Infective Endocarditis After Transcatheter Versus Surgical Aortic Valve Replacement.

BACKGROUND: Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR versus TAVR. METHODS: Data were collected from the "Infectious Endocarditis after TAVR International" (enrollment from 2005 to 2020) and the "International Collaboration on Endocarditis" (enrollment from 2000 to 2012) registries. Only patients with an IE affecting the aortic valve prosthesis were included. A 1:1 paired matching approach was used to compare patients with TAVR and SAVR. RESULTS: A total of 1688 patients were included. Of them, 602 (35.7%) had a surgical bioprosthesis (SB), 666 (39.5%) a mechanical prosthesis, 70 (4.2%) a homograft, and 350 (20.7%) a transcatheter heart valve. In the SAVR versus TAVR matched population, the rate of new moderate or severe aortic regurgitation was higher in the SB group (43.4% vs 13.5%; P < .001), and fewer vegetations were diagnosed in the SB group (62.5% vs 82%; P < .001). Patients with an SB had a higher rate of perivalvular extension (47.9% vs 27%; P < .001) and Staphylococcus aureus was less common in this group (13.4% vs 22%; P = .033). Despite a higher rate of surgery in patients with SB (44.4% vs 27.3%; P < .001), 1-year mortality was similar (SB: 46.5%; TAVR: 44.8%; log-rank P = .697). CONCLUSIONS: Clinical presentation, type of causative microorganism, and treatment differed between patients with an IE located on SB compared with TAVR. Despite these differences, both groups exhibited high and similar mortality at 1-year follow-up.

Infective endocarditis caused by penicillin-resistant viridans group streptococci: a series of nine cases from a Spanish cohort.

BACKGROUND: Infective endocarditis (IE) caused by viridans and gallolyticus group streptococci (VGS-GGS) resistant to penicillin (PEN-R; minimum inhibitory concentration ≥4 mg/L) is rare but poses therapeutic challenges. OBJECTIVES: To describe the characteristics of patients with IE caused by PEN-R VGS-GGS, focusing on antimicrobial management. METHODS: Retrospective analysis of a prospective cohort of definite IE caused by PEN-R VGS-GGS between 2008 and 2023 in 40 Spanish hospitals. We describe clinical characteristics, management and outcome of the cases, and compare them to IE caused by VGS-GGS with susceptibility or susceptibility with increased exposure to penicillin (PEN-I). RESULTS: We identified nine cases of PEN-R VGS-GGS IE in a cohort of 1563 streptococcal IE (0.58%). All isolates belonged to S. mitis group. Three cases died during hospitalization and no relapse occurred at 3 months of follow-up. Compared to cases with susceptibility or PEN-I, PEN-R showed a higher rate of mitral location (78% versus 51%), surgical indication (67% versus 51%), and in-hospital mortality (33% versus 12%). Most cases (86%) showed resistance to third-generation cephalosporins. The preferred antibiotic regimen was beta-lactam-based: ceftriaxone plus gentamicin, penicillin plus gentamicin, ceftriaxone plus levofloxacin, and ceftaroline plus daptomycin. Two cases received a combination of vancomycin plus gentamicin. Levofloxacin was used in two cases in combination with ceftriaxone or daptomycin. All patients that received cardiac surgery were cured at the end of follow-up. CONCLUSIONS: IE caused by PEN-R VGS-GGS was rare and only affected mitis group streptococci. Antibiotic combination including a beta-lactam seems to be effective in its management.

Effect of a bundle intervention on adherence to quality-of-care indicators and on clinical outcomes in patients with Staphylococcus aureus bacteraemia hospitalized in non-referral community hospitals.

