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

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Prosthetic joint infections

reserved4noPurpose of reviewProsthetic joint infections (PJIs) represent one of the most disastrous complications in prosthetic surgery, requiring long hospitalization, prolonged antimicrobial treatment and repeated surgical interventions. No gold standard test to formulate diagnosis exist. A combination of high index of suspicion, physical examination, microbiological and biohumoral investigations is required. Therapeutical approach should be based on a multidisciplinary team. In our center, a two-stage approach is preferred. As regards the choice of the empirical antibiotic backbone, individual risk factors for multiple-drug resistant (MDR) pathogens should be considered. Several studies enhance the possibility to shorten the length of antibiotic couses.Recent findingsSome interesting improvements have been made in the setting of PJIs management. As regards diagnosis, novel biomarkers and nuclear imaging are acquiring more importance. Molecular biology techniques also offer the possibility to formulate rapid microbiological identification. The pattern of PJIs is evolving towards higher rates of MDR causes. During the last decade, a number of new antibiotic molecules with activity against MDRs have been approved. Some of them are also available either in oral formulation or as long-acting compounds, offering the opportunity for early patient's discharge, with expected healthcare costs saving.SummaryManagement of PJIs still represents a major threat for clinicians. Improvements in surgical techniques and antibiotic pipeline promise to revolutionize the approach in next years. Despite data from our experience confirm the efficacy of shorter antibiotic courses and the value of new molecules, randomized clinical trials are lacking. More data are needed in order to modify the routine clinical practice.mixedBassetti M.; Castaldo N.; Cadeo B.; Carnelutti A.Bassetti, M.; Castaldo, N.; Cadeo, B.; Carnelutti, A

Management of vertebral osteomyelitis in an 8-year period: the UDIPROVE (UDIne PROtocol on VErtebral osteomyelitis)

vertebral osteomyelitis (VO) is a compelling clinical entity for clinicians, because of its insidious and indolent course which make diagnosis difficult

TDM-guided therapy with daptomycin and meropenem in a morbidly obese, critically ill patient

OBJECTIVE: To describe a case of severe cellulitis, successfully treated with high-dose daptomycin plus continuous infusion meropenem, in a patient with morbid obesity and renal failure, in whom drug exposure over time was optimized by means of real-time therapeutic drug monitoring (TDM). CASE SUMMARY: A 63-year-old man with morbid obesity (body mass index 81.6 kg/m\ub2) and renal failure was admitted to the emergency department because of severe cellulitis. The patient had an admission Laboratory Risk Indicator for Necrotizing Fasciitis score of 9, and broad-spectrum antimicrobial therapy with daptomycin and meropenem was started. Because of rapidly changing renal function, dosage adjustments were guided by an intensive program of TDM (daptomycin ranging from 1200 mg every 48 hours over 30 minutes to 1200 mg every 36 hours over 30 minutes; meropenem ranging from 0.25 g every 8 hours over 6 hours to 500 mg every 4 hours by continuous infusion). Clinical response was observed within 72 hours. However, a sudden increase of serum creatine kinase (SCK) raised questions about the need for discontinuation of daptomycin. The drug concentrations were not toxic; therefore, we decided to continue therapy. Significant clinical improvement, with SCK normalization, was observed within a few days. Antimicrobial therapy was switched on day 29 to amoxicillin/clavulanate plus levofloxacin, and then discontinued at discharge on day 53. DISCUSSION: High-dose daptomycin plus continuous infusion meropenem may ensure adequate empiric antimicrobial coverage in patients with possible early necrotizing fasciitis. However, in patients with morbid obesity and changing renal function, significant challenges may arise because of the hydrophilic nature of these drugs and the inaccuracy of standard methods of estimating renal function. CONCLUSIONS: Real-time TDM may represent an invaluable approach in optimizing drug exposure with high-dose daptomycin plus continuous infusion meropenem in patients with severe cellulitis, morbid obesity, and changing renal function

Post-neurosurgical meningitis: Management of cerebrospinal fluid drainage catheters influences the evolution of infection

BACKGROUND: In order to better define the pathogenic role of cerebrospinal fluid (CSF) drainage catheters in postoperative patients, we comparatively analyze the clinical course of device and non-device-related meningitis. METHODS: This is an observational, partially prospective, study on consecutive adult patients who developed meningitis after undergoing neurosurgical procedures at the Neurosurgery and Neurointensive care Departments, Spedali Civili, Brescia, Italy, between January 1999 and August 2007. RESULTS: All 77 consecutive post-neurosurgical meningitis events in 65 patients were included in the analysis. Most were classified as external ventricular drainage (EVD)-related meningitis (23 cases, group A), external spinal drainage (ESD)-related meningitis (12 cases, group B), and non-device-related post-neurosurgical meningitis (30 cases, group C). Proven meningitis was identified in 78.3%, 91.7% and 56.7% of the events, respectively. ESD-related meningitis had a shorter onset time vs EVD and non-device-associated meningitis (3 days versus 6 and 7 days, respectively). Median antibiotic treatment duration was 20, 17, and 22.5 days in groups A, B, and C, respectively. Overall, 8 patients (34.8%) in group A, 3 (25.0%) in group B, and 3 (10.0%) in group C died. Median time to become afebrile was shorter in group C than in group A (10 days versus 12 days, P = 0.04). Removal of the device later than 48 hours after meningitis onset, as well as implantation of a second device were associated with a slower time of meningitis resolution. CONCLUSIONS: Early device removal and avoiding implantation of a second device were associated with short illness duration. Larger studies are warranted to confirm the conclusions of this study