Fidaxomicin monotherapy versus standard therapy combined with bezlotoxumab for treating patients with Clostridioides difficile infection at high risk of recurrence: a matched cohort study.

BACKGROUND: Both fidaxomicin and bezlotoxumab (used in combination with an antibiotic against Clostridioides difficile) achieve reductions in recurrence rates of C. difficile infection (CDI). However, the two strategies have never been compared. METHODS: Data from two retrospective cohorts of 'real-life' use of fidaxomicin and bezlotoxumab in combination with a standard anti-C. difficile antibiotic were used to compare the rates of recurrence of both strategies. Since the two cohorts were not identical, we used a propensity score analysis. RESULTS: Three hundred and two patients were included: 244 in the fidaxomicin cohort and 78 in the bezlotoxumab cohort. A history of renal failure or immunosuppression was more frequent in patients receiving bezlotoxumab (39.7% and 66.7% versus 26.6% and 38.9%; P = 0.03 and P < 0.001, respectively), but the severity and number of previous CDI episodes were similar in both cohorts. We observed that 19.3% of the patients in the fidaxomicin cohort experienced recurrence, compared with 14.1% in the bezlotoxumab cohort (OR 1.45; 95% CI 0.71-2.96; P = 0.29) but the difference remained non-significant after propensity score matching using previously defined variables (OR 1.24; 95% CI 0.50-3.07; P = 0.64). Moreover, the multivariate analysis did not show differences depending on the drug used. CONCLUSIONS: We observed that fidaxomicin and bezlotoxumab are prescribed in similar clinical scenarios, although those treated with bezlotoxumab have greater comorbidity. The proportion of recurrences was numerically lower in those treated with bezlotoxumab, although the propensity analysis did not find significant differences between the two drugs.

Role of mTOR inhibitors for the control of viral infection in solid organ transplant recipients.

Appropriate post-transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppressive drug with antiviral properties is not new, little effort has been made to put the evidence together to assess the management of immunosuppressive therapy in the presence of a viral infection. This review was developed to gather the evidence on antiviral activity of the mTORi against the viruses that most commonly reactivate in adult solid organ recipients: cytomegalovirus (CMV), polyomavirus, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and hepatitis C virus (HCV). A rapid review methodology and evaluation of quality and consistency of evidence based on the GRADE system was used. The existing literature was variable in nature, although indicating a potential advantage of mTORi in CMV, polyomavirus, and HHV8 infection, and a most doubtful relation with EBV and HCV infection. Several recommendations about the management of these infections are presented that can change certain current patterns of immunosuppression and help to improve the prognosis of the direct and indirect effects of viral infection in solid organ recipients.

[Daptomycin in Gram-positive bacterial infections in oncohematological patients and transplant recipients]. / Daptomicina en las infecciones por bacterias grampositivas en pacientes oncohematológicos y en receptores de trasplante.

Gram-positive infections are a major cause of morbidity and mortality in oncohematological patients and transplant recipients. The most frequently isolated Gram-positive organisms are the coagulase-negative staphylococci, Staphylococcus aureus and Enterococcus spp., and viridans group streptococci. Antibiotic resistance in these organisms is increasing and poses a challenge to clinicians. Daptomycin is rapidly bactericidal against a broad spectrum of gram-positive bacteria, including strains resistant to other drugs. The present article reviews some aspects of Gram-positive infections in these immunocompromised patients and provides a detailed analysis of experience with daptomycin in the treatment of these infections.

The impact of influenza A(H1N1)pdm09 infection on immunosuppressed patients.

Before the advent of the influenza A(H1N1)pdm virus in 2009, the information available about the clinical manifestations and prognosis of influenza in immunosuppressed patients was scarce. With the 2009 pandemic, knowledge of the behavior, severity and importance of antiviral therapy for influenza A infection in immunocompromised hosts has increased considerably. The aim of the present manuscript is to review the main challenges of influenza in the most representative immunosuppressed populations such as solid organ transplant recipients, hematopoietic stem cell transplant recipients, patients with solid and hematological cancer and human immunodeficiency virus infected patients.

GESITRA-SEIMC/REIPI recommendations for the management of cytomegalovirus infection in solid-organ transplant patients.

Cytomegalovirus infection remains a major complication of solid organ transplantation. In 2005 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, numerous publications have clarified or questioned the aspects covered in the previous document. These aspects include the situations and populations who must receive prophylaxis and its duration, the selection of the best diagnosis and monitoring technique and the best therapeutic strategy. For these reasons, we have developed new consensus guidelines to include the latest recommendations on post-transplant CMV management based on new evidence available.

Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study.

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.

Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection.

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

Brief communication: treatment of Enterococcus faecalis endocarditis with ampicillin plus ceftriaxone.