BACKGROUND: Although a significant number of cases of Staphylococcus aureus bacteraemia (SAB) are managed at non-referral community hospitals, the impact of a bundle-of-care intervention in this setting has not yet been explored. METHODS: We performed a quasi-experimental before-after study with the implementation of a bundle of care for the management of SAB at five non-referral community hospitals and a tertiary care university hospital. Structured recommendations for the five indicators selected to assess quality of care were provided to investigators before the implementation of the bundle and monthly thereafter. Primary endpoints were adherence to the bundle intervention and treatment failure, defined as death or relapse at 90 days of follow-up. RESULTS: One hundred and seventy patients were included in the pre-intervention period and 103 in the intervention period. Patient characteristics were similar in both periods. Multivariate analysis controlling for potential confounders showed that performance of echocardiography was the only factor associated with improved adherence to the bundle in the intervention period (adjusted OR 2.13; 95% CI 1.13-4.02). Adherence to the bundle, performance of follow-up blood cultures, and adequate duration of antibiotic therapy for complicated SAB presented non-significant improvements. The intervention was not associated with a lower rate of 90 day treatment failure (OR 1.11; 95% CI 0.70-1.77). CONCLUSIONS: A bundle-of-care intervention for the management of SAB at non-referral community hospitals increased adherence to quality indicators, but did not significantly reduce rates of 90 day mortality or relapse.

Clinical characteristics and outcomes of aortic prosthetic valve endocarditis: comparison between transcatheter and surgical bioprostheses.

PURPOSE: Most data regarding infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) comes from TAVI registries, rather than IE dedicated cohorts. The objective of our study was to compare the clinical and microbiological profile, imaging features and outcomes of patients with IE after SAVR with a biological prosthetic valve (IE-SAVR) and IE after TAVI (IE-TAVI) from 6 centres with an Endocarditis Team (ET) and broad experience in IE. METHODS: Retrospective analysis of prospectively collected data. From the time of first TAVI implantation in each centre to March 2021, all consecutive patients admitted for IE-SAVR or IE-TAVI were prospectively enrolled. Follow-up was monitored during admission and at 12 months after discharge. RESULTS: 169 patients with IE-SAVR and 41 with IE-TAVI were analysed. Early episodes were more frequent among IE-TAVI. Clinical course during hospitalization was similar in both groups, except for a higher incidence of atrioventricular block in IE-SAVR. The most frequently causative microorganisms were S. epidermidis, Enterococcus spp. and S. aureus in both groups. Periannular complications were more frequent in IE-SAVR. Cardiac surgery was performed in 53.6% of IE-SAVR and 7.3% of IE-TAVI (p=0.001), despite up to 54.8% of IE-TAVI patients had an indication. No differences were observed about death during hospitalization (32.7% vs 35.0%), and at 1-year follow-up (41.8% vs 37.5%), regardless of whether the patient underwent surgery or not. CONCLUSION: Patients with IE-TAVI had a higher incidence of early prosthetic valve IE. Compared to IE-SAVR, IE-TAVI patients underwent cardiac surgery much less frequently, despite having surgical indications. However, in-hospital and 1-year mortality rate was similar between both groups.

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.

Cytokine response as a biomarker for early diagnosis and outcome prediction of stem cell transplant recipients and acute leukemia patients with invasive aspergillosis.

We aimed to determine the role of serum cytokine expression in invasive aspergillosis (IA) diagnosis and outcome prediction in hematologic patients. In this multicenter study, serum cytokines (IL6, IL10, INF-gamma, IL12, IL4, TNF-alpha, IL17, and IL23) were prospectively recruited from all consecutive patients with hematologic malignances at IA diagnosis and compared to control patients matched by center, age, baseline disease, and therapeutic regimen. We included 36 patients with IA and 36 controls. Serum levels of IL6 and IL10 cytokines on day 0 were significantly increased in patients with IA when compared to controls (P = 0.001 and P = 0.025, respectively), even in those who were neutropenic. No differences were observed for the other cytokines. IL6 and IL10 predicted IA with an area under the ROC curve of 0.74 (95% CI 0.62-0.86) and 0.64 (95% CI 0.51-0.77), respectively. The best cutoff point in predicting IA was 20.85 pg/ml for IL6 (sensitivity 72.2%; specificity 77.8%; PPV 76.5% and NPV 73.7%), and 0.045 pg/ml for IL10 (sensitivity 62.9%; specificity 63.9%; PPV 62.9% and NPV 63.9%). IL6 levels were associated with increased mortality, with the best cutoff value being 65.59 pg/ml in mortality prediction. In conclusion, in addition to current tests in place, IL6 and IL10 levels-as measured in plasma-may help clinicians diagnose IA. High levels of IL6 at IA diagnosis are related with worse outcomes. LAY SUMMARY: We evaluated the role of serum cytokine expression in invasive aspergillosis (IA) diagnosis and outcome. Serum levels of IL6 and IL10 are increased in patients with IA compared to controls, and IL6 levels are associated with mortality.

