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While previous studies have focused on the technical aspects of groundwater extraction and optimal cropping patterns, there is a notable lack of research on the socio-economic factors affecting groundwater access and agricultural productivity, especially at a micro-level in Punjab, India. This study, therefore, investigates the water use efficiency (WUE) and economic water productivity (EWP) of paddy and wheat crops across diverse farm sizes and districts in Punjab, offering critical insights into agricultural water management. The study is based on primary data from Punjab, India, with Sangrur, Jalandhar, Pathankot, and Bathinda districts selected for groundwater profile analysis via multistage random sampling of 246 farmers. Notably, Punjab exhibits high EWP for wheat, surpassing the national average. However, disparities exist across districts, emphasizing the importance of localized interventions. Larger farms consistently demonstrate higher WUE and EWP, underlining the significance of scale in optimizing water inputs. Factors such as farm size, crop variety, and regional variations significantly influence WUE and EWP. Tailored approaches for marginal farmers and districts with lower efficiency are crucial for promoting sustainable agricultural practices. The findings underscore the need for targeted policy interventions to enhance water use efficiency and productivity in Punjab's agriculture sector. [ABSTRACT FROM AUTHOR]

The Punjab Preservation of Subsoil Water Act 2009 is a legislative measure introduced to address the critical issue of groundwater depletion in Punjab, India. This research examines the implications of this Act and the rising groundwater scarcity in Punjab. Using qualitative research methods, including GIS mapping, it evaluates the postimplementation impact of the Act on groundwater conservation and water availability and assesses its effectiveness in achieving its objectives. This study reveals that the government's policies favoring wheat and rice have significantly contributed to the expansion of these crops, resulting in imbalanced agricultural practices. While the overall groundwater development in Punjab decreased from 170% in 2009 to 165% in 2017, a district-wise analysis reveals that the fall in the groundwater exploitation level in seven districts outperforms the rise in the exploitation level in the other thirteen districts of the state, showing overall minor or no improvement. This study proposes a multifaceted approach combining command-and-control measures with self-regulation incentives. It highlights the potential of incentivizing farmers to adopt sustainable practices, diversify crops, and implement water-efficient technologies. This paper also suggests the importance of involving stakeholders and the community in groundwater management, emphasizing the need for participatory approaches to ensure the long-term sustainability of water resources. While this study provides valuable insights, it is essential to acknowledge that its scope is limited to a qualitative assessment, and there may be challenges in generalizing the findings to all regions facing groundwater depletion. [ABSTRACT FROM AUTHOR]

Background Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin. Methods Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied. Results Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, –5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P =.034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P =.001). Conclusions No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required. [ABSTRACT FROM AUTHOR]

Background Mounting evidence suggests the addition of a β-lactam (BL) to daptomycin (DAP) results in synergistic in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and bolsters the innate immune response to infection. This study's objective was to provide clinical translation to these experimental data and determine if DAP+BL combination therapy results in improved clinical outcomes compared with treatment with DAP alone in patients with MRSA bloodstream infections (BSIs). Methods This was a retrospective, comparative cohort study conducted at 2 academic medical centers between 2008 and 2018. Adults with MRSA BSI treated with DAP for ≥72 hours and initiated ≤5 days of culture collection were included. Patients who received a BL for ≥24 hours and initiated ≤24 hours of DAP comprised the DAP+BL group. The primary outcome was composite clinical failure (60-day all-cause mortality and/or 60-day recurrence). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). Results A total of 229 patients were included (72 DAP+BL and 157 DAP). In unadjusted and IPTW-adjusted analyses, DAP+BL was associated with significantly reduced odds of clinical failure (odds ratio [OR], 0.362; 95% confidence interval [CI],.164–.801; adjusted OR, 0.386; 95% CI,.175–.853). Adjusted analyses restricted to prespecified subgroups based on infection complexity and baseline health status were consistent with the main analysis. Conclusions The addition of a BL to DAP was associated with improved clinical outcomes in patients with MRSA BSI. This study provides support to ongoing and future studies evaluating the impact of combination therapy for invasive MRSA infections. Patients treated with daptomycin plus a β-lactam for MRSA bloodstream infection had lower odds of composite clinical failure defined as 60-day all-cause mortality and/or 60-day recurrence compared with patients treated with daptomycin monotherapy after adjusting for confounding variables using inverse probability of treatment weighting. [ABSTRACT FROM AUTHOR]

