Cutibacterium species valvular and cardiac device-related infective endocarditis: contemporary data from the GAMES prospective cohort (2008-2023).

BACKGROUND: Information on infective endocarditis (IE) caused by Cutibacterium spp. is limited and new Duke-ISCVID criteria have not yet been properly assessed. We examined clinical characteristics, outcomes and performance of diagnostic tests for Cutibacterium valvular and cardiac implantable electronic device-related IE (CIED-IE). METHODS: Data corresponding to all episodes of Cutibacterium IE recorded from 2008 to 2023 in a prospective national cohort including 46 Spanish hospitals were examined. Possible IE cases were reassessed using the new criteria. The sensitivity of blood cultures, valvular and CIED cultures, and PCR of the 16SrRNA gene and sequencing (16SPCR) was evaluated. RESULTS: There were 67/6,692 (1%) episodes of IE caused by Cutibacterium spp., 85% affecting men. Of these, 50 were valve-related (45 prosthetic, 5 native) and 17 CIED-related. The new criteria identified 8 additional cases and reclassified 15 as definite IE. Intracardiac complications (abscess, pseudoaneurysm, perforation or intracardiac fistula) occurred in 23/50 (46%) valvular IE episodes, leading to 18% mortality, and up to 40% mortality if surgery was indicated but could not be performed. All CIED-IE cases underwent device removal and no deaths were recorded. Positive diagnosis rates for blood cultures, valve/device cultures and 16SPCR were 52%, 70% and 82%, respectively. CONCLUSION: Cutibacterium IE is a rare yet potentially life-threatening condition that warrants a high index of suspicion in men with endovascular prosthetic material. The new Duke-ISCVID criteria and molecular techniques are useful for its diagnosis. Considering a significant complication rate, cardiac surgery and removal of CIEDs play a key role in reducing mortality.

Use of oxazolidinones (linezolid or tedizolid) for the treatment of breast infections. A case series from a tertiary referral hospital.

OBJECTIVES: Mastitis is mainly caused by Gram-positive bacteria and usually involves treatment with beta-lactam antibiotics and clindamycin. Oxazolidinones show good results in the treatment of skin and soft tissue infections (SSTIs) due to its pharmacokinetic characteristics. We aimed to describe clinical characteristics and outcomes of patients who received oxazolidinones for the treatment of SSTIs of the mammary tissue. METHODS: Retrospective single-centre study of patients with a diagnosis of breast infection who received treatment with oxazolidinones as initial or salvage therapy between September 2016 and November 2022. Patients were identified through the pharmacy database. The primary outcome was clinical cure. RESULTS: Twenty-nine patients received oxazolidinones: 27 received linezolid and 2 tedizolid. Median age was 41 years (IQR 31.0-56.5) and 28 patients were female. Ten patients (35%) had a history of breast cancer, while three (10%) had an immunosuppressive condition. Microbiological isolation was obtained in 24 individuals (83%). Predominant isolations were methicillin-resistant Staphylococcus aureus (8, 28%) and methicillin-susceptible S. aureus (7, 24%). Twenty-four patients (83%) received oxazolidinones as a salvage therapy, with a median duration of 14 days (IQR 10-17). Clinical cure was achieved in 24 patients (83%), while 4 relapsed after a median of 15 days (IQR 4-34). One was lost to follow-up. Three patients (10%) were taking selective serotonin reuptake inhibitors, and one of them concurrently received linezolid for 4 days with no adverse events recorded. Cytopenia during treatment was observed in 2/12 individuals. Oxazolidinones allowed hospital discharge in 11/13 hospitalized patients. CONCLUSIONS: Oxazolidinones could be considered as an alternative for treating breast infections.

Antibiotic Efficacy against Methicillin-Susceptible Staphylococcus aureus Biofilms on Synthetic and Biological Vascular Grafts.

