Cefiderocol-containing regimens for the treatment of carbapenem-resistant A. baumannii ventilator-associated pneumonia: a propensity-weighted cohort study.

Background: Cefiderocol is a novel ß-lactam with activity against carbapenem-resistant Acinetobacter baumannii (CRAB), but its role in CRAB pulmonary infections is controversial due to limited evidence. Objectives: To assess the association between cefiderocol-containing regimens treatment and 28-day mortality in carbapenem-resistant A. baumannii ventilator-associated pneumonia (VAP). Methods: An observational cohort study including critically ill COVID-19 patients with CRAB-VAP admitted to two ICUs of a large academic hospital in Rome between September 2020 and December 2022. The primary outcome was 28-day all-cause mortality. A propensity score was created to balance the cefiderocol- and non-cefiderocol-containing groups. A propensity-weighted multiple logistic regression model was calculated to evaluate risk factors for 28-day mortality. Survival curves were calculated using the Kaplan-Meier method. Results: 121 patients were enrolled, 55 were treated with cefiderocol- and 66 with non-cefiderocol-containing regimens. The 28-day all-cause mortality was 56% (68/121). A statistically significant difference in 28-day mortality was found between cefiderocol- and non-cefiderocol- containing regimens groups (44% versus 67%, P = 0.011). In the propensity-adjusted multiple logistic regression, cefiderocol (OR 0.35 95% CI 0.14, 0.83) was a predictor of 28-day survival, Charlson comorbidity index (OR 1.36 95% CI 1.16, 1.78), SOFA score (OR 1.24 95% CI 1.09, 1.57) and septic shock (OR 3.71 95% CI 1.44, 12.73) were all associated with increased 28-day mortality. Conclusion: Cefiderocol-containing regimens were associated with reduced 28-day mortality in CRAB-VAP. The sample size and the observational design limit the study's conclusions. Future RCTs are needed to establish cefiderocol's definite role in these infections.

Empiric Antifungal Therapy for Intra-Abdominal Post-Surgical Abscesses in Non-ICU Patients.

The role of empiric antifungals for post-surgical abscesses (PSAs) is controversial, and international guidelines on invasive mycoses focus on bloodstream infections. We analyzed a retrospective cohort of 319 patients with PSA at a tertiary-level hospital in Italy during the years 2013-2018. Factors associated with empiric antifungal administration were analyzed and compared with factors associated with fungal isolation from the abdomen. Forty-six patients (14.4%) received empiric antifungals (65.2% azoles). Candida was isolated in 34/319 (10.7%) cases, always with bacteria. Only 11/46 patients receiving empirical antifungals had abdominal Candida. Only 11/34 patients with a fungal isolate received empiric antifungal therapy. Upper GI surgery (OR: 4.76 (CI: 1.95-11.65), p = 0.001), an intensive care unit stay in the previous 90 days (OR: 5.01 (CI: 1.63-15.33), p = 0.005), and reintervention within 30 days (OR: 2.52 (CI: 1.24-5.13), p = 0.011) were associated with empiric antifungals in a multivariate analysis, while pancreas/biliary tract surgery was associated with fungal isolation (OR: 2.25 (CI: 1.03-4.91), p = 0.042), and lower GI surgery was protective (OR: 0.30 (CI: 0.10-0.89), p = 0.029) in a univariate analysis. The criteria for empiric antifungal therapy in our practice seem to be inconsistent with the risk factors for actual fungal isolation. Better guidance for empiric therapy should be provided by wider studies.

A review of recent advances in the treatment of adults with complicated urinary tract infection.

INTRODUCTION: Complicated urinary tract infections (cUTIs) entail diverse clinical conditions that could be managed differently and not necessarily with premature empiric therapy. Since multidrug-resistant organisms (MDROs) are widely spreading worldwide, the possibility of encountering these resistant bacteria is inevitably part of the daily life of physicians who manage cUTIs. AREAS COVERED: The advances in the management of cUTIs are explored, illustrating: 1) a proposed therapeutical approach to cUTIs within the antimicrobial stewardship context; 2) evidence regarding novel antibiotics targeting MDROs. Evidence research has been performed through MEDLINE/PubMed using appropriate keywords and terms regarding cUTIs published before June 2022. EXPERT OPINION: Novel antimicrobial drugs are available in the clinicians' armamentarium. Selecting the optimal therapy for suitable patients may be challenging given the multifaceted group of cUTIs. Carbapenems use is widely increasing, the role of old ß-lactam/ß-lactamase inhibitors is constantly revised, and novel drugs lack real-life studies. Understanding the different ranges of the complexity of patients affected by cUTIs may help select the most suitable antibiotic for every single case. More multicentric observational studies targeting cUTIs are needed to elucidate the appropriate drug based on patient characteristics and presentations, providing stronger recommendations for cases encountered in everyday clinical practice.