Background: Published guidelines call for prolonged courses of intravenous (iv) antibiotics for the treatment of MRSA bloodstream infection (BSI) to ensure eradication of deep foci and decrease relapse risk. Sequential iv-to-oral antibiotic therapy has been successfully applied to other serious infections but has not been evaluated for MRSA BSI.Objectives: To compare outcomes in adults completing MRSA BSI therapy with oral versus parenteral antibiotics in the outpatient setting [oral outpatient antibiotic therapy (OOAT) versus outpatient parenteral antibiotic therapy (OPAT)].Methods: This was a single-centre, retrospective, cohort study between 2008 and 2018. The primary outcome was 90 day clinical failure (MRSA BSI recurrence, deep-seated MRSA infection or all-cause mortality). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW).Results: A total of 492 patients were included (70 OOAT, 422 OPAT). In general, OOAT patients had characteristics consistent with a lower risk of poor outcomes; however, after IPTW key prognostic factors were balanced. In IPTW-adjusted analysis, there was non-significant reduction in the rate of 90 day clinical failure in the OOAT group compared with the OPAT group [adjusted HR (aHR) 0.379, 95% CI 0.131-1.101]. In analyses restricted to pre-specified subgroups defined by index infection complexity and comorbidity burden, findings were consistent with the main analysis. Furthermore, OOAT patients had a significantly reduced rate of 90 day hospital readmission (aHR 0.603, 95% CI 0.388-0.937).Conclusions: We provide preliminary evidence that selected patients with MRSA BSI may have at least equivalent clinical outcomes with OOAT versus OPAT and provide support to ongoing and future studies evaluating oral antibiotics for MRSA BSI. [ABSTRACT FROM AUTHOR]