OBJECTIVE: To compare the efficacy of five antibiotics against methicillin-susceptible Staphylococcus aureus (MSSA) biofilms on the surface of four vascular grafts. METHODS: In vitro study of two clinical MSSA strains (MSSA2 and MSSA6) and four vascular grafts (Dacron, Dacron-silver-triclosan, Omniflow-II, and bovine pericardium). After a 24-hour incubation period, the graft samples were divided into six groups: growth control (no treatment), ciprofloxacin 4.5mg/L, cloxacillin 100 mg/L, dalbavancin 300 mg/L, daptomycin 140 mg/L, and linezolid 20 mg/L. Quantitative cultures were obtained and results expressed as log10 colony-forming units per milliliter (CFU/mL). Analysis of variance was performed to compare biofilm formation between the different groups. RESULTS: Mean ± SD MSSA2 count on the growth control Dacron graft was 10.05 ± 0.31 CFU/mL. Antibiotic treatment achieved a mean reduction of 45%; ciprofloxacin was the most effective antibiotic (64%). Baseline MSSA2 counts were very low on the Dacron-silver-triclosan (0.50 ± 1.03 CFU/mL) and Omniflow-II (0.33 ± 0.78 CFU/mL) grafts. On the bovine pericardium patch, the count was 9.87 ± 0.50 CFU/mL, but this was reduced by a mean of 45% after antibiotic treatment (61% for ciprofloxacin). Mean MSSA6 count on the growth control Dacron graft was 9.63 ± 0.53 CFU/mL. Antibiotics achieved a mean reduction of 48%, with ciprofloxacin performing best (67% reduction). Baseline MSSA6 count on the Dacron-silver-triclosan graft was 8.54 ± 0.73 CFU/mL. Antibiotics reduced biofilm formation by 72%; cloxacillin was the most effective treatment (86%). The MSSA6 count on the untreated Omniflow-II graft was 1.17 ± 1.52 CFU/mL. For the bovine pericardium patch, it was 8.98 ± 0.67 CFU/mL. Mean reduction after antibiotic treatment was 46%, with cloxacillin achieving the greatest reduction (68%). CONCLUSION: In this in vitro study, ciprofloxacin and cloxacillin performed best at reducing biofilms formed by clinical MSSA strains on the surface of biological and synthetic vascular grafts.

Impact of Intermediate Susceptibility to Penicillin on Antimicrobial Treatment and Outcomes of Endocarditis Caused by Viridans and Gallolyticus Group Streptococci.

BACKGROUND: Evidence supporting combination treatment with a beta-lactam plus an aminoglycoside (C-BA) for endocarditis caused by viridans and gallolyticus group streptococci (VGS-GGS) with intermediate susceptibility to penicillin (PENI-I) is lacking. We assessed the clinical characteristics and outcomes of PEN-I VGS-GGS endocarditis and compared the effectiveness and safety of C-BA with third-generation cephalosporin monotherapy. METHODS: Retrospective analysis of prospectively collected data of a cohort of definite endocarditis caused by penicillin-susceptible and PENI-I VGS-GGS (penicillin minimum inhibitory concentration ranging from 0.25 to 2 mg/L) between 2008 and 2018 in 40 Spanish hospitals. We compared cases treated with monotherapy or with C-BA and performed multivariable analyses of risk factors for in-hospital and 1-year mortality. RESULTS: A total of 914 consecutive cases of definite endocarditis caused by VGS-GGS with complete or intermediate susceptibility to penicillin were included. A total of 688 (75.3%) were susceptible to penicillin and 226 (24.7%) were PENI-I. Monotherapy was used in 415 (45.4%) cases (cephalosporin in 331 cases) and 499 (54.6%) cases received C-BA. In-hospital mortality was 11.9%, and 190 (20.9%) patients developed acute kidney injury. Heart failure (odds ratio [OR]: 6.06; 95% confidence interval [CI]: 1.37-26.87; P = .018), central nervous system emboli (OR: 9.83; 95% CI: 2.17-44.49; P = .003) and intracardiac abscess (OR: 13.47; 95% CI: 2.24-81.08; P = .004) were independently associated with in-hospital mortality among PEN-I VGS-GGS cases, while monotherapy was not (OR: 1.01; 95% CI: .26-3.96; P = .982). CONCLUSIONS: Our findings support the use of cephalosporin monotherapy in PEN-I VGS-GGS endocarditis in order to avoid nephrotoxicity without adversely affecting patient outcomes.

