 80%, respectively p = 0.266). CONCLUSIONS: CCD in IBD carriers affects younger patients, the majority are community acquired (less nosocomial) and it is more related to previous treatment with PPIs than with the antibiotic treatment. Clinical evolution is also favourable.

Gonococcal endocarditis: a case report and review of the literature.

A 59-year-old Caucasian male presented with progressive dyspnea, arthralgias and fever for three days. A diastolic regurgitation murmur was detected in the aortic area. A transesophageal echocardiograph showed several vegetations and severe aortic regurgitation. Blood cultures yielded Neisseria gonorrhoeae beta-lactamase negative. The patient had not noticed any urogenital discomfort or urethral discharge. The patient successfully underwent surgery for septal abscess debridement. The patient received ceftriaxone 2 g bid for eight weeks and the clinical follow-up was uneventful. The review of the literature revealed a total of the 38 additional cases reported between 1980 and the present. The majority of the patients were young, male and with native valve involvement. There has been a clear tendency for left-sided valve involvement (especially in the aortic valve). All valve cultures were reported negative despite, in most cases, the marked tissue destruction. Polymerase chain reaction was performed in two patients and positive results were shown in both. Cultures of exudates from other locations were negative in most cases. One striking fact is the high proportion of patients who underwent surgery (72 %). Information regarding antibiotic sensitivity was available in 28 cases, with penicillin resistance reported in six patients (21 %) and intermediate sensitivity in four patients (14 %). Resistance to ciprofloxacin was reported in two cases (7 %). A rapid increase and distribution of isolates resistant to third generation cephalosporins have been recently detected. The mortality is high, particularly taking into account that most were young patients who had not presented previous heart disease.

Characterizing carbapenemase-producing Escherichia coli isolates from Spain: high genetic heterogeneity and wide geographical spread.

Introduction: Carbapenemase-Producing Escherichia coli (CP-Eco) isolates, though less prevalent than other CP-Enterobacterales, have the capacity to rapidly disseminate antibiotic resistance genes (ARGs) and cause serious difficult-to-treat infections. The aim of this study is phenotypically and genotypically characterizing CP-Eco isolates collected from Spain to better understand their resistance mechanisms and population structure. Methods: Ninety representative isolates received from 2015 to 2020 from 25 provinces and 59 hospitals Spanish hospitals were included. Antibiotic susceptibility was determined according to EUCAST guidelines and whole-genome sequencing was performed. Antibiotic resistance and virulence-associated genes, phylogeny and population structure, and carbapenemase genes-carrying plasmids were analyzed. Results and discussion: The 90 CP-Eco isolates were highly polyclonal, where the most prevalent was ST131, detected in 14 (15.6%) of the isolates. The carbapenemase genes detected were bla OXA-48 (45.6%), bla VIM-1 (23.3%), bla NDM-1 (7.8%), bla KPC-3 (6.7%), and bla NDM-5 (6.7%). Forty (44.4%) were resistant to 6 or more antibiotic groups and the most active antibiotics were colistin (98.9%), plazomicin (92.2%) and cefiderocol (92.2%). Four of the seven cefiderocol-resistant isolates belonged to ST167 and six harbored bla NDM. Five of the plazomicin-resistant isolates harbored rmt. IncL plasmids were the most frequent (45.7%) and eight of these harbored bla VIM-1. bla OXA-48 was found in IncF plasmids in eight isolates. Metallo-ß-lactamases were more frequent in isolates with resistance to six or more antibiotic groups, with their genes often present on the same plasmid/integron. ST131 isolates were associated with sat and pap virulence genes. This study highlights the genetic versatility of CP-Eco and its potential to disseminate ARGs and cause community and nosocomial infections.

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients.

OBJECTIVES: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSION: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

Emergence of OXA-48-producing Klebsiella pneumoniae and the novel carbapenemases OXA-244 and OXA-245 in Spain.

