Microbiological Eradication Rate Research Articles

Ceftazidime-avibactam combination therapy versus monotherapy for treating carbapenem-resistant gram-negative infection: a systemic review and meta-analysis.

This meta-analysis was conducted to compare the efficacy of ceftazidime-avibactam combination therapy with that of monotherapy in the treatment of carbapenem-resistant Gram-negative bacterial (CR-GNB). A literature search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was conducted until September 1, 2023. Only studies that compared CZA combination therapy with monotherapy for CR-GNB infections were included. A total of 25 studies (23 retrospective observational studies and 2 prospective studies) involving 2676 patients were included. There was no significant difference in 30-day mortality between the study group receiving combination therapy and the control group receiving monotherapy (risk ratio [RR] 0.91; 95% confidence interval [CI] 0.71-1.18). In addition, no significant differences were observed between the study and the control group in terms of in-hospital mortality (RR 1.00; 95% CI 0.79-1.27), 14-day mortality (RR 1.54; 95% CI 0.24-9.91), 90-day mortality (RR 1.18; 95% CI 0.62-2.22), and clinical cure rate (RR 0.95; 95% CI 0.84-1.08). However, the combination group had a borderline higher microbiological eradication rate than the control group (RR 1.15; 95% CI 1.00-1.32). Compared to monotherapy, CZA combination therapy did not yield additional clinical benefits. However, combination therapy may be associated with favorable microbiological outcomes.

Efficacy and safety of generic cefoperazone/sulbactam versus branded cefoperazone/sulbactam in the treatment of bacterial infections: a systematic review and meta-analysis

This study aim to assess the clinical efficacy and safety of generic cefoperazone/sulbactam compared to the branded cefoperazone/sulbactam (Sulperazon) in treating bacterial infections through a meta-analysis. Searches were conducted across PubMed, Embase, Cochrane Library, CNKI, WanFang, VIP databases, and Clinical Trials database, resulting in the inclusion of 11 studies comprising 7 randomized controlled trials (RCTs) and 4 retrospective cohort studies (RCSs). Meta-analysis of the RCTs indicated no statistical differences in clinical success rates, clinical cure rates, microbiological eradication rates, and incidence of adverse reactions between the generic cefoperazone/sulbactam and the branded version. Findings from the RCSs aligned with those from the RCTs, demonstrating that generic versions of cefoperazone/sulbactam are equivalent in efficacy and safety to their branded counterparts in treating bacterial infections.

Clinical Value Of Intravenous Fosfomycin Combinations

Aims:Due to the increasing number of Multi-Drug Resistance (MDR) and Extensively Drug Resistant (XDR) pathogens and the difficulties in developing new antibiotics, some combinations are being tried. Fosfomycin is a phosphonic acid derivative UDP-N-acetyl glucosamine (MurA) inhibitor. Fosfomycin inhibits bacteria cell wall synthesis in its first step. It acts against both gram-positive and gram-negative Multi-Drug Resistance (MDR) and Extensive Drug-Resistant (XDR) bacteria. It prevents bacterial invasion into the urinary system and respiratory tract epithelİum. It was aimed to evaluate the clinical and microbiological response rates of intravenous fosfomycin treatment in gram-negative MDR and XDR bacterial infections in this study.
 Methods: Total 77 patients from four different centers where used intravenous fosfomycin treatment were involved to the study. It was evaluated clinical and microbiological response in 72 hours after the beginning of treatment and at the end of treatment. Clinical and microbiological response have been evaluated in the study population. 
 Results: While 41 of the patients were female (53.2%), 36 were male (46.8%), it is found that their mean age was 60.5. Clinical response rates 72 hours after the initiation of treatment and at the end of treatment were 46 (59.7%) and 45 (58.4%), respectively. Microbiological eradication rate was achieved in 40 (51.9%) patients in the first 72 hours and in 39 (50.6%) patients at the end of the treatment. Clinical response and microbiological eradication rates after seventy two hours and at the end of treatment were found to be similar with together. 
 Conclusions: As a result, fosfomycin may be an alternative in combination therapy due to its low side effect profile and lack of drug interaction in the treatment of MDR and XDR pathogens.

Subgroup analysis of phase 2 study of ceftolozane/tazobactam in neonates and young infants with pyelonephritis.

