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Background: Data comparing the clinical outcomes of novel β-lactam-β-lactamase inhibitors given in combination versus monotherapy for the treatment of multidrug-resistant (MDR) P. aeruginosa infections are lacking., Method: This retrospective cohort study included patients who received novel β-lactam-β-lactamase inhibitors as monotherapy or in combination for the treatment of MDR P. aeruginosa infections. The study was conducted between 2017 and 2022 in 6 tertiary care hospitals in Saudi Arabia. Overall in-hospital mortality, 30-day mortality, clinical cure, and acute kidney injury (AKI) were compared between recipients of monotherapy versus combination using multivariate logistic regression analysis., Result: 118 patients and 82 patients were included in monotherapy and combination therapy arms, respectively. The cohort represented an ill population with 56% in the intensive care unit and 37% in septic shock. A total of 19% of patients presented with bacteremia. Compared to monotherapy, combination therapy did not significantly differ in clinical cure (57% vs. 68%; P = 0.313; OR, 0.63; 95% CI, 0.36-1.14) in-hospital mortality (45% vs. 37%; P = 0.267; OR, 1.38; 95% CI, 0.78-2.45), or 30-day mortality (27% vs. 24%; P = 0.619; OR, 1.18; 95% CI, 0.62-1.25). However, AKI (32% vs. 12%; P = 0.0006; OR, 3.45; 95% CI, 1.67-7.13) was significantly more common in patients who received combination therapy., Conclusion: Novel β-lactam-β-lactamase inhibitors when used in combination with other antibiotics did not add clinical benefit compared to their use as monotherapy in the treatment of MDR P. aeruginosa infections. A Combination regimen was associated with an increased risk of nephrotoxicity., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Trimethoprim-sulfamethoxazole (TMP-SMX) has long been considered the treatment of choice for infections caused by Stenotrophomonas maltophilia. Levofloxacin has emerged as a potential option for treating these infections. This study aimed to evaluate the clinical outcomes in patients who received TMP-SMX versus levofloxacin for treating S. maltophilia infections., Methods: A retrospective, cohort study was conducted in 4 tertiary centres and included patients who were treated with either TMP-SMX or levofloxacin for infections caused by S. maltophilia. The main study outcomes were overall in-hospital mortality, 30-d mortality, and clinical cure. Safety outcomes were also evaluated. Multivariate analysis using logistic regression was used to control for the effect of the covariables., Results: We included 371 patients in this study, 316 received TMP-SMX and 55 patients received levofloxacin. A total of 70% were in the intensive care unit and 21% presented with bacteraemia. No statistically significant differences were observed in overall in-hospital mortality (52% vs. 40%; P = 0.113; odd ratio [OR], 1.59; 95% confidence interval [CI], 0.89-2.86), 30-d mortality (28% vs. 25%; P = 0.712; OR, 1.13; 95% CI, 0.59-2.18), or clinical cure (55% vs. 64%; P = 0.237; OR, 0.70; 95% CI, 0.37-1.31). Rates of acute kidney injury were comparable between the two groups (11% vs. 7%; P = 0.413)., Conclusion: Patients receiving levofloxacin for the treatment of infections caused by S. maltophilia demonstrated clinical outcomes similar to those receiving TMP-SMX. Our study suggests that levofloxacin can be a reasonable alternative to TMP-SMX to treat these infections., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The aim of this study was to compare the safety and effectiveness of monotherapy versus combination therapy for the treatment of infections caused by S. maltophilia ., Methods: This retrospective, multicenter, cohort study included patients treated with either monotherapy or combination therapy for infections caused by S. maltophilia . Primary outcomes included overall in-hospital mortality, 30-day mortality, and clinical cure. Safety outcomes were also evaluated. Multivariable logistic regression was used as a control for confounding variables., Results: A total of 407 patients were included, 330 patients received monotherapy and 77 patients received combination therapy. A total of 21% presented with concomitant bacteremia. After adjusting the differences between the two groups, there were no statistically significant differences between patients who received monotherapy versus combination therapy in clinical cure (55% vs 65%; OR, 0.72; 95% CI, 0.40-1.31) and overall in-hospital mortality (52% vs 49%; OR, 0.84; 95% CI, 0.45-1.57). However, patients who received monotherapy had a lower rate of 30-day mortality (28% vs 32%; OR, 0.45; 95% CI, 0.22-0.90) and acute kidney injury (9% vs 18%; OR, 0.35; 95% CI, 0.16-0.78)., Conclusion: Clinical outcomes did not significantly differ in patients who received combination therapy versus monotherapy. More data are needed to validate these findings.