OBJECTIVES: To describe the molecular and population-level characterization of a selected group of OXA-48-like-producing Klebsiella pneumoniae isolates collected in Spain between January 2011 and May 2012. METHODS: During the study period, 151 OXA-48-like-producing K. pneumoniae isolates were collected from 10 hospitals in six different Spanish regions. From these, a representative sample of 21 isolates that caused hospital outbreaks and single infections was selected for further in-depth analysis. Molecular epidemiology was investigated using PFGE and multilocus sequence typing (MLST). Resistance genes were characterized by PCR and sequencing. Plasmids carrying bla(OXA-48-like) were studied by PFGE with S1 nuclease digestion. RESULTS: All 21 isolates had ertapenem MICs ≥ 1 mg/L, but 47.6% remained susceptible to imipenem and meropenem; bla(OXA-48) was identified in 19 isolates (90.5%) and the novel bla(OXA-244) and bla(OXA-245) genes were detected in 1 isolate each. With one exception, all isolates that contained bla(OXA-48-like) also contained bla(CTX-M-15). PFGE typing revealed six clusters comprising isolates that belonged to MLST types ST11, ST16, ST392, ST405, ST437 and ST663, respectively. Two main clusters were identified: PFGE cluster 1 (12 isolates, belonging either to ST405 or ST663, from seven hospitals), and PFGE cluster 2 (4 ST16 isolates from two hospitals). Six of seven donor isolates conjugated successfully; bla(OXA-48-like) (but not bla(CTX-M-15)) was carried on ≈ 60 kb Inc L/M plasmids. CONCLUSIONS: Multidrug-resistant K. pneumoniae producing OXA-48-like carbapenemase are emerging as important pathogens in Spain due to intra- and inter-hospital, clonal and non-clonal dissemination.

[Microbiological diagnosis of intra-abdominal infections]. / Diagnóstico microbiológico de las infecciones intraabdominales.

Intra-abdominal infections represent a large and wide group of diseases which include intra- and retro-peritoneal infections. Some of them could be defined as uncomplicated, where the infectious process is limited to the organ or tissue of origin (appendicitis, diverticulitis, cholecystitis…). Complications occur when the infection spreads to the peritoneum, triggering localised peritonitis and abdominal abscesses. Most intra-abdominal infections are due to perforation or inflammation of the intestinal wall. The microorganisms that cause these infections come from the gastrointestinal flora, and therefore produce polymicrobial infections mixed with a predominance of anaerobic bacteria. Microbiological diagnosis is essential to determine the aetiology and the susceptibility of antimicrobial agents of the microorganism involved, especially in nosocomial infections or in community infections in predisposed patients due to increasing bacterial resistance to antimicrobial agents, multidrug resistance and fungal involvement. Despite the advances in microbiological diagnosis, in the case of intra-abdominal infections it still remains direct, being based on stains and cultures, the most notable progress is the introduction of mass spectrometry (MALDI-TOF) for the rapid identification of the pathogens involved. This review will provide recommendations on the collection, transport and microbiological processing of clinical specimens. Comments on the pathogenesis, clinical and microbiological diagnosis of peritonitis primary, secondary, tertiary and peritonitis (and other infections) associated with peritoneal dialysis, intra-abdominal abscesses (intraperitoneal, retroperitoneal and visceral), biliary tract infections, appendicitis and diverticulitis are also presented.

Sequential oral antibiotic in uncomplicated Staphylococcus aureus bacteraemia: a propensity-matched cohort analysis.