BACKGROUND: High-level aminoglycoside resistance (HLAR) that precludes bactericidal synergism with penicillins or glycopeptides and nephrotoxicity related to aminoglycoside treatment are major problems in treating Enterococcus faecalis endocarditis. OBJECTIVE: To evaluate the efficacy and safety of ampicillin plus ceftriaxone for treating endocarditis due to E. faecalis with and without HLAR. DESIGN: Observational, open-label, nonrandomized, multicenter clinical trial. SETTING: 13 centers in Spain. PATIENTS: 21 patients with HLAR E. faecalis endocarditis and 22 patients with non-HLAR E. faecalis endocarditis. All were at risk for nephrotoxicity related to aminoglycoside use. INTERVENTION: 6-week course of intravenous ampicillin, 2 g every 4 hours, plus intravenous ceftriaxone, 2 g every 12 hours. MEASUREMENTS: Clinical and microbiological outcomes. RESULTS: The clinical cure rate at 3 months was 67.4% (29 of 43 patients) among all episodes. During treatment, 28.6% of patients with HLAR E. faecalis endocarditis and 18.2% of patients with non-HLAR E. faecalis endocarditis died of infection-related causes. The rate of clinical and microbiological cure in patients who completed the protocol was 100% in the HLAR E. faecalis endocarditis group. No episodes of breakthrough bacteremia occurred, although there were 2 relapses in the non-HLAR E. faecalis endocarditis group. Treatment was withdrawn in 1 case because of fever and skin rash. LIMITATIONS: The study had a small sample and was observational. CONCLUSION: The combination of ampicillin and ceftriaxone is effective and safe for treating HLAR E. faecalis endocarditis and could be a reasonable alternative for patients with non-HLAR E. faecalis endocarditis who are at increased risk for nephrotoxicity.

Tuberculosis in immunosuppressed patients. / Tuberculosis en pacientes inmunodeprimidos.

Tuberculosis (TB) is one of the most significant infections in immunosuppressed patients due to its high frequency and high morbidity and mortality. TB is the leading cause of death among HIV-infected patients. The diagnosis and early treatment of latent tuberculosis infection is vital to preventing it progression to disease. Similarly, the early diagnosis of TB is key to improving the prognosis of patients and preventing its transmission. The clinical expression of TB in immunosuppressed patients is conditioned by the patient's degree of immunosuppression. It is important to keep this peculiarity in mind so as not to delay the diagnosis of suspected TB. TB treatment is basically the same in immunosuppressed patients as in the general population and any differences mainly derive from pharmacological interactions. We examined the diagnosis and treatment of TB and latent tuberculosis infection in immunosuppressed patients.

[Variability in coronary risk assessment in HIV-infected patients]. / Variabilidad en la valoración del riesgo coronario en pacientes infectados por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: Antiretroviral treatment of human immunodeficiency virus (HIV)-infected patients seems to increase the coronary risk (CR) in these patients. Adequate assessment of CR has significant implications for the management of these patients. Our objective was to compare 2 systems for assessing 10-year CR in HIV-infected patients. PATIENTS AND METHOD: CR was calculated in a prospective cohort of 205 HIV-infected patients using Framingham tables and REGICOR adapted tables. Prevalence of cardiovascular risk factors in these patients was evaluated. RESULTS: Mean age (standard deviation) was 41.4 (8.2) years. Most patients were taking antiretrovirals and had a good immunological status. Current smoking was reported by 77.1% of patients, while a history of dyslipidemia, hypertension, or diabetes was found in 29.3%, 7.3%, and 4.9% of patients, respectively. Lipodystrophy was seen in 41% of patients, abdominal obesity in 21.5%, and a sedentary lifestyle in 50.7% Mean values obtained were 6.55 (6.36) in the Framingham scale and 2.85 (2.31) in the REGICOR scale. A 10-year CR greater than 10% was found in 26 patients (12.9%) with the Framingham tables and in 4 patients (2.0%) with the REGICOR tables. The difference between both methods was significant (p < 0.001). CONCLUSIONS: Application of the Framingham tables to our cohort may overestimate the CR. Studies aimed at identifying the most adequate method for measuring CR in HIV-infected patients are required. Until such data are available, estimation of CR in these patients should be taken with caution.

Voriconazole treatment for less-common, emerging, or refractory fungal infections.

Treatments for invasive fungal infections remain unsatisfactory. We evaluated the efficacy, tolerability, and safety of voriconazole as salvage treatment for 273 patients with refractory and intolerant-to-treatment fungal infections and as primary treatment for 28 patients with infections for which there is no approved therapy. Voriconazole was associated with satisfactory global responses in 50% of the overall cohort; specifically, successful outcomes were observed in 47% of patients whose infections failed to respond to previous antifungal therapy and in 68% of patients whose infections have no approved antifungal therapy. In this population at high risk for treatment failure, the efficacy rates for voriconazole were 43.7% for aspergillosis, 57.5% for candidiasis, 38.9% for cryptococcosis, 45.5% for fusariosis, and 30% for scedosporiosis. Voriconazole was well tolerated, and treatment-related discontinuations of therapy or dose reductions occurred for <10% of patients. Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections.