Infective Endocarditis: New Challenges in a Classic Disease.

Infective endocarditis is a relatively rare, but deadly infection, with an overall mortality of around 20% in most series. Clinical manifestations have evolved in response to significant epidemiological shifts in industrialized nations, with a move toward a nosocomial or health-care-related pattern, in older patients, with more episodes associated with prostheses and/or intravascular electronic devices and a predominance of staphylococcal and enterococcal etiology.Diagnosis is often challenging and is based on the conjunction of clinical, microbiological, and imaging information, with notable progress in recent years in the accuracy of echocardiographic data, coupled with the recent emergence of other useful imaging techniques such as cardiac computed tomography (CT) and nuclear medicine tools, particularly 18F-fluorodeoxyglucose positron emission/CT.The choice of an appropriate treatment for each specific case is complex, both in terms of the selection of the appropriate agent and doses and durations of therapy as well as the possibility of using combined bactericidal antibiotic regimens in the initial phase and finalizing treatment at home in patients with good evolution with outpatient oral or parenteral antimicrobial therapies programs. A relevant proportion of patients will also require valve surgery during the active phase of treatment, the timing of which is extremely difficult to define. For all the above, the management of infective endocarditis requires a close collaboration of multidisciplinary endocarditis teams.

Ceftolozane/tazobactam for difficult-to-treat Gram-negative infections: A real-world tertiary hospital experience.

OBJECTIVE: To evaluate the real-world clinical efficacy of ceftolozane/tazobactam (C/T) in difficult-to-treat infections caused by multi-drug resistant Gram-negative microorganisms, including carbapenem-resistant Pseudomonas aeruginosa. METHODS: Retrospective cohort study of adult patients treated with C/T for at least 48 hours for infections caused by multi-drug resistant Gram-negative bacteria in a tertiary hospital from May 2016 until August 2019. The primary outcome analysed was clinical failure, defined as a composite of symptomatology persistence after 7 days of C/T treatment, infection recurrence, and/or all-cause mortality within 30 days of follow-up. RESULTS AND DISCUSSION: 96 episodes of C/T treatment were included, mostly consisting of targeted treatments (83.9%) for the following sources of infection: intra-abdominal (22.6%), urinary tract (25.8%), skin and soft tissue (19.4%), hospital-acquired pneumonia (14%), and other (6.4%). The most frequently isolated bacteria were carbapenem-resistant (88, 94.6%). Clinical failure rate was 30.1%, due to persistent infection at day 7 (4.3%), recurrence of the initial infection (16.1%), or 30-day all-cause mortality (8.6%). Adverse events most frequently reported were Clostridium difficile infection (9%) and cholestasis (8%). WHAT IS NEW AND CONCLUSION: C/T showed a favourable clinical profile for difficult-to-treat multidrug-resistant and carbapenem-resistant Gram-negative infections, regardless of the source of infection.

A Care Bundle Intervention to Prevent Surgical Site Infections After a Craniotomy.

BACKGROUND: Although surgical site infections after a craniotomy (SSI-CRANs) are a serious problem that involves significant morbidity and costs, information on their prevention is scarce. We aimed to determine whether the implementation of a care bundle was effective in preventing SSI-CRANs. METHODS: A historical control study was used to evaluate the care bundle, which included a preoperative shower with 4% chlorhexidine soap, appropriate hair removal, adequate preoperative systemic antibiotic prophylaxis, the administration of 1 g of vancomycin powder into the subgaleal space before closing, and a postoperative dressing of the incisional surgical wound with a sterile absorbent cover. Patients were divided into 2 groups: preintervention (January 2013 to December 2015) and intervention (January 2016 to December 2017). The primary study end point was the incidence of SSI-CRANs within 1 year postsurgery. Propensity score matching was performed, and differences between the 2 study periods were assessed using Cox regression models. RESULTS: A total of 595 and 422 patients were included in the preintervention and intervention periods, respectively. The incidence of SSI-CRANs was lower in the intervention period (15.3% vs 3.5%; P < .001). Using a propensity score model, 421 pairs of patients were matched. The care bundle intervention was independently associated with a reduced incidence of SSI-CRANs (adjusted odds ratio, 0.23; 95% confidence interval, .13-.40; P < .001). CONCLUSIONS: The care bundle intervention was effective in reducing SSI-CRAN rates. The implementation of this multimodal preventive strategy should be considered in centers with high SSI-CRAN incidences.