OBJECTIVES: We aimed to analyse the efficacy and safety of oral sequential therapy (OST) in uncomplicated Staphylococcus aureus bacteraemia (SAB). METHODS: Single-centre observational cohort at a tertiary hospital in Spain, including all patients with the first SAB episode from January 2015 to December 2020. We excluded patients with complicated SAB and those who died during the first week. Patients were classified into the OST group (patients who received oral therapy after initial intravenous antibiotic therapy [IVT]), and IVT group (patients who received exclusively IVT). We performed a propensity-score matching to balance baseline differences. The primary composite endpoint was 90-day mortality or microbiological failure. Secondary endpoints included 90-day SAB relapse. RESULTS: Out of 407 SAB first episodes, 230 (56.5%) were included. Of these, 112 (n = 48.7%) received OST and 118 (51.3%) IVT exclusively. Transition to oral therapy was performed after 7 days (interquartile range, 4-11). The primary endpoint occurred in 10.7% (11/112) in OST vs. 30.5% (36/118) in IVT (p < 0.001). SAB relapses occurred in 3.6% (4/112) vs. 1.7% (2/118) (p 0.436). None of the deaths in OST were related to SAB or its complications. After propensity-score matching, the primary endpoint was not more frequent in the OST group (relative risk, 0.42; 95% CI, 0.22-0.79). Ninety-day relapses occurred similarly in both groups (relative risk, 1.35; 95% CI, 0.75-2.39). DISCUSSION: After an initial intravenous antibiotic, patients with uncomplicated SAB can safely be switched to oral antibiotics without apparent adverse outcomes. This strategy could save costs and complications of prolonged hospital stays. Prospective randomized studies are needed.

Faecal Microbiota Transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice.

INTRODUCTION: Faecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile infection (CDI). The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting. METHODS: Retrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the faecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhoea in the first 72 h after the procedure with no relapse within the following 8 weeks after the therapy was started. RESULTS: 15 FMT were performed in 13 patients. Median age was 79 years (range: 40-98 years); being 60% women and 33.3% depedent persons. The indication for FMT was recurrent CDI in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the FMT was effective in 11 of 13 patients (84.61%; 95% CI; 54.55-98.07). Time until resolution of symptoms was less than 48 h in all cases. Post-transplant follow-up was 25.66 ±â€¯17.5 months. No significant short or long-term complications were recorded at follow-up. CONCLUSION: TMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.

Breakthrough invasive fungal infection among patients with haematologic malignancies: A national, prospective, and multicentre study.

OBJECTIVES: We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies. METHODS: BtIFI in patients with ≥ 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions. RESULTS: 121 episodes of BtIFI were documented, of which 41 (33.9%) were proven; 53 (43.8%), probable; and 27 (22.3%), possible. The most frequent prior antifungals included posaconazole (32.2%), echinocandins (28.9%) and fluconazole (24.8%)-mainly for primary prophylaxis (81%). The most common haematologic malignancy was acute leukaemia (64.5%), and 59 (48.8%) patients had undergone a hematopoietic stem-cell transplantation. Invasive aspergillosis, principally caused by non-fumigatus Aspergillus, was the most frequent BtIFI with 55 (45.5%) episodes recorded, followed by candidemia (23, 19%), mucormycosis (7, 5.8%), other moulds (6, 5%) and other yeasts (5, 4.1%). Azole resistance/non-susceptibility was commonly found. Prior antifungal therapy widely determined BtIFI epidemiology. The most common cause of BtIFI in proven and probable cases was the lack of activity of the prior antifungal (63, 67.0%). At diagnosis, antifungal therapy was mostly changed (90.9%), mainly to liposomal amphotericin-B (48.8%). Overall, 100-day mortality was 47.1%; BtIFI was either the cause or an essential contributing factor to death in 61.4% of cases. CONCLUSIONS: BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceedingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used.

Nosocomial outbreak of VIM-1-producing Klebsiella pneumoniae isolates of multilocus sequence type 15: molecular basis, clinical risk factors, and outcome.