Universal prophylaxis with fluconazole for the prevention of early invasive fungal infection in low-risk liver transplant recipients.

BACKGROUND: Although antifungal prophylaxis in high-risk liver transplant recipients (LTR) seems to be clearly justified, the efficacy of universal prophylaxis (UP) including low-risk patients is controversial. METHODS: From the study cohort RESITRA-REIPI, which prospectively analyzed 1010 LTR (September 2003 to February 2005) in 12 Spanish hospitals, we compared the incidence of early invasive fungal infection (IFI, first 90 days) between centers performing or not UP with fluconazole (for a minimum of 7 days) in low-risk LTR (none of the following: posttransplant renal failure, urgent transplant/retransplant, or choledochojejunostomy). RESULTS: Three of 12 centers used UP. A total of 799 LTR were considered as low-risk patients (206 included in the UP group and 593 did not). We reported a total of 11 episodes of early IFI (six due to Candida albicans, one due to C. guillermondii, and three due to Aspergillus fumigatus) in 10 patients (incidence: 1.2%), with two cases of death attributable to IFI (18%) in both patients with invasive aspergillosis. There were no differences in the incidence of IFI between the patients receiving or not UP (4/206:1.9% vs. 6/593:1%, respectively; P=0.36). CONCLUSIONS: IFI is infrequent in LTR not fulfilling major high-risk factors criteria, and prophylaxis with fluconazole in this low-risk group does not seem to be justified.

[Teaching of infectious diseases in medical degree studies]. / La docencia de la patología infecciosa en los estudios de grado de medicina.

The teaching of the infectious diseases in the Bachelor of Medicine degree consists of activities aimed at providing the student with levels of competence in this area (knowledge, abilities, attitudes) appropriate for a general physician, and to give them a solid base to achieve the skills and abilities for becoming a specialist in this area. Currently, the location, the amount and quality of infectious diseases studies in the Bachelor of Medicine degree are very disparate between the different Spanish Medical Schools. The incorporation into the European Higher Education Area, with the necessary adaptation of curricula, will enable the contents and the teaching objectives in this field to be better defined. The latest document from the Medical Schools Deans Conference clearly identifies the studies of the infectious diseases into the Medical Diseases module and in the area of human clinical training. In our opinion, infectious diseases must be considered as a major subject, preferably in the second semester of the fifth year, and having a minimum of 6 and a maximum of 9 ECTS, theoretical and practical, distributed equally among attendance, part-attendance and self-teaching credits. Infectious diseases pathology must be horizontally integrated with most of the other subjects in the clinical module and vertically integrated with the subject of microbiology. The coordination and most of the teaching of the credits in the infectious diseases subject must be done by specialists with clinical activity in infectious diseases.

[Infectious disease assessment in solid organ transplant candidates]. / Evaluación de las enfermedades infecciosas en el candidato a un trasplante de órgano sólido.

BACKGROUND: Infections are one of the leading causes of morbidity and mortality in solid organ transplant recipients. Many of these infections can be prevented or their effects reduced by accurate preoperative evaluation of risk in the transplantation candidate. The elaboration of guidelines using a multidisciplinary approach can help to establish more rational diagnostic, therapeutic, and preventive measures in this setting. OBJECTIVE: To elaborate guidelines for the assessment of infectious diseases in transplant candidates, based on consensus among professionals in this field and under the auspices of Spanish scientific societies. MATERIAL AND METHODS: The Infections in Transplant Patients Group (GESITRA), within the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), appointed a panel of four microbiologists and infectious disease specialists to elaborate a draft of the guidelines, which was subsequently approved by all the members of this Group. With the support of the National Transplant Organization, the GESITRA document was then presented to various professionals in this field so they could provide their comments and suggestions. RESULTS: The final document, after incorporation of all appropriate modifications and suggestions, is presented herein. The guidelines focus on the following: a) diagnosis of active and latent infections, and identification of risk factors in the candidate; b) recommended approach for infections diagnosed during the evaluation process and their corresponding treatment; c) definition of infections contraindicating transplantation; and d) prevention of post-transplantation infectious complications by systematic vaccination and instruction on preventive measures provided to patients, their relatives, and persons living with them. DISCUSSION: Using a multidisciplinary approach that included the efforts of experts in the field and the collaboration of scientific societies, a comprehensive document containing specific recommendations was elaborated. Systematic review of the guidelines in the future is considered worthwhile by both the authors and supporters of this document.