Ceftazidime-Avibactam plus Aztreonam for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria.

This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing Gram-negative bacillus (GNB) infections. The bacteria isolated were Enterobacterales in 22 patients and Pseudomonas aeruginosa in 2. Sixteen out of 19 isolates showed synergistic activity. Two patients presented clinical failure at day 14, and the 30-day mortality was 17% (4/24). CZA/ATM could be considered an alternative therapy for VIM-type-producing GNB infections.

Empirical use of ß-lactam/ß-lactamase inhibitor combinations does not increase mortality compared with cloxacillin and cefazolin in methicillin-susceptible Staphylococcus aureus bacteraemia: a propensity-weighted cohort study.

OBJECTIVES: To evaluate the effectiveness of empirical therapy with ß-lactam/ß-lactamase inhibitor combinations (BL/BLICs) for MSSA bacteraemia. METHODS: We conducted a post hoc analysis of all adult patients with MSSA bacteraemia who were hospitalized at a Spanish university hospital between 2013 and 2018. We compared 30 day mortality among patients receiving initial therapy with BL/BLICs (de-escalated to cloxacillin or cefazolin within 96 h) versus cloxacillin or cefazolin, using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. RESULTS: We evaluated 373 patients with MSSA bacteraemia. Among them, 198 patients met the eligibility criteria, including 127 patients in the BL/BLICs group and 71 patients in the cloxacillin/cefazolin group. Patients in the BL/BLICs group had a higher Charlson comorbidity index (median, 2 [IQR, 1-4.5] versus 2 [IQR, 0-4]); an increased proportion of high-risk sources (i.e. endocarditis, respiratory sources and bacteraemia of unknown origin [34.6% versus 18.3%]); and an earlier start of antibiotic treatment (median, 0 days [IQR, 0-0] versus 1 day [IQR, 1-2]). Thirty day mortality did not significantly differ between the BL/BLICs and the cloxacillin/cefazolin groups (27 patients [21.3%] versus 13 patients [18.3%]; IPTW-adjusted OR = 0.53 [95% CI, 0.18-1.51]). For secondary outcomes, 7 day mortality and 90 day relapse were not statistically different between study groups (8.7% versus 5.6% [P = 0.62] and 6.2% versus 3.8% [P = 0.81], respectively). CONCLUSIONS: BL/BLICs might be an effective empirical treatment for MSSA bacteraemia when de-escalated to cloxacillin or cefazolin within 96 h from the index blood culture.

Infective endocarditis in pregnant women without intravenous drug use: a multicentre retrospective case series.

OBJECTIVES: To describe the clinical features and outcomes of infective endocarditis (IE) in pregnant women who do not inject drugs. METHODS: A multinational retrospective study was performed at 14 hospitals. All definite IE episodes between January 2000 and April 2021 were included. The main outcomes were maternal mortality and pregnancy-related complications. RESULTS: Twenty-five episodes of IE were included. Median age at IE diagnosis was 33.2 years (IQR 28.3-36.6) and median gestational age was 30 weeks (IQR 16-32). Thirteen (52%) patients had no previously known heart disease. Sixteen (64%) were native IE, 7 (28%) prosthetic and 2 (8%) cardiac implantable electronic device IE. The most common aetiologies were streptococci (n = 10, 40%), staphylococci (n = 5, 20%), HACEK group (n = 3, 12%) and Enterococcus faecalis (n = 3, 12%). Twenty (80%) patients presented at least one IE complication; the most common were heart failure (n = 13, 52%) and symptomatic embolism other than stroke (n = 4, 16%). Twenty-one (84%) patients had surgery indication and surgery was performed when indicated in 19 (90%). There was one maternal death and 16 (64%) patients presented pregnancy-related complications (11 patients ≥1 complication): 3 pregnancy losses, 9 urgent Caesarean sections, 2 emergency Caesarean sections, 1 fetal death, and 11 preterm births. Two patients presented a relapse during a median follow-up of 3.1 years (IQR 0.6-7.4). CONCLUSIONS: Strict medical surveillance of pregnant women with IE is required and must involve a multidisciplinary team including obstetricians and neonatologists. Furthermore, the potential risk of IE during pregnancy should never be underestimated in women with previously known underlying heart disease.

