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Background Metallo-β-lactamase (MBL)–producing Enterobacterales are increasing worldwide. Our aim was to describe clinical features, treatments, and outcomes of infections by MBL-Enterobacterales. Methods A prospective observational study conducted in the Pisa University Hospital (January 2019 to October 2022) included patients with MBL-producing Enterobacterales infections. The primary outcome measure was the 30-day mortality rate. Multivariable Cox regression analysis was performed to identify factors associated with that mortality rate, and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated. Results The study's 343 patients included 15 with Verona integron-encoded MBL (VIM)- and 328 with New Delhi MBL (NDM)–producing Enterobacterales infections; there were 199 patients (58%) with bloodstream infections, 60 (17.5%) with hospital-acquired or ventilator-associated pneumonia, 60 (17.5%) with complicated urinary tract infections, 13 (3.8%) with intra-abdominal infections, and 11 (3.2%) with skin and soft-tissue infections. The 30-day mortality rate was 29.7%. Of 343 patients, 32 did not receive in vitro active antibiotic therapy, 215 (62.7%) received ceftazidime-avibactam plus aztreonam, 33 (9.6%) received cefiderocol-containing regimens, 26 (7.6%) received colistin-containing regimens, and 37 (10.8%) received other active antibiotics. On multivariable analysis, septic shock (aHR, 3.57 [95% CI, 2.05–6.23]; P <.001) and age (1.05 [1.03–1.08]; P <.001) were independently associated with the 30-day mortality rate, while in vitro active antibiotic therapy within 48 hours after infection (0.48 [.26–.8]; P =.007) and source control (0.43 [.26–.72]; P =.001) were protective factors. Sensitivity analysis showed that ceftazidime-avibactam plus aztreonam, compared with colistin, was independently associated with a reduced 30-day mortality rate (aHR, 0.39 [95% CI,.18–.86]; P =.02). Propensity score analyses confirmed these findings. Conclusions MBL-producing carbapenem-resistant Enterobacterales infections are associated with high 30-day mortality rates. Patients with MBL-producing Enterobacterales infections should receive early active antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background In vitro–in vivo discordance in β-lactams' activities against metallo-ß-lactamase (MBL)-producing Enterobacterales has been described. We aimed to assess whether this discordance is attributed to the supra-physiologic zinc concentration in in vitro testing media. Methods A clinical and microbiological observational study of patients with bloodstream infections due to New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae was performed. Outcomes of patients treated empirically with non-MBL-active β-lactam therapy (carbapenems and ceftazidime/avibactam) and MBL-active β-lactam therapy (ceftazidime/avibactam + aztreonam) were documented. The patients' isolates were used to induce septicemia in mice, and survival upon meropenem treatment was recorded. Meropenem minimum inhibitory concentrations (MICs) were determined in standard media and in the presence of physiological zinc concentrations. Results Twenty-nine patients receiving empiric non-MBL-active β-lactams (median duration, 4 days) were compared with 29 receiving MBL-active β-lactams. The 14-day mortality rates were 21% and 14%, respectively. In the murine septicemia model, meropenem treatment resulted in protection from mortality (P <.0001). Meropenem MICs in the physiologic zinc concentration broth were 1- to >16-fold lower vs MICs in zinc-unadjusted broth (≥64 mg/L). Conclusions Our data provide foundational support to establish pharmacokinetic/pharmacodynamic relationships using MICs derived in physiologic zinc concentration, which may better predict β-lactam therapy outcome. [ABSTRACT FROM AUTHOR]

Meropenem/vaborbactam plus aztreonam as a possible treatment strategy for bloodstream infections caused by ceftazidime/avibactam-resistant Klebsiella pneumoniae: a retrospective case series and literature review. Future studies are needed to compare the MER/VAB+ATM combination with CAZ/AVI+ATM in MBL-producing Kp infections. Metallo- -lactamase (MBL)-producing I Klebsiella pneumoniae i (Kp) is increasingly reported in Europe and the United States, and limited treatment options are available against this superbug.[[1], [3], [5]] MBLs hydrolyse all -lactams except aztreonam, but this latter cannot be used as monotherapy because of the co-production of expanded-spectrum- -lactamases (ESBL). [Extracted from the article]

Novel vectors, with selection based on expression of hygromycin resistance, facilitated the transformation of such mycobacterial species as Mycobacterium smegmatis and Mycobacterium bovis BCG. The hygromycin resistance vector exhibited greater efficiency than kanamycin resistance vectors. Hygromycin resistance may be used as a selectable marker in novel recombinant mycobacterial variances.

Background In vitro data support the use of combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI), but clinical studies are lacking. The aim of our study was to compare the outcome of patients with bloodstream infections (BSIs) due to metallo-β-lactamase (MBL)–producing Enterobacterales treated either with CAZ-AVI plus ATM or other active antibiotics (OAAs). Methods This was a prospective observational study including patients admitted to 3 hospitals in Italy and Greece. The primary outcome measure was 30-day all-cause mortality. Secondary outcomes were clinical failure at day 14 and length of stay after BSI diagnosis. Cox regression analysis including a propensity score (PS) for receiving CAZ-AVI + ATM was performed to evaluate primary and secondary outcomes. A PS-based matched analysis was also performed. Results We enrolled 102 patients with BSI; 82 had infections caused by NDM-producing (79 Klebsiella pneumoniae and 3 Escherichia coli) and 20 by VIM-producing (14 K. pneumoniae , 5 Enterobacter species, 1 Morganella morganii) strains. The 30-day mortality rate was 19.2% in the CAZ-AVI + ATM group vs 44% in the OAA group (P  = .007). The PS-adjusted analysis showed that the use of CAZ-AVI + ATM was associated with lower 30-day mortality (hazard ratio [HR], 0.37 [95% confidence interval {CI},.13–.74]; P  = .01), lower clinical failure at day 14 (HR, 0.30 [95% CI,.14–.65]; P  = .002), and shorter length of stay (subdistributional HR, 0.49 [95% CI,.30–.82]; P  = .007). The PS-matched analysis confirmed these findings. Conclusions The CAZ-AVI + ATM combination offers a therapeutic advantage compared to OAAs for patients with BSI due to MBL-producing Enterobacterales. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Ten critically ill patients with either bacteremia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii , Stenotrophomonas maltophilia , or New Delhi metallo-β-lactamase–producing Klebsiella pneumoniae received cefiderocol. All strains had minimum inhibitory concentration ≤2 μg/mL. Thirty-day clinical success and survival rates were 70% and 90%, respectively. Two patients had a microbiological failure. Future prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19.Objectives: To identify predictors of superinfections in COVID-19.Methods: Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections.Results: Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11-29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5-39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4-13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2-11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7-7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1-7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445).Conclusions: The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced. [ABSTRACT FROM AUTHOR]