Post-Prescription Audit Plus Beta-D-Glucan Assessment Decrease Echinocandin Use in People with Suspected Invasive Candidiasis.

Background and Objectives: Overtreatment with antifungal drugs is often observed. Antifungal stewardship (AFS) focuses on optimizing the treatment for invasive fungal diseases. The objective of the present study was to evaluate the utility of a post-prescription audit plus beta-D-glucan (BDG) assessment on reducing echinocandin use in persons with suspected invasive candidiasis. Materials and Methods: This is a prospective, pre-post quasi-experimental study of people starting echinocandins for suspected invasive candidiasis. The intervention of the study included review of each echinocandin prescription and discontinuation of treatment if a very low probability of fungal disease or a negative BDG value were found. Pre-intervention data were compared with the intervention phase. The primary outcome of the study was the duration of echinocandin therapy. Secondary outcomes were length of hospital stay and mortality. Results: Ninety-two echinocandin prescriptions were reviewed, 49 (53.3%) in the pre-intervention phase and 43 (46.7%) in the intervention phase. Discontinuation of antifungal therapy was possible in 21 of the 43 patients in the intervention phase (48.8%). The duration of echinocandin therapy was 7.4 (SD 4.7) in the pre-intervention phase, 4.1 days (SD 2.9) in persons undergoing the intervention, and 8.6 (SD 7.3) in persons in whom the intervention was not feasible (p at ANOVA = 0.016). Length of stay and mortality did not differ between pre-intervention and intervention phases. Conclusions: An intervention based on pre-prescription restriction and post-prescription audit when combined with BDG measurement is effective in optimizing antifungal therapy by significantly reducing excessive treatment duration.

Predictors of mortality among adult, old and the oldest old patients with bloodstream infections: An age comparison.

BACKGROUND: Bloodstream infections (BSIs) are a major cause of mortality in elderly. Objective of the study is to identify factors predictive of mortality in old and oldest old patients. METHODS: This is a single centre retrospective observational study, including all patients admitted to Fondazione Policlinico A. Gemelli university hospital and diagnosed with BSI. Patients were stratified into three groups according to age: adult (A), younger than 65; old (O), aged between 65 and 80; oldest old (OO), older than 80. Primary outcome was 30-day in-hospital mortality. Secondary outcomes were duration of antimicrobial therapy (DOT) and length of hospital stay (LOS). RESULTS: Of the 1034 patients included in the study, 346 were in group A, 447 in group O and 241 in group OO. The rate of 30-day mortality raised from 6.9% (24/346) in group A to 10.8% (84/447) in group O and 33.2% (80/241) in group OO (p<0.01), while DOT and LOS significantly decreased moving from adults to oldest old (p<0.01). Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus spp were both independently correlated to an increased 30-day mortality risk selectively in patients older than 80 (MRSA: HR 2.37, p=0.03; Enterococcus spp: HR 2.44, p=0.01). CONCLUSIONS: BSIs have a high impact on survival in old and oldest old patients. BSIs by gram-positive pathogens, in particular MRSA and Enterococcus spp, should be a wake-up call for physicians, who should focus efforts on adequate and prompt antibiotic and support treatment.

Antibiotic appropriateness and adherence to local guidelines in perioperative prophylaxis: results from an antimicrobial stewardship intervention.

OBJECTIVES: Surgical antibiotic prophylaxis (SAP) represents a major indication of antibiotic consumption worldwide. The present study aims to report the results of an enabling, long-term AMS intervention conducted between 2013 and 2019 on an Italian University Hospital performing more than 40.000 surgical interventions per year. METHODS: SAP inappropriateness was defined according to the ASHP guidelines and divided in four main categories: indication, selection and dosing, duration, timing. Between 2013 and 2019, we conducted a continuative AMS intervention over 14 surgical departments that included enablement, review of selected clinical records and feedback. RESULTS: We collected a total of 789 SAP prescribed to 735 patients (mean age 56.7 ± 17.8y). Overall, guideline adherence improved from 36.6% (n = 149) at baseline to 57.9% (n = 221) post-intervention (P <  0.0001). A significant improvement (P <  0.001) was also detected for each category: indication (from 58.5 to 93.2%), selection and dosing (from 58.5 to 80.6%), timing (from 92.4 to 97.6%), duration (from 71 to 80.1%). CONCLUSIONS: Though results cannot be generalized to all hospital populations, enabling AMS interventions may be effective in establishing a sustained improvement in SAP appropriateness rates. Once identified the main causes of SAP inappropriateness, tailored AMS interventions for each department may be beneficial. Further studies are needed to evaluate specific outcomes as incidence of surgical site infections and antimicrobial resistance.