Shared risk factors for COVID-19 and preeclampsia in the first trimester: An observational study.

INTRODUCTION: The association between preeclampsia and coronavirus disease 2019 (COVID-19) is under study. Previous publications have hypothesized the existence of shared risk factors for both conditions or a deficient trophoblastic invasion as possible explanations for this association. The primary aim of this study was to examine baseline risk factors measured in the first-trimester combined screening for preeclampsia in pregnant women with COVID-19 compared with the general population. A secondary aim of this study was to compare risk factors among patients with mild and severe COVID-19. MATERIAL AND METHODS: This was an observational retrospective study conducted at Vall d'Hebron Hospital Campus (Catalonia, Spain). Study patients were 231 pregnant women undergoing the first-trimester screening for preeclampsia and positive for severe acute respiratory syndrome coronavirus 2 between February 2020 and September 2021. The reference cohort were 13 033 women of the general population from six centers across Catalonia from May 2019 to June 2021. Based on the need for hospitalization, patients were classified in two groups: mild and severe COVID-19. First-trimester screening for preeclampsia included maternal history, mean arterial blood pressure, mean uterine artery pulsatility index (UtAPI), placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A). RESULTS: The proportion of cases at high risk for preeclampsia was significantly higher among the COVID-19 group compared with the general population (19.0% and 13.2%, respectively; p = 0.012). When analyzing risk factors for preeclampsia individually, women with COVID-19 had higher median body mass index (25.2 vs 24.5, p = 0.041), higher UtAPI multiple of the median (MoM) (1.08 vs 1.00, p < 0.001), higher incidence of chronic hypertension (2.8% vs 0.9%, p = 0.015), and there were fewer smokers (5.7% vs 11.6%, p = 0.007). The MoMs of PlGF and PAPP-A did not differ significantly between both groups (0.96 vs 0.97, p = 0.760 and 1.00 vs 1.01, p = 0.432; respectively). CONCLUSIONS: In patients with COVID-19, there was a higher proportion of women at high risk for preeclampsia at the first-trimester screening than in the general population, mainly because of maternal risk factors, rather than placental signs of a deficient trophoblastic invasion.

Inherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance.

PURPOSE: Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown. METHODS: We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives. RESULTS: We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mycobacterial disease and were also heterozygous, resulting in 18 patients in total. Mycobacterial infection was the first clinical manifestation in 11 patients, at a mean age of 22.5 years (range: 12 to 42 years). Most patients also suffered from other infections, monocytopenia, or myelodysplasia. Strikingly, the clinical penetrance was incomplete (32.9% by age 40 years), as 16 heterozygous relatives aged between 6 and 78 years, including 4 older than 60 years, were completely asymptomatic. CONCLUSION: Clinical penetrance for mycobacterial disease was found to be similar to other GATA2 deficiency-related manifestations. These observations suggest that other mechanisms contribute to the phenotypic expression of GATA2 deficiency. A diagnosis of autosomal dominant GATA2 deficiency should be considered in patients with mycobacterial infections and/or other GATA2 deficiency-related phenotypes at any age in life. Moreover, all direct relatives should be genotyped at the GATA2 locus.

Secular trends in the epidemiology and clinical characteristics of Enterococcus faecalis infective endocarditis at a referral center (2007-2018).