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial.

BACKGROUND: We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. METHODS: A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. RESULTS: Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). CONCLUSIONS: Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. CLINICAL TRIALS REGISTRATION: NCT01898338.

An evidence-based bundle improves the quality of care and outcomes of patients with candidaemia.

BACKGROUND: Candidaemia is a leading cause of bloodstream infections in hospitalized patients all over the world. It remains associated with high mortality. OBJECTIVES: To assess the impact of implementing an evidence-based package of measures (bundle) on the quality of care and outcomes of candidaemia. METHODS: A systematic review of the literature was performed to identify measures related to better outcomes in candidaemia. Eight quality-of-care indicators (QCIs) were identified and a set of written recommendations (early treatment, echinocandins in septic shock, source control, follow-up blood culture, ophthalmoscopy, echocardiography, de-escalation, length of treatment) was prospectively implemented. The study was performed in 11 tertiary hospitals in Spain. A quasi-experimental design before and during bundle implementation (September 2016 to February 2018) was used. For the pre-intervention period, data from the prospective national surveillance were used (May 2010 to April 2011). RESULTS: A total of 385 and 263 episodes were included in the pre-intervention and intervention groups, respectively. Adherence to all QCIs improved in the intervention group. The intervention group had a decrease in early (OR 0.46; 95% CI 0.23-0.89; P = 0.022) and overall (OR 0.61; 95% CI 0.4-0.94; P = 0.023) mortality after controlling for potential confounders. CONCLUSIONS: Implementing a structured, evidence-based intervention bundle significantly improved patient care and early and overall mortality in patients with candidaemia. Institutions should embrace this objective strategy and use the bundle as a means to measure high-quality medical care of patients.

Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts.

BACKGROUND: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. METHODS: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). RESULTS: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). CONCLUSIONS: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.

Impact of ß-Lactam and Daptomycin Combination Therapy on Clinical Outcomes in Methicillin-susceptible Staphylococcus aureus Bacteremia: A Propensity Score-matched Analysis.

BACKGROUND: Mortality rates from Staphylococcus aureus bacteremia are high and have only modestly improved in recent decades. We compared the efficacies of a ß-lactam in combination with daptomycin (BL/D-C) and ß-lactam monotherapy (BL-M) in improving clinical outcomes in methicillin-susceptible S. aureus (MSSA) bacteremia. METHODS: A retrospective cohort study of MSSA bacteremia was performed in a tertiary hospital from January 2011 to December 2017. Patients receiving BL/D-C and BL-M were compared to assess 7-, 30-, and 90-day mortality rates. A 1:2 propensity score matching analysis was performed. Differences were assessed using Cox regression models. RESULTS: Of the 514 patients with MSSA bacteremia, 164 were excluded as they had received combination therapies other than BL/D-C, had pneumonia, or died within 48 hours of admission. Of the remaining 350 patients, 136 and 214 received BL/D-C and BL-M, respectively. BL/D-C patients had higher Pitt scores and persistent bacteremia more often than BL-M patients. In the raw analysis, there were no differences in mortality rates between groups. After propensity score matching, there were no significant differences between the BL/D-C (110 patients) and BL-M (168 patients) groups for all-cause mortality rates at 7 days (8.18% vs 7.74%; P = 1.000), 30 days (17.3% vs 16.1%; P = .922), and 90 days (22.7% vs 23.2%; P = 1.000), even in a subanalysis of patients with high-risk source of infection and in a subgroup excluding catheter-related bacteremia. CONCLUSIONS: BL/D-C failed to reduce mortality rates in patients with MSSA bacteremia. Treatment strategies to improve survival in MSSA bacteremia are urgently needed.