Background Ceftazidime–avibactam (CZA) is a novel cephalosporin/β-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae (CRE) and multidrug-resistant (MDR) Pseudomonas aeruginosa (PA). Real-world experience with CZA for CRE infections is accumulating but data on its use for MDR PA infections remains limited. Methods Retrospective, multicenter cohort study describing the clinical characteristics and outcomes of patients treated with CZA (≥ 72 hours) for MDR PA infections between 2015 and 2018. Results Fifty-one patients were included. The median (IQR) age was 61 (43, 71) years. Most patients had MDR risk factors including recent hospitalization (74.5%), recent antimicrobial exposure (84.3%), and/or previous infection or colonization with an MDR pathogen (58.8%). The median Charlson Comorbidity score was 4 (2, 6) and the median APACHE II score was 20 (12, 29). Infections were predominantly (68.6%) hospital-acquired and 52.9% of patients were in the ICU at infection onset. The common sources were respiratory tract (60.8%), osteoarticular (11.8%) and skin and soft tissue (11.8%). Two patients had positive blood cultures. PA antibiotic susceptibilities were as follows: ceftazidime 52.6% (n = 51), CZA 92.0% (n = 25), ciprofloxacin 10% (n = 30), meropenem 19.6% (n = 46), piperacillin–tazobactam 30.4% (n = 4) and tobramycin 72.9% (n = 48). Most (60.8%) infections were polymicrobial including 15 (29.4) CRE co-infections. CZA was started 97 (50, 170) hours after culture collection and continued for 9 (7, 14) days. Only 8 patients (15.7%) received active antibiotic therapy before CZA. Combination CZA therapy was used 35.3%, most often an aminoglycoside (8/18, 44.4%). Clinical cure or improvement was achieved in 40 patients (78.4%), and 42 (82.4%) were discharged alive. Among patients with repeat cultures (n = 11), CZA resistance development was not detected. Three patients (5.9%) experienced infection recurrence within 30 days of completing therapy. Conclusion The use of CZA was associated with high rates of favorable outcomes in complex patients with MDR PA infections. Future studies evaluating long-term outcomes and comparative studies are needed to more precisely define the role of CZA for MDR PA infections. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background We conducted this study to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam (CZA) for a range of multidrug-resistant Gram-negative (MDR-GN) infections. Methods This is a multicenter, retrospective cohort study conducted at 6 medical centers in the United States between 2015 and 2019. Adult patients who received CZA (≥72 hours) were eligible. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of infection on CZA. Results In total, data from 203 patients were evaluated. Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas spp were isolated from 117 (57.6%) and 63 (31.0%) culture specimens, respectively. The most common infection sources were respiratory (37.4%), urinary (19.7%), and intra-abdominal (18.7%). Blood cultures were positive in 22 (10.8%) patients. Clinical failure, 30-day mortality, and 30-day recurrence occurred in 59 (29.1%), 35 (17.2%), and 12 (5.9%) patients, respectively. On therapy, CZA resistance developed in 1 of 62 patients with repeat testing. Primary bacteremia or respiratory tract infection and higher SOFA score were positively associated with clinical failure (adjusted odds ratio [aOR] = 2.270, 95% confidence interval [CI] = 1.115–4.620 and aOR = 1.234, 95% CI = 1.118–1.362, respectively). Receipt of CZA within 48 hours of infection onset was protective (aOR, 0.409; 95% CI, 0.180–0.930). Seventeen (8.4%) patients experienced a potential drug-related adverse effect (10 acute kidney injury, 3 Clostridioides difficile infection, 2 rash, and 1 each gastrointestinal intolerance and neutropenia) Conclusions Ceftazidime-avibactam is being used to treat a range of MDR-GN infections including Pseudomonas spp as well as CRE. [ABSTRACT FROM AUTHOR]

Background Combination β-lactam and vancomycin (VAN) prevent the emergence of resistance and result in synergistic antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. We sought to provide clinical translation to these data and determine if patients with MRSA bloodstream infection (BSI) treated with VAN + cefazolin (VAN/CFZ) via our MRSA BSI clinical pathway had improved clinical outcomes compared VAN alone. Methods Multicenter, retrospective, comparative cohort study from 2006 to 2019 in adults with MRSA BSI treated with VAN for ≥ 72 hours. VAN/CFZ was defined as VAN + CFZ within ≤ 72 hours of index culture for ≥ 24 hours. Other β-lactams were allowed for < 48 h in the VAN/CFZ group. The VAN alone group could not have other β-lactams within 7 days of treatment initiation. The primary outcome was clinical failure defined as a composite of 30-d all-cause mortality, 60-day recurrence, and persistent BSI (≥ 7 days). The independent effect of VAN/CFZ on clinical failure was evaluated with multivariable logistic regression. The primary safety endpoint was nephrotoxicity within 7 days of treatment initiation. Results A total of 237 patients were included (104 VAN/CFZ, 133 VAN). The most common BSI sources were skin/soft tissue (29.1%), IV catheter (21.9%), osteoarticular (20.3%) and infective endocarditis (16.0%). Demographic and clinical characteristics were similar between groups except VAN/CFZ had a higher median APACHE II score (18 vs. 13, P = 0.011). VAN/CFZ patients were also more likely to have received an infectious disease consult (100% vs. 81.2%, P < 0.001). Median (IQR) duration of CFZ was 115 (87–164) hours. After controlling for age, APACHE II score, ID consult and infection source, VAN/CFZ was associated with reduced odds of clinical failure (aOR 0.425, 95% CI 0.228, 0.792). Bivariate outcomes are shown in the table: Conclusion Patients with MRSA BSI treated with VAN/CFZ vs. VAN experienced fewer clinical failures, supporting additional studies evaluating the role of adjuvant CFZ for MRSA BSI. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Data suggest that vancomycin + β-lactam combinations improve the clearance of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs). However, it is unclear which specific β-lactams confer benefit. This analysis evaluates the impact of concomitant empiric cefepime on outcomes of MRSA BSIs treated with vancomycin. Methods This was a multicenter, retrospective cohort study of adults with MRSA BSIs from 2006 to 2017. Vancomycin + cefepime therapy was defined as ≥24 hours of cefepime during the first 72 hours of vancomycin. The primary outcome was microbiologic failure, defined as BSI duration ≥7 days and/or 60-day recurrence. Multivariable logistic regression was used to evaluate the association between vancomycin + cefepime therapy and binary outcomes. Cause-specific and subdistribution hazard models were used to evaluate the association between vancomycin + cefepime and BSI clearance. Results Three hundred fifty-eight patients were included, 129 vancomycin and 229 vancomycin + cefepime. Vancomycin + cefepime therapy was independently associated with reduced microbiologic failure (adjusted odds ratio [aOR], 0.488; 95% confidence interval [CI], 0.271–0.741). This was driven by a reduction in BSI duration ≥7 days (vancomycin + cefepime aOR, 0.354; 95% CI, 0.202–0.621). Vancomycin + cefepime had no association with 30-day mortality (aOR, 0.952; 95% CI, 0.435–2.425). Vancomycin + cefepime was associated with faster BSI clearance in both cause-specific (hazard ratio [HR], 1.408; 95% CI, 1.125–1.762) and subdistribution hazard models (HR, 1.264; 95% CI, 1.040–1.536). Conclusions Concomitant empiric cefepime improved MRSA BSI clearance and may be useful as the β-lactam component of synergistic vancomycin + β-lactam regimens when empiric or directed gram-negative coverage is desired. [ABSTRACT FROM AUTHOR]

