Abiotrophia spp. and Granulicatella spp. Infective Endocarditis: A Contemporary Perspective.

BACKGROUND: Abiotrophia spp. and Granulicatella spp. are Gram-positive cocci, formerly known as nutritionally variant or deficient Streptococcus. Their role as causative agents of infective endocarditis (IE) is numerically uncertain, as well as diagnostic and clinical management of this infection. The aim of our study is to describe the clinical, microbiological, therapeutic, and prognosis of patients with IE caused by these microorganisms in a large microbiology department. METHODS: Retrospective analysis of all the patients with Abiotrophia spp. and Granulicatella spp. IE registered in our centre in the period 2004-2021. RESULTS: Of the 822 IE in the study period, 10 (1.2%) were caused by Abiotrophia spp. (7) or Granulicatella spp. (3). The species involved were A.defectiva (7), G.adiacens (2) and G.elegans (1). Eight patients were male, their mean age was 46 years and four were younger than 21 years. The most frequent comorbidities were congenital heart disease (4; 40%) and the presence of intracardiac prosthetic material (5; 50%). IE occurred on 5 native valves and 5 prosthetic valve or material. Blood cultures were positive in 8/10 patients, within a mean incubation period of 18.07 hours. In the other two patients, a positive 16SPCR from valve or prosthetic material provided the diagnosis. Surgery for IE was performed in seven patients (70%) and in all cases positive 16S rRNA PCR and sequencing from valve or prosthetic material was demonstrated. Valves and/or prosthetic removed material cultures were positive in four patients. Nine patients received ceftriaxone (4 in monotherapy and 5 in combination with other antibiotics). The mean length of treatment was 6 weeks and IE-associated mortality was 20% at one year follow-up. CONCLUSIONS: Abiotrophia spp. or Granulicatella spp. IE were infrequent but not exceptional in our environment and particularly affected patients with congenital heart disease or prosthetic material. Blood cultures and molecular methods allowed the diagnosis. Most of them required surgery and the associated mortality, in spite of a mean age of 46 years, was high.

[Recurrent Cupriavidus Pauculus catheter-related bacteremia]. / Bacteriemia recurrente relacionada con catéter por Cupriavidus pauculus.

Catheter-related bacteriemia by Cupriavidus spp. is a rare condition with very few cases reported in the literature. Most of them occurred in immunocompromised patients. OBJECTIVE: To report a case of recurrent catheter-related bacteriemia by Cupriavidus pauculus in an immunocompromised infant in order to analyze possible therapeutic options, especially in relation to the need or not for central venous catheter (CVC) removal. CLINICAL CASE: 22-month-old infant with B-cell acute lymphoblas tic leukemia (ALL) in reinduction phase, CVC carrier. He presented to the Emergency Room with fever without focus on examination. Blood tests were performed (without increase of acute phase reactants) and differential blood cultures (peripheral and CVC). He was hospitalized and empirical antibiotic therapy was started with intravenous fourth-generation cephalosporin (cefepime). After 24 hours, blood cultures were positive for Cupriavidus pauculus, growing first in the CVC culture. We maintained cefepime, adding catheter lock therapy with ciprofloxacin. Afterward, the infection was resolved, allowing us to keep the CVC. Seven months later, in the context of fever, Cupriavidus pauculus was again identified in CVC blood culture. We decided this time to remove the catheter, in addition to the administration of intravenous cefepime. The patient has not presented new episodes nine months after de removal of the CVC. CONCLUSION: Catheter-related bacteremia by Cupriavidus is a rare condition in children that usually occurs in immunocompromised patients. Catheter lock therapy associated with systemic antibiotics could be a safe option in patients with difficult CVC re moval. However, if persistent colonization of the CVC is suspected, it may be necessary to remove it.

Prevalence and clinical features of secondary skin lesions in septic patients with bloodstream infections.

Cutaneous manifestations developed in the course of sepsis are poorly documented in the medical literature beyond those related to specific pathogens or classical clinical pictures such as purpura fulminans or ecthyma gangrenosum. The objective of this study was to determine the overall prevalence of sepsis-related skin findings and evaluate their possible impact on the prognosis of septic patients. Single-centre, retrospective study of septic patients with documented bloodstream infections admitted in a tertiary hospital during 2019. Primary skin and soft tissue infections, and non-sepsis-related skin conditions diagnosed during hospital admission were excluded. Unselected sample of 320 episodes of sepsis in 265 patients. Secondary skin lesions were documented in 57 sepsis episodes (17.8%) in 47 patients. Purpura (petechiae/ecchymosis) was the most frequent cutaneous finding in septic patients (35.5%), with non-acral involvement in more than one-third of the episodes (38.5%), followed by skin and soft tissue erythema/oedema (25.8%) and maculopapular rashes (11.3%). Secondary skin lesions occurred more frequently in sepsis of respiratory (p = 0.027) and skin and soft tissue (p = 0.018) origin, as well as in sepsis caused by Pseudomonas aeruginosa and Stenotrophomonas maltophilia (p = 0.001). Mean hospital stay was 38.58 days and sepsis-related mortality 21.1%. Our results suggest that cutaneous involvement in the course of sepsis is frequent, with purpura being the main clinical sign. The semiology described in this study, easily identifiable by non-dermatologists, should alert clinicians to the potential unfavourable course of these patients.