The aim of the study was to analyze the epidemiological and clinical changes in EFIE. All definite IE episodes treated at a referral center between 2007 and 2018 were registered prospectively, and a trend test was used to study etiologies over time. EFIE cases were divided into three periods, and clinical differences between them were analyzed. All episodes of E. faecalis monomicrobial bacteremia (EFMB) between 2010 and 2018 and the percentage of echocardiograms performed were retrospectively collected. Six hundred forty-eight IE episodes were studied. We detected an increase in the percentage of EFIE (15% in 2007, 25.3% in 2018, P = 0.038), which became the most prevalent causative agent of IE during the last study period. One hundred and eight EFIE episodes were analyzed (2007-2010, n = 30; 2011-2014, n = 22; 2015-2018, n = 56). The patients in the last period were older (median 70.9 vs 66.5 vs 76.3 years, P = 0.015) and more frequently had an abdominal origin of EFIE (20% vs 13.6% vs 42.9%, P = 0.014), fewer indications for surgery (63.3% vs 54.6% vs 32.1%, P = 0.014), and non-significantly lower in-hospital mortality (30% vs 18.2% vs 12.5%, P = 0.139). There was an increase in the percentage of echocardiograms performed in patients with EFMB (30% in 2010, 51.2% in 2018, P = 0.014) and EFIE diagnoses (15% in 2010, 32.6% in 2018, P = 0.004). E. faecalis is an increasing cause of IE in our center, most likely due to an increase in the percentage of echocardiograms performed. The factors involved in clinical changes in EFIE should be thoroughly studied.

Gestation and COVID-19: clinical and microbiological observational study (Gesta-COVID19).

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. METHODS: Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. DISCUSSION: There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population.

Safety of tocilizumab in COVID-19 pregnant women and their newborn: A retrospective study.

WHAT IS KNOWN AND OBJECTIVE: Tocilizumab is an IL-6 receptor inhibitor agent which has been proposed as a candidate to stop the inflammatory phase of infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, safety data of tocilizumab in pregnant women and their newborn are scarce. We aimed to describe maternal and neonatal safety outcomes associated with tocilizumab treatment in pregnant women with severe COVID-19. METHODS: This is a retrospective study of severe COVID-19 pregnant women, treated with tocilizumab in two Spanish hospitals between 1 March and 31 April 2020. Demographics, medical history, clinical and radiologic findings, treatment information and laboratory data of mothers and their newborns were collected from electronic medical records. RESULTS AND DISCUSSION: A total of 12 pregnant women were identified to have received tocilizumab during pregnancy in the two hospitals. Median gestational age at admission was 27.7 weeks (interquartile range, 18.0-36.4). Most of them received lopinavir/ritonavir, azithromycin and hydroxychloroquine, two patients received corticosteroids and one received interferon beta 1B. All 12 pregnancies resulted in live births. Somatometric values were normal for all newborns, and evolution at 14 and 28 days was favourable for all of them. Hepatotoxicity was observed in 2 patients, which improved or resolved at discharge. Cytomegalovirus reactivation was detected in another patient who had also received corticosteroids for 15 days, causing a congenital infection in her newborn. Both hepatotoxicity and viral reactivation adverse events were classified as possibly related to tocilizumab administration according to Naranjo's causality algorithm. WHAT IS NEW AND CONCLUSIONS: It does not appear that tocilizumab has detrimental effects for the mother and newborn. Close monitoring of infections should be considered, especially if other immunosuppressive agents are used.

The association between vegetation size and surgical treatment on 6-month mortality in left-sided infective endocarditis.

AIMS: In left-sided infective endocarditis (IE), a large vegetation >10 mm is associated with higher mortality, yet it is unknown whether surgery during the acute phase opposed to medical therapy is associated with improved survival. We assessed the association between surgery and 6-month mortality as related to vegetation size. METHODS AND RESULTS: Patients with definite, left-sided IE (2008-2012) from The International Collaboration on Endocarditis prospective, multinational registry were included. We compared clinical characteristics and 6-month mortality (by Cox regression with inverse propensity of treatment weighting) between patients with vegetation size ≤10 mm vs. >10 mm in maximum length by surgical treatment strategy. A total of 1006 patients with left sided IE were included; 422 with a vegetation size ≤10 mm (median age 66.0 years, 33% women) and 584 (median age 58.4 years, 34% women) patients with a large vegetation >10 mm. Operative risk by STS-IE score was similar between groups. Embolic events occurred in 28.4% vs. 44.3% (P < 0.001), respectively. Patients with a vegetation >10 mm was associated with higher 6-month mortality (25.1% vs. 19.4% for small vegetation, P = 0.035). However, after propensity adjustment, the association with higher mortality persisted only in patients with a large vegetation >10 mm vs. ≤10 mm: hazard ratio (HR) 1.55 (1.27-1.90); but only in patients with large vegetation managed medically [HR 1.86 (1.48-2.34)] rather than surgically [HR 1.01 (0.69-1.49)]. CONCLUSION: Left-sided IE with vegetation size >10 mm was associated with an increased mortality at 6 months in this observational study but was dependent on treatment strategy. For patients with large vegetation undergoing surgical treatment, survival was similar to patients with smaller vegetation size.