Day 10 Post-Prescription Audit Optimizes Antibiotic Therapy in Patients with Bloodstream Infections.

This study aimed to investigate the clinical and organizational impact of an active re-evaluation (on day 10) of patients on antibiotic treatment diagnosed with bloodstream infections (BSIs). A prospective, single center, pre-post quasi-experimental study was performed. Patients were enrolled at the time of microbial BSI confirmation. In the pre-intervention phase (August 2014-August 2015), clinical status and antibiotic regimen were re-evaluated at day 3. In the intervention phase (January 2016-January 2017), clinical status and antibiotic regimen were re-evaluated at day 3 and day 10. Primary outcomes were rate of optimal therapy, duration of antibiotic therapy, length of hospitalization, and 30-day mortality. A total of 632 patients were enrolled (pre-intervention period, n = 303; intervention period, n = 329). Average duration of therapy reduced from 18.1 days (standard deviation (SD), 11.4) in the pre-intervention period to 16.8 days (SD, 12.7) in the intervention period (p < 0.001). Similarly, average length of hospitalization decreased from 24.1 days (SD, 20.8) to 20.6 days (SD, 17.7) (p = 0.001). No inter-group difference was found for the rate of 30-day mortality. In patients with BSI, re-evaluation of clinical status and antibiotic regimen at day 3 and 10 after microbiological diagnosis was correlated with a reduction in the duration of antibiotic therapy and hospital stay. The intervention is simple and has a low impact on overall costs.

Management and prevention of cranioplasty infections.

BACKGROUND: Infection may complicate the outcome of cranial repair with significant additional morbidity, related to hospitalization, surgery and long antibiotic therapy, that may become even dramatic in case of multi-resistant germs and in particular in the paediatric population. Additionally, the economic costs for the health system are obvious. Moreover, surgical decisions concerning the timing of cranioplasty and choice of the material may be strongly affected by the risk of infection. Despite, management and prevention of cranioplasty infections are not systematically treated through the literature so far. METHODS: We reviewed pertinent literature dealing with cranioplasty infection starting from the diagnosis to treatment options, namely conservative versus surgical ones. Our institutional bundle, specific to the paediatric population, is also presented. This approach aims to significantly reduce the risk of infection in first-line cranioplasty and redo cranioplasty after previous infection. CONCLUSIONS: A thorough knowledge and understanding of risk factors may lead to surgical strategies and bundles, aiming to reduce infectious complications of cranioplasty. Finally, innovation in materials used for cranial repair should also aim to enhance the antimicrobial properties of these inert materials.

Performance evaluation of the (1,3)-ß-D-glucan detection assay in non-intensive care unit adult patients.

OBJECTIVES: To assess the performance of the (1,3)-ß-D-glucan (BDG) detection assay in a large cohort of patients with suspected candidemia who were admitted to non-intensive care unit hospital wards. METHODS: This observational, retrospective cohort study was conducted in a 1,100-bed university hospital in Rome, where an infectious disease consultation team has been operational. Two groups of patients were included in the analysis: Group 1, patients with Candida bloodstream infection (BSI) who had at least one BDG test performed ±48 hours from the first positive blood culture (Candida BSI Group) and Group 2, patients with risk factors for candidemia who had at least one BDG test but had negative blood cultures (Control Group). Both Group 1 and Group 2 did not receive prior antifungal therapy. Different BDG cutoff values were considered: 80, 200, 300, 400, and ≥500 pg/mL. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated. RESULTS: A total of 1,296 patients were studied. Of them, 100 patients (candidemic) were in Group 1 and the remaining 1,196 patients (controls) were in Group 2. There were no differences in demographic characteristics between patients of the two groups. According to the above cutoff values, sensitivity (%) and specificity (%) of the BDG assay ranged from 91 to 60.7 and 87.7 to 97.8, respectively, whereas the PPV (%) and NPV (%) ranged from 38.2 to 68.3 and 99.1 to 97.0, respectively. CONCLUSION: Serum BDG has a very high NPV in a population with10% prevalence of candidemia. This NPV may support decisions to discontinue antifungal therapy in those patients who were empirically treated because of the suspect of candidemia.

Systematic clinical management of patients with candidemia improves survival.