Revisiting nocardiosis at a tertiary care institution: Any change in recent years?

OBJECTIVE: To analyse relevant changes in incidence, clinical and microbiological characteristics of nocardiosis over the last 24 years at the current institution. MATERIALS AND METHODS: The clinical records of patients with nocardiosis (2006-2018) were reviewed and then compared with a previous cohort (1995-2006). Nocardia isolates were identified by 5'-end-16S-rRNA-gene-PCR targeting the first 500 bp of the gene and sequencing. Susceptibility tests were determined by broth microdilution (CLSI guidelines). RESULTS: Forty-two patients (64.3% male) with nocardiosis were evaluated in the recent cohort: 51.2% had COPD, 43.9% were on corticosteroid therapy and 31.7% had cancer. The incidence of nocardiosis varied from 6.3 to 7.1/100,000 admissions (p = 0.62). There was a decrease in HIV patients (27% vs. 4.9%, p = 0.01) and solid organ transplantation (SOT) recipients (18.9% vs. 2 .4%, p = 0.01). Cases with pulmonary involvement had increased (70.3% vs. 90.5%, p = 0.04). Nocardia species were similar but the most common were N. cyriacigeorgica (32.4% vs. 40.5%, p = 0.49) and N. farcinica (24.3% vs. 14.3%, p = 0.39). Antibiotic resistance remained stable: cotrimoxazole (10.8% vs. 5.7%, p = 0.68), imipenem (5.4% vs. 5.6%, p = 1.0); amikacin and linezolid were 100% active. No differences were found in breakthrough nocardiosis (21.6% vs. 9.8%, p = 0.21) or related mortality (21.6% vs. 21.4%, p = 1.0). The multivariate analysis confirmed that nocardiosis caused by N. farcinica is a risk factor for poor outcome (p = 0.045). CONCLUSIONS: Nocardiosis incidence has remained stable. It mainly affected elderly patients with chronic respiratory conditions and those on corticosteroid treatment. Infections in HIV and SOT patients have practically disappeared. Pulmonary involvement remains the most common area to be affected. Nocardiosis caused by N. farcinica is apparently a risk factor for poor clinical outcome.

A retrospective cohort of invasive fusariosis in the era of antimould prophylaxis.

Mould-active prophylaxis is affecting the epidemiology of invasive mycoses in the form of a shift toward less common entities such as fusariosis. We analyze the characteristics of invasive fusariosis and its association to antifungal prophylaxis in a retrospective cohort (2004-2017) from a tertiary hospital in Madrid, Spain. Epidemiological, clinical, microbiological, and antifungal consumption data were retrieved. Isolates were identified to molecular level, and antifungal susceptibility was tested. Eight cases of invasive fusariosis were diagnosed. Three periods were identified according to incidence: <2008 (three cases), 2008-2013 (zero cases), >2014 (five cases). All except one case involved breakthrough fusariosis. During the earliest period, the episodes occurred while the patient was taking itraconazole (two) or fluconazole (one); more recently, while on micafungin (three) or posaconazole (one). Early cases involved acute leukemia at induction/consolidation, recent cases relapsed/refractory disease (P = .029). Main risk factor for fusariosis (62.5%) was prolonged neutropenia (median 44 days). Galactomannan and beta-D-glucan were positive in 37.5% and 100% of cases, respectively. All isolates except F. proliferatum presented high minimal inhibitory concentrations (MICs) against the azoles and lower MIC to amphotericin B. Most patients received combined therapy. Mortality at 42 days was 62.5%. Resolution of neutropenia was associated with survival (P = .048). Invasive fusariosis occurs as breakthrough infection in patients with hematologic malignancy, prolonged neutropenia, and positive fungal biomarkers. Recent cases were diagnosed in a period of predominant micafungin use in patients who had more advanced disease and protracted neutropenia and for whom mortality was extremely high. Resolution of neutropenia was a favorable prognostic factor.

Evaluation of the Alfred™ turbidity monitoring system (Alifax®) following sonication in the diagnosis of central venous catheter colonization.