Early Oral Switch to Linezolid for Low-risk Patients With Staphylococcus aureus Bloodstream Infections: A Propensity-matched Cohort Study.

BACKGROUND: Oral switch to linezolid is a promising alternative to standard parenteral therapy (SPT) in Staphylococcus aureus bacteremia (SAB). METHODS: We conducted a prospective cohort study of all adult cases of SAB between 2013 and 2017 in a Spanish university hospital. We compared the efficacy, safety, and length of hospital stay of patients receiving SPT and those where SPT was switched to oral linezolid between days 3 and 9 of treatment until completion. We excluded complicated SAB and osteoarticular infections. A k-nearest neighbor algorithm was used for propensity score matching with a 2:1 ratio. RESULTS: After propensity score matching, we included 45 patients from the linezolid group and 90 patients from the SPT group. Leading SAB sources were catheter related (49.6%), unknown origin (20.0%), and skin and soft tissue (17.0%). We observed no difference in 90-day relapse between the linezolid group and the SPT group (2.2% vs 4.4% respectively; P = .87). No statistically significant difference was observed in 30-day all-cause mortality between the linezolid group and the SPT group (2.2% vs 13.3%; P = .08). The median length of hospital stay after onset was 8 days in the linezolid group and 19 days in the SPT group (P < .01). No drug-related events leading to discontinuation were noted in the linezolid group. CONCLUSIONS: Treatment of SAB in selected low-risk patients with an oral switch to linezolid between days 3 and 9 of treatment until completion yielded similar clinical outcomes as SPT, allowing earlier discharge from the hospital.

Association between the timing of surgery for complicated, left-sided infective endocarditis and survival.

BACKGROUND: In patients with active infective endocarditis (IE), the relationship between timing of surgery and survival is uncertain. The objective was to evaluate clinical characteristics associated with timing of surgery and the association between surgical timing and 6-month survival in complicated, left-sided IE. METHODS: In a prospective, multicenter, observational registry (The International Collaboration on Endocarditis-PLUS, registry from 2008 to 2012), clinical factors associated with timing of surgery during the index hospitalization were determined among 485 adult patients with definite, complicated, left-sided IE who underwent cardiac surgery during their index hospitalization. The relationship between early surgical intervention (<7 days from admission to surgery center) and outcome after surgery was analyzed. The primary end point of the study was 6-month survival. RESULTS: The median time to surgery from admission to surgical center was 7 (interquartile range 2-15) days. Patients who underwent earlier surgery were more likely transferred to the surgical center (74.2% vs 46.4%, P < .001) and had a lower percentage of preexisting heart failure (before IE diagnosis) (6.0% vs 17.3%, P < .001) but higher rate of acute heart failure (53.2% vs 38.4%, P = .001). Variables independently associated with surgery <7 days from admission were patient transfer, acute heart failure, and nonelective surgical status (C-index = 0.84), but predicted operative risk was not. Cox proportional hazards modeling with inverse probability of treatment weighting found that earlier surgery was associated with a trend toward higher 6-month mortality compared with later surgery (hazard ratio = 1.68, 95% CI 0.97-2.96; P = .065), particularly surgery within 2 days of admission or transfer. Mortality was significantly associated with operative risk and complicated IE, including Staphylococcus aureus infection and presence of abscess. CONCLUSIONS: Earlier surgery in IE is strongly associated with acute heart failure and surgical urgency. After adjustment for operative risk and IE complications, earlier surgery <7 days from admission was associated with a trend toward higher 6-month overall mortality compared with surgery later in the index hospitalization.