OBJECTIVES: Taking into account the significant morbidity, mortality, and hospital costs related to Candidemia, our objective is to define if improving appropriateness in candidemia management was associated with better clinical outcomes. METHODS: A prospective observational monocentric cohort study was conducted. Adherence to five main elements was examined: appropriate selection of initial therapy; follow-up blood culture; echocardiography; ophthalmological examination; and removal of a central venous catheter. The correlation between the number of appropriate elements achieved and 30 day survival was examined. RESULTS: Patients with candidemia (n = 213) were enrolled. Adherence to all five elements was achieved in 36 cases (16.9%), while the majority adhered to three or four elements (28.2% and 37.1%, respectively). Multivariable Cox regression analysis revealed that the number of elements achieved was associated with survival [HR: 0.39 (0.30-0.52); p < 0.001]. Also, the number of elements achieved correlated positively with duration of therapy (p = 0.01), but not length of hospital stay (p = 0.56). CONCLUSIONS: Five elements, including therapeutic and non-therapeutic-related aspects, of care were good indicators of appropriate management of patients with candidemia. Implementation of evidence-based practice regarding optimal clinical management is crucial for any antimicrobial stewardship program.

Incidental intraoperative diagnosis of Mycobacterium abscessus meningeal infection: a case report and review of the literature.

PURPOSE: Mycobacterium abscessus, and rapidly growing mycobacteria in general, are rare but increasing causes of central nervous system (CNS) infections. The aim of this study is to highlight the importance of considering these microorganism in the differential diagnosis of CNS infections, obtaining a prompt diagnosis, and improving clinical outcomes. METHODS: Case report and literature review. RESULTS: We report a case of meningeal infection in a patient who underwent decompressive craniectomy after a craniofacial trauma. The diagnosis was made analyzing a sample obtained during a second operation of cranioplasty. A regimen of amikacin, clarithromycin, and imipenem/cilastatin was started. In the following days, the patient experienced a variety of side effects. So, first clarithromycin was replaced with linezolid, then amikacin was stopped and cefoxitin added to the therapy and at the end all the antibiotics were withdrawn. The patient was discharged in good conditions and a clinical interdisciplinary follow-up was started. After 12 months, the patient is still doing well. After a literature analysis, 15 cases of M. abscessus CNS infections were identified. Various modes of acquisition, underlying disease and therapeutic schemes were evident. CONCLUSIONS: Considering the results of the literature analysis and the increasing incidence of M. abscessus, all specialists involved in the management of CNS infection should be aware of the importance of atypical microorganisms in differential diagnosis.

Trimethoprim-sulfamethoxazole therapy for patients with carbapenemase-producing Klebsiella pneumoniae infections: retrospective single-center case series.

OBJECTIVE: The objective of the study was to evaluate the efficacy and tolerability of trimethoprim-sulfamethoxazole (also known as co-trimoxazole, TMPS) to treat Klebsiella pneumoniae (Kp)-K. pneumoniae carbapenemase (KPC) infections. METHODS: Clinical data of patients with a TMPS-susceptible Kp-KPC infection were collected as a case series. RESULTS: We report clinical outcomes and tolerability for 14 patients infected by Kp-KPC strains susceptible to TMPS, including three bloodstream infections. In ten cases (71.4%), TMPS was administered as monotherapy. In all but one case, Kp-KPC infection was cured. In the remaining patient, therapy was discontinued because of an adverse event. CONCLUSIONS: The use of TMPS to treat TMPS-susceptible Kp-KPC infections seems promising.

Impact of antibiotic stewardship on perioperative antimicrobial prophylaxis.

OBJECTIVE: Antibiotic prophylaxis (AP) is useful to prevent antimicrobial overuse, misuse and abuse, as well against the occurrence of surgical site infections (SSIs). This study aimed to describe the implementation of a quality improvement intervention on AP for elective surgery, as informal interviews showed a lower than expected compliance with internal recommendations, and to evaluate intervention's effect in terms of main drug consumption. DESIGN: A quality improvement intervention on all elective cases within 14 main surgical departments was performed. SQUIRE 2.0 guidelines were used in designing and reporting. SETTING: The intervention was implemented in an Italian Teaching Hospital 2 years after the adoption of internal evidence-based AP recommendations. PARTICIPANTS: Professionals involved in elective surgery. INTERVENTIONS: The intervention was structured into two phases: a survey was conducted during two non-consecutive weeks period (April-May 2013) to assess the adherence to the international guidelines in AP; survey's results were presented and discussed with all the surgical teams (December 2013-April 2014). MAIN OUTCOME MEASURES: Impact on cefazolin consumption (in defined daily doses per 100 procedures). RESULTS: Data of AP for 653 surgical procedures in terms of type, timing, duration, excess and defect were analyzed. An optimal AP rate resulted in 48.1% cases. Reduction in cefazolin use (-21.5%) and cost (-22.9%) was registered. CONCLUSIONS: Though results cannot be generalized to all hospital populations, the implemented intervention is likely to improve AP consequently improving quality of care and reducing costs. Further studies are needed to evaluate specific outcomes such as rate of SSIs and antibiotic resistance.