The conventional diagnostic techniques for catheter colonization (CC) take at least 48 h to yield results. Therefore, new diagnostic procedures that speed up the time necessary for results are needed. Our main objective was to assess the efficacy of the combination of sonication, turbidity monitoring, and MALDI-TOF to detect CC and catheter-related bloodstream infection (C-RBSI). For 1 year, we assessed central venous catheter (CVC) tips that arrived at the microbiology laboratory from adult patients admitted to our institution. CVC tips were cut, inoculated into 2.5 ml of BHI, and sonicated for 1 min. The suspension was then processed using Gram stain, quantitative culture (gold standard), and preincubation on the Alfred™ system. We analyzed the validity values of our new diagnostic approach for prediction of CC and C-RBSI and compared them with those of the gold standard. We collected a total of 167 catheters, 33 (19.8%) of which were colonized. We confirmed 21 episodes of C-RBSI. The distribution of microorganisms in colonized CVCs was as follows: Gram-positive, 68.4%; Gram-negative, 5.3%; and yeasts, 26.3%. The validity values for CC and C-RBSI using the new procedure were as follows: S, 39.4%/61.9%; Sp, 100%/100%; PPV, 100%/100%; and NPV, 87.0%/94.8%. The combination of sonication with a pre-incubation period based on turbidity monitoring using the Alfred™ system followed by MALDI-TOF proved to be a useful tool that was faster than conventional culture for ruling out C-RBSI. Future studies are needed to assess the clinical and economic impact of this diagnostic approach.

MSH2 Gene Point Mutations Are Not Antifungal Resistance Markers in Candida glabrata.

The high rates of antifungal resistance in Candida glabrata may be facilitated by the presence of alterations in the MSH2 gene. We aimed to study the sequence of the MSH2 gene in 124 invasive C. glabrata isolates causing incident episodes of candidemia (n = 81), subsequent candidemia episodes (n = 9), endocarditis (n = 2), and in vitro-generated echinocandin-resistant isolates (n = 32) and assessed its relationship with genotypes, acquisition of antifungal resistance in vivo and in vitro, and patient prognosis. The MSH2 gene was sequenced, and isolates were genotyped using six microsatellite markers and multilocus sequence typing (MLST) based on six housekeeping genes. According to EUCAST, isolates causing candidemia (n = 90) were echinocandin susceptible, and four of them were fluconazole resistant (MIC ≥64 mg/liter). One isolate obtained from a heart valve was resistant to micafungin and anidulafungin (MICs, 2 mg/liter and 1 mg/liter, respectively). MSH2 gene mutations were present in 44.4% of the incident isolates, the most common being V239L. The presence of MSH2 mutations was not correlated with in vitro or in vivo antifungal resistance. Microsatellite and MLST revealed 27 genotypes and 17 sequence types, respectively. Fluconazole-resistant isolates were unrelated. Most MSH2 mutations were found in cluster isolates; conversely, some mutations were found in more than one genotype. No clinical differences, including previous antifungal use, were found between patients infected by wild-type MSH2 gene isolates and isolates with any point mutation. The presence of MSH2 gene mutations in C. glabrata isolates causing candidemia is not correlated with specific genotypes, the promotion of antifungal resistance, or the clinical outcome.

Candida guilliermondii Complex Is Characterized by High Antifungal Resistance but Low Mortality in 22 Cases of Candidemia.

The objectives of our study were to describe the characteristics of patients with Candida guilliermondii candidemia and to perform an in-depth microbiological characterization of isolates and compare them with those of patients with C. albicans candidemia. We described the risk factors and outcomes of 22 patients with candidemia caused by the C. guilliermondii complex. Incident isolates were identified using molecular techniques, and susceptibility to fluconazole, anidulafungin, and micafungin was studied. Biofilm formation was measured using the crystal violet assay (biomass production) and the XTT reduction assay (metabolic activity), and virulence was studied using the Galleria mellonella model. Biofilm formation was compared with that observed for C. albicans The main conditions predisposing to infection were malignancy (68%), immunosuppressive therapy (59%), and neutropenia (18%). Clinical presentation of candidemia was less severe in patients infected by the C. guilliermondii complex than in patients infected by C. albicans, and 30-day mortality was lower in C. guilliermondii patients (13.6% versus 33.9%, respectively; P = 0.049). Isolates were identified as C. guilliermondiisensu stricto (n = 17) and Candida fermentati (n = 5). The isolates produced biofilms with low metabolic activity and moderate biomass. The G. mellonella model showed that C. guilliermondii was less virulent than C. albicans (mean of 6 days versus 1 day of survival, respectively; P < 0.001). Patients with candidemia caused by the C. guilliermondii complex had severe and debilitating underlying conditions. Overall, the isolates showed diminished susceptibility to fluconazole and echinocandins, although poor biofilm formation and the low virulence were associated with a favorable outcome.