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Background Clostridioides difficile infection (CDI), a leading cause of nosocomial deaths, is a microbiota-mediated disease. As such, the use of broader spectrum antibiotics, such as vancomycin and metronidazole, can prime the gastrointestinal tract to become more prone to CDI recurrences. Fidaxomicin, a narrow-spectrum antibiotic, has been demonstrated to be superior in preventing recurrence and in preserving the intestinal microbiota; however, widespread employment worldwide has been hindered due to high acquisition costs. Objectives To integrate the currently available guidelines on the management of CDI and to shed light on the timeliest employment of fidaxomicin. Methods An expert panel was gathered to obtain consensus using Delphi methodology on a series of statements regarding the management of CDI and on appropriate antibiotic use. Results Consensus was reached on 21 of the 25 statements addressing the management of CDI. Conclusions Delphi methodology was used to achieve consensus on the management of CDI, on the identification of patients at risk of recurrences or severe infection, and on the most appropriate use of fidaxomicin, with the final aim of fostering clinical practice application of treatment algorithms proposed by previous guidelines, in absolute synergy. It could be an important tool to promote more appropriate and cost-effective CDI treatments in European settings with limited resources, like Italy. [ABSTRACT FROM AUTHOR]

Background Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam. Methods We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least ≥24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality. Results The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index ≥ 3, dialysis, concomitant COVID-19, and INCREMENT score ≥ 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy. Conclusions Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy. [ABSTRACT FROM AUTHOR]

Bacterial resistance mechanisms are continuously and rapidly evolving. This is particularly true for Gram-negative bacteria. Over the last decade, the strategy to develop new β-lactam/β-lactamase inhibitors (BLs/BLIs) combinations has paid off and results from phase 3 and real-world studies are becoming available for several compounds. Cefiderocol warrants a separate discussion for its peculiar mechanism of action. Considering the complexity of summarizing and integrating the emerging literature data of clinical outcomes, microbiological mechanisms, and pharmacokinetic/pharmacodynamic properties of the new BL/BLI and cefiderocol, we aimed to provide an overview of data on the following compounds: aztreonam/avibactam, cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, cefiderocol, ceftaroline/avibactam, ceftolozane/tazobactam, ceftazidime/avibactam, imipenem/relebactam, meropenem/nacubactam and meropenem/vaborbactam. Each compound is described in a dedicated section by experts in infectious diseases, microbiology, and pharmacology, with tables providing at-a-glance information. [ABSTRACT FROM AUTHOR]

Background A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. Methods We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. Results The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P =.79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P =.002), neutropenia (P <.001), or an INCREMENT score ≥8 (P =.01); with lower respiratory tract infection (LRTI) (P =.04); and with CAZ-AVI dose adjustment for renal function (P =.01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P =.006). All associations remained significant after propensity score adjustment. Conclusions CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 21-year-old female lung transplant patient who developed disseminated nocardiosis, a rare bacterial infection. The patient was initially treated with a combination of antibiotics but experienced adverse effects with one of the drugs. The treatment was then switched to tedizolid, an antibiotic that had not been previously studied for nocardiosis. The article describes how the dosage of tedizolid was adjusted based on therapeutic drug monitoring and pharmacogenetic analysis. The patient showed improvement with the higher dosage of tedizolid and had no recurrence of infection. The article concludes that tedizolid, with TDM and pharmacogenetic analysis, may be a viable alternative for the treatment of nocardiosis in lung transplant patients. [Extracted from the article]

Background Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary tract infections, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against Klebsiella pneumoniae carbapenemase (KPC) enzyme producers, but clinical trial data on its efficacy in this setting are lacking. Methods We retrospectively reviewed 138 cases of infections caused by KPC-producing K. pneumoniae (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic. Results The 138 patients started CAZ-AVI salvage therapy after a first-line treatment (median, 7 days) with other antimicrobials. CAZ-AVI was administered with at least 1 other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs 55.8%, P =.005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival. Conclusions CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia. [ABSTRACT FROM AUTHOR]

Background Few data exist on clinical characteristics, therapeutic management and outcome of patients with Non-Fermenting Gram-negative bloodstream infection (NFGN-BSI). Our aim is to describe a large cohort of patients with NFGN-BSI and to investigate risk factors for 30-day mortality. Further, the impact of the new difficult to treat resistance (DTR) definition will be investigated. Methods Retrospective multicenter study of patients diagnosed with NFGN-BSI at three large Italian hospitals (Bologna, Genova, Torino), over a 4-year period (2013–2016). Exclusion criteria: age <18 years, clinical data not available, polymicrobial BSI, death within 72 hours from drawing index blood cultures (BCs). Carbapenem resistance (CR) was defined according to 2015 CDC definitions, and DTR as resistance to all β-lactams and fluoroquinolones. Active empiric therapy (AET) was defined as at least one in vitro active drug administered within 24 hours from drawing index BCs. Endpoint was all-cause 30-day mortality. Results 521 patients with NFGN-BSI were analyzed: 63.3% male, median age 67 (IQR 55–78) years, median Charlson index 6 (IQR: 3–7). Most episodes were hospital acquired 72.9%. Etiology distribution: Pseudomonas aeruginosa 69.9%, Acinetobacter baumannii 19.6%, and Stenotrophomonas maltophilia 10.6%. CR and DTR rates were 38.6% and 26.9%. Main infection sources were deemed as primary 50.7%, CVC-related 26.5%, and lower respiratory tract 16.3%. Source control and ID consultation were performed in 33.4% and 47.6% of cases. AET rate was 38.2%. Empiric and definitive antibiotic treatment cohorts consisted of 377 and 472 patients, respectively. There was high heterogeneity in antibiotic choice with 30 and 48 different regimens in empiric and definitive cohort, respectively. Combination therapy was administered in 22.3% of empiric cohort and in 37.3% of definitive cohort patients. Independent risk factors for 30-day mortality were age (HR 1.03, 95% CI 1.01–1.05, P = 0.001), SOFA (HR 1.25, 1.15–1.36, <0.001), DTR (HR 2.73, 1.60–4.65, <0.001), and AET (HR 0.50, 0.25–0.99, 0.05). Conclusion High heterogeneity in therapeutic management of patients with NF-GNBSI was observed. DTR was a strong predictor of mortality, AET was associated with improved outcome. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram-negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited., Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≤72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events., Results: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P. aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia ( n = 20; 48.8%), primary bacteremia ( n = 7; 17.1%), intra-abdominal infection ( n = 4; 9.8%), and bone infection ( n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment ( n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population., Conclusions: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE., Competing Interests: M.B. serves on scientific advisory boards for Angelini, AstraZeneca, Bayer, Cubist, Pfizer, Menarini, MSD, Nabriva, Paratek, Roche, Shionogi, Tetraphase, The Medicine Company, and Astellas Pharma Inc.; has received funding for travel or speaker honoraria from Algorithm, Angelini, Astellas Pharma Inc., AstraZeneca, Cubist, Pfizer MSD, Gilead Sciences, Menarini, Novartis, Ranbaxy, Teva. The other authors declare no conflicts of interest.