Optimizing therapy of bloodstream infection due to extended-spectrum ß-lactamase-producing Enterobacteriaceae.

PURPOSE OF REVIEW: Infections due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) are increasing worldwide. Carbapenems are usually regarded as the antibiotics of choice for the treatment of serious ESBL infections. However, because of the alarming emergence or carbapenem resistance, interest in effective alternatives has emerged. The present review summarizes the findings published on the antibiotics currently available for treatment of patients with an ESBL-E bloodstream infection (BSI). RECENT FINDINGS: Meropenem and imipenem are the drugs recommended for treatment of ESBL BSIs in critically ill patients, and in infections with high bacterial loads or elevated ß-lactam minimum inhibitory concentrations. Ertapenem should be reserved for patients with less severe presentations, and should be used at high doses. In milder presentations or BSIs from low-risk sources, other carbapenem-sparing alternatives could be considered: cephamycins, fluoroquinolones, and particularly a ß-lactam/ß-lactam inhibitor combination (particularly piperacillin/tazobactam). Optimized dosing of piperacillin/tazobactam is recommended (high doses and extended infusion). There are few data on the use of the promising newly available drugs (e.g. ceftolozane/tazobactam, ceftazidime/avibactam, cefiderocol, and plazomicin), and it seems reasonable to reserve them as last-resort drugs. SUMMARY: Carbapenems should be used in patients with serious infections; alternatives could be used individually, particularly for definitive treatment of patients with milder presentations.

Usefulness of guideline recommendations for prognosis in patients with candidemia.

We aimed to analyze whether the lack of inclusion of specific recommendations for the management of candidemia is an independent risk factor for early and overall mortality. Multicenter study of adult patients with candidemia in 13 hospitals. We assessed the proportion of patients on whom nine specific ESCMID and IDSA guidelines recommendations had been applied, and analyzed its impact on mortality. 455 episodes of candidemia were documented. Patients who died within the first 48 hours were excluded. Sixty-two percent of patients received an appropriate antifungal treatment. Either echinocandin or amphotericin B therapy were administered in 43% of patients presenting septic shock and in 71% of those with neutropenia. Sixty-one percent of patients with breakthrough candidemia underwent a change in antifungal drug class. Venous catheters were removed in 79% of cases. Follow-up blood cultures were performed in 72% of cases. Ophthalmoscopy and echocardiogram were performed in 48% and 50% of patients, respectively. Length of treatment was appropriate in 78% of cases. Early (2-7 days) and overall (2-30 days) mortality were 8% and 27.7%, respectively. Inclusion of less than 50% of the specific recommendations was independently associated with a higher early (HR = 7.02, 95% CI: 2.97-16.57; P < .001) and overall mortality (HR = 3.55, 95% CI: 2.24-5.64; P < .001). In conclusion, ESCMID and IDSA guideline recommendations were not performed on a significant number of patients. Lack of inclusion of these recommendations proved to be an independent risk factor for early and overall mortality.

Candidemia in solid organ transplant recipients in Spain: Epidemiological trends and determinants of outcome.

BACKGROUND: Despite being considered a high-risk population for invasive fungal disease, specific features of candidemia among solid organ transplant (SOT) recipients remain poorly characterized. METHODS: We compiled prospective data from two multicenter studies on candidemia performed over two consecutive periods in Spain: the CANDIPOP Study (2010-2011) and the CANDI-Bundle Study (2016-2018). Episodes diagnosed in adult SOT recipients in 10 participating centers were included. Risk factors for clinical failure (all-cause 7-day mortality and/or persistent candidemia for ≥72 hours) and 30-day mortality were investigated by univariate analysis. RESULTS: We included 55 episodes of post-transplant candidemia (32 and 23 of which occurred during the first and second periods). Kidney (38.2%) and liver recipients (30.9%) were the most common populations. Candida albicans accounted for 27.3% of episodes. The proportion of C glabrata increased over time (18.8% vs 30.4% for the first and second periods). There were no differences in the rate of fluconazole non-susceptible isolates (50.0% vs 60.0%, respectively). Clinical failure and 30-day mortality occurred in 25.5% and 27.3% of episodes and were associated with the severity of candidemia (Pitt score and severe sepsis/septic shock). Kidney transplantation (unadjusted odds ratio [uOR]: 0.17; 95% confidence interval [CI]: 0.03-0.85; P-value = .020), early catheter removal (uOR: 0.15; 95% CI: 0.03-0.76; P-value = .013), and appropriate early antifungal therapy (uOR: 0.14; 95% CI: 0.02-0.89; P-value = .041) were protective for 30-day mortality. CONCLUSIONS: High rates of non-albicans species and fluconazole non-susceptibility must be taken into account to optimize therapeutic management and outcomes in SOT recipients with candidemia.