Background: Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin., Methods: Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied., Results: Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, -5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001)., Conclusions: No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Our objective was to describe the prescribing practices, clinical characteristics, and outcomes of patients treated with ceftolozane-tazobactam (C/T) for multidrug-resistant (MDR) Gram-negative infections. This was a multicenter, retrospective, cohort study at eight U.S. medical centers (2015 to 2019). Inclusion criteria were age ≥18 years and receipt of C/T (≥72 hours) for suspected or confirmed MDR Gram-negative infection. The primary efficacy outcome, evaluated among patients with MDR Pseudomonas aeruginosa infections, was composite clinical failure, namely, 30-day all-cause mortality, 30-day recurrence, and/or failure to resolve or improve infection signs or symptoms after C/T treatment. In total, 259 patients were included, and P. aeruginosa was isolated in 236 (91.1%). The MDR and extremely drug-resistant phenotypes were detected in 95.8% and 37.7% of P. aeruginosa isolates, respectively. The most common infection source was the respiratory tract (62.9%). High-dose C/T was used in 71.2% of patients with a respiratory tract infection (RTI) overall but in only 39.6% of patients with an RTI who required C/T renal dose adjustment. In the primary efficacy population ( n  = 226), clinical failure and 30-day mortality occurred in 85 (37.6%) and 39 (17.3%) patients, respectively. New C/T MDR P. aeruginosa resistance was detected in 3 of 31 patients (9.7%) with follow-up cultures. Hospital-acquired infection and Acute Physiological and Chronic Health Evaluation II (APACHE II) score were independently associated with clinical failure (adjusted odds ratio [aOR], 2.472 and 95% confidence interval [CI], 1.322 to 4.625; and aOR, 1.068 and 95% CI, 1.031 to 1.106, respectively). Twenty-five (9.7%) patients experienced ≥1 adverse effect (9 acute kidney injury, 13 Clostridioides difficile infection, 1 hepatotoxicity, 2 encephalopathy, and 2 gastrointestinal intolerance). C/T addresses an unmet medical need in patients with MDR Gram-negative infections., (Copyright © 2020 American Society for Microbiology.)