We study the epidemiology, molecular basis, clinical risk factors, and outcome involved in the clonal dissemination of VIM-1-producing Klebsiella pneumoniae isolates in the hospital setting. All patients infected/colonized by carbapenem-nonsusceptible K. pneumoniae (CNSKP) in 2009 were included. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Antibiotic resistance genes were analyzed by PCR and sequencing. Plasmids were studied by PFGE with S1 nuclease digestion and for incompatibility group by a PCR-based replicon typing scheme. Risk factors associated with CNSKP colonization/infection were assessed by an observational case-control study. All 55 patients studied were infected (n = 28) or colonized (n = 27) by VIM-1-producing K. pneumoniae. All but one acquired isolates of a single clone (PFGE cluster 1 [C1], sequence type 15 [ST15]), while another clone (PFGE C2, ST340) was detected in four patients. C1 isolates also produced the new extended-spectrum ß-lactamase SHV-134. bla(VIM-1) was carried in a class 1 integron and an untypeable plasmid of ∼50 bp. The number of days that the patient received mechanical ventilation, the use of parenteral nutrition, previous treatment with linezolid, and treatment with extended-spectrum cephalosporins for more than 7 days were detected to be independent risk factors for CNSKP acquisition. The VIM-1-producing K. pneumoniae ST15 clone has a high capacity to spread among intensive care unit patients with severe underlying conditions. A high rate of associated mortality and great difficulty in controlling the spread of this clone, without permanent behavioral changes in the personnel, were observed.

Unreliability of Clinical Prediction Rules to Exclude without Echocardiography Infective Endocarditis in Staphylococcus aureus Bacteremia.

BACKGROUND: It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB) without an echocardiogram evaluation, either transthoracic (TTE) and/or transesophageal (TEE). Our primary purpose was to test the usefulness of PREDICT, POSITIVE, and VIRSTA scores to rule out IE without echocardiography. Our secondary purpose was to evaluate whether not performing an echocardiogram evaluation is associated with higher mortality. METHODS: We conducted a unicentric retrospective cohort including all patients with a first SAB episode from January 2015 to December 2020. IE was defined according to modified Duke criteria. We predefined threshold cutoff points to consider that IE was ruled out by means of the mentioned scores. To assess 30-day mortality, we used a multivariable regression model considering performing an echocardiogram as covariate. RESULTS: Out of 404 patients, IE was diagnosed in 50 (12.4%). Prevalence of IE within patients with negative PREDICT, POSITIVE, and VIRSTA scores was: 3.6% (95% CI 0.1-6.9%), 4.9% (95% CI 2.2-7.7%), and 2.2% (95% CI 0.2-4.3%), respectively. Patients with negative VIRSTA and negative TTE had an IE prevalence of 0.9% (95% CI 0-2.8%). Performing an echocardiogram was independently associated with lower 30-day mortality (OR 0.24 95% CI 0.10-0.54, p = 0.001). CONCLUSION: PREDICT and POSITIVE scores were not sufficient to rule out IE without TEE. In patients with negative VIRSTA score, it was doubtful if IE could be discarded with a negative TTE. Not performing an echocardiogram was associated with worse outcomes, which might be related to presence of occult IE. Further studies are needed to assess the usefulness of clinical prediction rules in avoiding echocardiographic evaluation in SAB patients.

Impact of the COVID-19 Pandemic on the Clinical Profile of Candidemia and the Incidence of Fungemia Due to Fluconazole-Resistant Candida parapsilosis.

Severely ill COVID-19 patients are at high risk of nosocomial infections. The aim of the study was to describe the characteristics of candidemia during the pre-pandemic period (January 2019−February 2020) compared to the pandemic period (March 2020−September 2021). Antifungal susceptibilities were assessed using the EUCAST E.Def 7.3.2 broth dilution method. Fluconazole-resistant C. parapsilosis isolates (FRCP) were studied for sequencing of the ERG11 gene. The incidence of candidemia and C. parapsilosis bloodstream infection increased significantly in the pandemic period (p = 0.021). ICU admission, mechanical ventilation, parenteral nutrition and corticosteroids administration were more frequent in patients with candidemia who had been admitted due to COVID-19. Fifteen cases of FRCP fungemia were detected. The first case was recorded 10 months before the pandemic in a patient transferred from another hospital. The incidence of FRCP in patients admitted for COVID-19 was 1.34 and 0.16 in all other patients (p < 0.001). ICU admission, previous Candida spp. colonization, arterial catheter use, parenteral nutrition and renal function replacement therapy were more frequent in patients with candidemia due to FRCP. All FRCP isolates showed the Y132F mutation. In conclusion, the incidence of candidemia experienced an increase during the COVID-19 pandemic and FRCP fungemia was more frequent in patients admitted due to COVID-19.