Echinocandins Compared to Fluconazole for Candidemia of a Urinary Tract Source: A Propensity Score Analysis.

BACKGROUND: Whether echinocandins could be used to treat candidemia of a urinary tract source (CUTS) is unknown. We aimed to provide current epidemiological information of CUTS and to compare echinocandin to fluconazole treatment on CUTS outcomes. METHODS: A multicenter study of adult patients with candidemia was conducted in 9 hospitals. CUTS was defined as a candidemia with concomitant candiduria by the same organism associated with significant urological comorbidity. The primary outcome assessed was clinical failure (defined by 7-day mortality or persistent candidemia) in patients treated with either an echinocandin or fluconazole. A propensity score was calculated and then entered into a regression model. RESULTS: Of 2176 episodes of candidemia, 128 were CUTS (5.88%). Most CUTS cases were caused by Candida albicans (52.7%), followed by Candida glabrata (25.6%) and Candida tropicalis (16.3%). Clinical failure occurred in 7 patients (20%) treated with an echinocandin and in 15 (17.1%) treated with fluconazole (P = .730). Acute renal failure (adjusted odds ratio [AOR], 3.01; 95% confidence interval [CI], 1.01-8.91; P = .047) was the only independent factor associated with clinical failure, whereas early urinary tract drainage procedures (surgical, percutaneous, or endoscopic) were identified as protective (AOR, 0.08; 95% CI, .02-.31; P < .001). Neither univariate nor multivariate analysis showed that echinocandin therapy altered the risk of clinical failure. CONCLUSIONS: Initial echinocandin therapy was not associated with clinical failure in patients with CUTS. Notably, acute renal failure predicted worse outcomes and performing an early urologic procedure was a protective measure.

Carbapenem-resistant and carbapenem-susceptible isogenic isolates of Klebsiella pneumoniae ST101 causing infection in a tertiary hospital.

BACKGROUND: In this study we describe the clinical and molecular characteristics of an outbreak due to carbapenem-resistant Klebsiella pneumoniae (CR-KP) producing CTX-M-15 and OXA-48 carbapenemase. Isogenic strains, carbapenem-susceptible K. pneumoniae (CS-KP) producing CTX-M-15, were also involved in the outbreak. RESULTS: From October 2010 to December 2012 a total of 62 CR-KP and 23 CS-KP were isolated from clinical samples of 42 patients (22 had resistant isolates, 14 had susceptible isolates, and 6 had both CR and CS isolates). All patients had underlying diseases and 17 of them (14 patients with CR-KP and 3 with CS-KP) had received carbapenems previously. The range of carbapenem MICs for total isolates were: imipenem: 2 to >32 µg/ml vs. <2 µg/ml; meropenem: 4 to >32 µg/ml vs. <2 µg/ml; and ertapenem: 8 to >32 µg/ml vs. <2 µg/ml. All the isolates were also resistant to gentamicin, ciprofloxacin, and cotrimoxazole. Both types of isolates shared a common PFGE pattern associated with the multilocus sequence type 101 (ST101). The bla CTX-M-15 gene was detected in all the isolates, whereas the bla OXA-48 gene was only detected in CR-KP isolates on a 70 kb plasmid. CONCLUSIONS: The clonal spread of K. pneumoniae ST101 expressing the OXA-48 and CTX-M-15 beta-lactamases was the cause of an outbreak of CR-KP infections. CTX-M-15-producing isolates lacking the bla OXA-48 gene coexisted during the outbreak.