Ceftolozane-tazobactam (C-T) and ceftazidime-avibactam (CAZ-AVI) are two novel antimicrobials that retain activity against resistant Pseudomonas aeruginosa. The comparative effectiveness and safety of C-T versus CAZ-AVI remain unknown. A retrospective, multicenter cohort study was performed in six tertiary centers in Saudi Arabia and included patients who received either C-T or CAZ-AVI for infections due to multidrug-resistant (MDR) P. aeruginosa. Overall in-hospital mortality, 30-day mortality, and clinical cure were the main study outcomes. Safety outcomes were also evaluated. A multivariate analysis using logistic regression was used to determine the independent impact of treatment on the main outcomes of interest. We enrolled 200 patients in the study (100 in each treatment arm). A total of 56% were in the intensive care unit, 48% were mechanically ventilated, and 37% were in septic shock. Approximately 19% of patients had bacteremia. Combination therapy was administered to 41% of the patients. The differences between the C-T and CAZ-AVI groups did not reach statistical significance in the overall in-hospital mortality (44% versus 37%; P  = 0.314; OR, 1.34; 95% CI, 0.76 to 2.36), 30-day mortality (27% versus 23%; P  = 0.514; OR, 1.24; 95% CI, 0.65 to 2.35), clinical cure (61% versus 66%; P  = 0.463; OR, 0.81; 95% CI, 0.43 to 1.49), or acute kidney injury (23% versus 17%; P  = 0.289; OR, 1.46; 95% CI, 0.69 to 3.14), even after adjusting for differences between the two groups. C-T and CAZ-AVI did not significantly differ in terms of safety and effectiveness, and they serve as potential options for the treatment of infections caused by MDR P. aeruginosa., Competing Interests: The authors declare no conflict of interest.

Background: Vancomycin is commonly used to treat methicillin-resistant staphylococcal infections in neonates. Consensus on its ideal dosing in neonates has not been achieved. Model-based dosing recently has evolved as an important tool to optimize vancomycin initial dosing. The aim of this is to evaluate a population pharmacokinetic model-based approach in achieving the vancomycin therapeutic target of an AUC 0-24 400 as recommended by the recent IDSA treatment guidelines. This model was implemented as a simple Excel calculator to individualize and optimize vancomycin initial dosing in neonates., Methods: An Excel calculator was developed using a previously published population pharmacokinetic model in neonates. It was evaluated using retrospectively retrieved data. For each patient, the initial empiric dose was calculated using the proposed Excel model and the most widely used neonatal dosing references. The probability of achieving the target AUC 0-24 of >400 mg h/L using the model-based method was calculated and compared with that of the empiric doses using other references., Results: This analysis included 225 neonates. The probability of achieving the target AUC 0-24 >400 was 89% using our model-based approach compared with 11%-59% using tertiary neonatal dosing references (p < 0.01 for all comparisons)., Conclusion: These innovative personalized dosing calculators are promising to improve vancomycin initial dosing in neonates and are easily applicable in routine practices., Competing Interests: Declaration of competing interest Manal Abouelkheir, Abdullah Almohaizeie, Abdulrahman Almutairi, Sara Almuhisen, Saeed Alqahtani and Abdullah Alsultan declare that they have no conflicts of interest., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Introduction: The relationship between cancers and thromboembolic events is well established. In our study, we aim to determine the burden of thromboembolic events in patients with solid tumors and identify the risk factors related to their development., Materials & Methods: Data on patients with solid tumors and thromboembolism between January 2013 and September 2014 were collected and analyzed., Results: During the study period 174 patients were identified. Of which, 172 (98.9%) had venous thrombus embolism, 137 (79%) were diagnosed with deep vein thromboses, 67 (38.5%) with pulmonary embolism, 84 (48.3%) were symptomatic and 90 (51.7) were incidental at diagnosis. The most common patients and disease characteristics were female sex, high body mass index (BMI), metastatic stage, colorectal and breast primaries, and anti-neoplastic therapy., Conclusion:  Our study confirmed the high burden of thromboembolic events in cancer patients and the relevant factors associated with its development., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Bazarbashi et al.)

Objectives: The aim of this study was to compare the safety and effectiveness of ceftolozane-tazobactam (C-T) to colistin-based regimen for treating infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa., Methods: This was a retrospective, multicentre, observational cohort study of inpatients who received either C-T or intravenous colistin for treating infections caused by MDR P. aeruginosa. The study was conducted in five tertiary care hospitals in Saudi Arabia. The main study outcomes included clinical cure at end of treatment, in-hospital mortality, and acute kidney injury (AKI). Univariate analysis and multivariate logistic regression model were conducted to evaluate the independent effect of C-T on the clinical outcome., Results: A total of 184 patients were included in the study: 82 patients received C-T, and 102 patients received colistin-based regimen. Clinical cure (77% vs. 57%; P = 0.005; OR, 2.52; 95% CI, 1.32-4.79) was significantly more common in patients who received C-T. After adjusting the difference between the two groups, treatment with C-T is independently associated with clinical cure (adjusted OR, 2.47; 95% CI, 1.16-5.27). In-hospital mortality (39% vs. 49%; P = 0.175; OR, 0.67; 95% CI, 0.37-1.20) was lower in patients who received C-T, but the difference was not significant. AKI (15% vs. 41%; P < 0.001; OR, 0.25; 95% CI, 0.12-0.51) was significantly less common in patients who received C-T., Conclusion: C-T is associated with a higher rate of clinical cure and lower rate of AKI compared to colistin. Our findings support the preferential use of C-T over colistin-based regimen for treating these infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)