Risk Factors and Outcomes of Infections by Multidrug-Resistant Gram-Negative Bacteria in Patients Undergoing Hematopoietic Stem Cell Transplantation

Abstract The objective of this study was to determine risk factors and outcomes of infections by multidrug-resistant gram-negative (MDR GN) bacteria in 241 recipients of hematopoietic stem cell transplantation (HSCT). The cumulative incidence of infections was 10.5% (95% CI, 12.0% to 25.8%), with 57% of infections occurring during the period of severe neutropenia (neutrophil count  6 /L). In multivariate analysis, allogeneic transplant and colonization with MDR GN bacteria at admission to the transplant unit were significantly associated with an increased risk of infection. Although we observed neither transplant-related mortality (TRM) nor deaths due to infections by MDR GN bacteria after autologous transplant, in the allogeneic setting a significant difference was reported in terms of overall survival (OS) and TRM between patients who developed infections and those who did not (1-year OS, 39% versus 68%; 1-year TRM, 42% versus 19%). In multivariate analysis, refractory disease and development of grades III to IV graft-versus-host disease (GVHD) were factors that affected both TRM and OS, whereas occurrence of infections by MDR GN pathogens significantly reduced OS. We conclude that eligibility to allogeneic HSCT in MDR GN bacteria carriers should be carefully evaluated together with all other factors that independently influence outcome (disease status, donor, and GVHD risk)

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.Methods. A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.Results. C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P < .001) were associated with clinical success.Conclusions. Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT

Bacterial and fungal infections in kidney transplant recipients

Despite advances in the scientific knowledge related to organ transplantation, kidney transplant recipients remain patients who must take immunosuppressive therapy for the rest of their lives to prevent graft rejection. This situation, coupled with the possible need for medical care, whether invasive or noninvasive, and higher hospitalization rates than in the general population, puts the patient with a transplanted kidney at risk of developing infectious diseases. An important threat are bacterial infections of the urinary tract at different levels of severity (from asymptomatic bacteriuria to urinary septicemia), which in recent years have included infections by multidrug-resistant bacteria. Careful attention must be paid therefore to the overall management of kidney transplant recipients with infections and to the "ecological" use of antibiotic therapy, which aims at preventing antibiotic resistance according to the recent concept of antibiotic stewardship. Among the fungal infections candida infections require special consideration. As with bacterial infections, there may be different degrees of severity ranging from candiduria (where some see no indication for treatment) to pyelonephritis and candidemia, conditions that may lead to vascular complications and the possible rupture of blood vessels. The key to success in the fight against infections after kidney transplant lies in the multidisciplinary approach to their management, with the involvement of the nephrologist, transplant surgeon, infectiologist, clinical microbiologist and clinical pharmacologist

Linezolid underexposure in a patient co-treated with venlafaxine

none5sianoneCojutti P.; Crapis M.; Bassetti M.; Hope W.; Pea F.Cojutti P.; Crapis M.; Bassetti M.; Hope W.; Pea F

Treatment of consecutive episodes of multidrug-resistant bacterial pleurisy with different aetiology in a heart transplant candidate: Proof of concept of pharmacokinetic/pharmacodynamic optimisation of antimicrobial therapy at the infection site

reserved5nomixedPea F.; Cojutti P.; Merelli M.; Crapis M.; Bassetti M.Pea, F.; Cojutti, P.; Merelli, M.; Crapis, M.; Bassetti, M

Gentamicin once-daily in enterococcal endocarditis

Enterococcal endocarditis represents the third cause of infectious endocarditis (IE) following staphylococcal and streptococcal species and reaching up to 20% of all cases. Recently revised guidelines recommend the use of beta-lactams in association with gentamicin administered twice or three times daily for IE due to enterococcal strains that are documented to be susceptible to these compounds [2] and [3]. Enterococci are relatively impermeable to aminoglycosides. Cell wall-active agents (i.e., beta-lactams or glycopeptides) increase the permeability of the enterococcal membrane, and hence a bactericidal effect can be achieved by diffusion of the aminoglycoside at adequate concentrations without excessive toxicity. Thus, high concentration of aminoglycosides in the extracellular milieu during co-treatment with cell wall-active agents might allow increased drug level at the site of the ribosomal target within the bacterial cell for bactericidal activity. Accordingly, gentamicin once-daily administration should optimize Cmax/MIC ratio maximizing the efficacy and reducing the toxicity. Interestingly, favorable clinical outcome in the treatment of Enterococcus faecalis endocarditis using once-daily (OD) aminoglycoside regimen was previously and recently reported [4] and [5]. Our aim was therefore to report clinical and pharmacological data of patients with documented enterococcal IE treated with a single daily dose of gentamici

Prospectively validated dosing nomograms for maximizing the pharmacodynamics of vancomycin administered by continuous infusion in critically ill patients

The efficacy of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA)-related infections has been called into question by recent findings of higher rates of failure of vancomycin treatment of infections caused by strains with high MICs. Continuous infusion may be the best way to maximize the time-dependent activity of vancomycin. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL(Cr)) estimates for use in daily clinical practice to target the steady-state concentrations (C(ss)s) of vancomycin during continuous infusion at 15 to 20 mg/liter (after the administration of an initial loading dose of 15 mg/kg of body weight over 2 h). The correlation between vancomycin clearance (CL(v)) and CL(Cr) was retrospectively assessed in a cohort of critically ill patients (group 1, n = 70) to create a formula for dosage calculation to target C(ss) at 15 mg/liter. The performance of this formula was prospectively validated in a similar cohort (group 2, n = 63) by comparison of the observed and the predicted C(ss)s. A significant relationship between CL(v) and CL(Cr) was observed in group 1 (P < 0.001). The application of the calculated formula to vancomycin dosing in group 2 {infusion rate (g/24 h) = [0.029 x CL(Cr) (ml/min) + 0.94] x target C(ss) x (24/1,000)} led to a significant correlation between the observed and the predicted C(ss)s (r = 0.80, P < 0.001). Two dosing nomograms based on CL(Cr) were created to target the vancomycin C(ss) at 15 and 20 mg/liter in critically ill patients. These nomograms could be helpful in improving the vancomycin treatment of MRSA infections, especially in the presence of borderline-susceptible pathogens and/or of pathophysiological conditions which may enhance the clearance of vancomycin, while potentially avoiding the increased risk of nephrotoxicity observed with the use of high intermittent doses of vancomycin