Antimicrobial management of Tropheryma whipplei endocarditis: the Spanish Collaboration on Endocarditis (GAMES) experience.

OBJECTIVES: Tropheryma whipplei has been detected in 3.5% of the blood culture-negative cases of endocarditis in Spain. Experience in the management of T. whipplei endocarditis is limited. Here we report the long-term outcome of the treatment of previously reported patients who were diagnosed with infective endocarditis (IE) caused by T. whipplei from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) and discuss potential options for antimicrobial therapy for IE caused by T. whipplei. PATIENTS AND METHODS: Seventeen patients with T. whipplei endocarditis were recruited between 2008 and 2014 in 25 Spanish hospitals. Patients were classified according to the therapeutic regimen: ceftriaxone and trimethoprim/sulfamethoxazole, doxycycline + hydroxychloroquine and other treatment options. RESULTS: Follow-up data were obtained from 14 patients. The median follow-up was 46.5 months. All patients completed the antibiotic treatment prescribed, with a median duration of 13 months. Six patients were treated with ceftriaxone and trimethoprim/sulfamethoxazole (median duration 13 months), four with doxycycline + hydroxychloroquine (median duration 13.8 months) and four with other treatment options (median duration 22.3 months). The follow-up after the end of the treatments was between 5 and 84 months (median 24 months). CONCLUSIONS: All treatment lines were effective and well tolerated. Therapeutic failures were not detected during the treatment. None of the patients died or experienced a relapse during the follow-up. Only six patients received antibiotic treatment in accordance with guidelines. These data suggest that shorter antimicrobial treatments could be effective.

Correction to: Prognostic factors of mortality after surgery in infective endocarditis: systematic review and meta-analysis.

The original version of this article unfortunately contained a mistake.

Prognostic factors of mortality after surgery in infective endocarditis: systematic review and meta-analysis.

PURPOSE: There is a lack of consensus about which endocarditis-specific preoperative characteristics have an actual impact over postoperative mortality. Our objective was the identification and quantification of these factors. METHODS: We performed a systematic review of all the studies which reported factors related to in-hospital mortality after surgery for acute infective endocarditis, conducted according to PRISMA recommendations. A search string was constructed and applied on three different databases. Two investigators independently reviewed the retrieved references. Quality assessment was performed for identification of potential biases. All the variables that were included in at least two validated risk scores were meta-analyzed independently, and the pooled estimates were expressed as odds ratios (OR) with their confidence intervals (CI). RESULTS: The final sample consisted on 16 studies, comprising a total of 7484 patients. The overall pooled OR were statistically significant (p < 0.05) for: age (OR 1.03, 95% CI 1.00-1.05), female sex (OR 1.56, 95% CI 1.35-1.81), urgent or emergency surgery (OR 2.39 95% CI 1.91-3.00), previous cardiac surgery (OR 2.19, 95% CI 1.84-2.61), NYHA ≥ III (OR 1.84, 95% CI 1.33-2.55), cardiogenic shock (OR 4.15, 95% CI 3.06-5.64), prosthetic valve (OR 1.98, 95% CI 1.68-2.33), multivalvular affection (OR 1.35, 95% CI 1.01-1.82), renal failure (OR 2.57, 95% CI 2.15-3.06), paravalvular abscess (OR 2.39, 95% CI 1.77-3.22) and S. aureus infection (OR 2.27, 95% CI 1.89-2.73). CONCLUSIONS: After a systematic review, we identified 11 preoperative factors related to an increased postoperative mortality. The meta-analysis of each of these factors showed a significant association with an increased in-hospital mortality after surgery for active infective endocarditis. Graph summary of the Pooled Odds Ratios of the 11 preoperative factors analyzed after the systematic review and meta-analysis.