Ceftolozane/tazobactam is approved for the treatment of patients from birth to <18 y old with complicated urinary tract infections (cUTI). This post hoc analysis evaluated the safety, efficacy, and pharmacokinetics (PK) of ceftolozane/tazobactam compared with meropenem in neonates and young infants. NCT03230838 was a phase 2, randomized, active comparator-controlled, double-blind study of patients from birth to <18 y of age with cUTI, including pyelonephritis, given ceftolozane/tazobactam or meropenem in a 3:1 ratio. This subset analysis included only neonates and young infants < 3 mo of age. The microbiologic modified intent-to-treat population (mMITT) included 20 patients (ceftolozane/tazobactam, n = 14; meropenem, n = 6). All patients had pyelonephritis at baseline; two patients in each treatment group had bacteremia (overall 4/20, 20%). Escherichia coli was the most common baseline pathogen (overall 16/20, 80%). Safety and efficacy results were similar between treatment groups and consistent with the overall pediatric population. There were no serious drug-related adverse events (AEs), no discontinuations due to AEs, and no AEs leading to death in either treatment group. For the ceftolozane/tazobactam and meropenem treatment groups, clinical cure rates in the mMITT population were 92.9% and 100%, respectively. The population PK analysis of neonates and young infants demonstrated similar ceftolozane and tazobactam exposures to those of adults, achieving pharmacodynamic targets associated with clinical and microbiologic cure. Ceftolozane/tazobactam has a favorable safety profile and achieves high clinical cure and microbiologic eradication rates in neonates and young infants < 3 mo of age with cUTI and pyelonephritis. IMPORTANCE Extrapolation of antibacterial agent pharmacokinetics from adults to newborns and young infants may not be appropriate; similarly, the clinical manifestations of infectious diseases and outcomes following antibacterial treatment may not be similar. Ceftolozane/tazobactam is an antibacterial drug combination active against Pseudomonas aeruginosa and other multidrug-resistant gram-negative bacteria. A clinical study led to the approval for ceftolozane/tazobactam in patients from birth to 18 y of age who have complicated urinary tract infections, including those with serious kidney infections. Based on data collected during that clinical study, we compared newborns and young infants who were treated with ceftolozane/tazobactam (14 patients) and those who were treated with meropenem (6 patients). We found that ceftolozane/tazobactam treatment of newborns and young infants up to 3 mo of age who have complicated urinary tract infections demonstrated a favorable safety profile and high clinical cure and microbiologic eradication rates, similar to meropenem.

Efficacy and Safety of Different Antibiotic Therapies for Bone and Joint Infections: A Network Meta-analysis of Randomized Controlled Trials.

Although an increasing number of antibiotics are being used to treat bone and joint infections, their specific efficacy remains controversial. Thus, we aimed to systematically compare the efficacy and safety of antibiotic therapies for orthopedic infections. PubMed, Embase, The Cochrane Library, and Web of Science databases were searched from inception to April 2022. Two authors independently and rigorously conducted the screening, data extraction, and quality assessment of the relevant studies. All the extracted data were evaluated using traditional metaanalysis and network meta-analysis by STATA SE 16.0. A total of eleven randomized controlled trials (RCTs) involving 1,063 patients were included for data analysis. The analysis results from the NMA indicated that in terms of the clinical effectiveness rate, linezolid (OR: 1.75, 95% CI: 1.01 to 3.02) showed significant efficacy compared to ampicillin/sulbactam. With regard to the microbiological eradication rate, linezolid showed significant efficacy compared to cephalosporins (OR: 8.13, 95% CI: 1.16 to 57.09) and quinolones (OR: 3.51, 95% CI: 1.18 to 10.49). Similar findings were obtained for subgroup populations with diabetic foot infections (DFI). However, linezolid was significantly related to higher adverse events than ampicillin/sulbactam (OR: 3.25, 95% CI: 1.68 to 6.30) and cephalosporins (OR: 18.29, 95% CI: 1.59 to 209.76). Linezolid appeared to be the most promising treatment regimen for staphylococcal bone and joint infections. However, due to the overall limited evidence, the research results need further high-quality RCTs for confirmation.

Relationship Between Real-time TDM-guided Pharmacodynamic Target Attainment of Continuous Infusion Beta-lactam Monotherapy and Microbiologic Outcome in the Treatment of Critically Ill Children With Severe Documented Gram-negative Infections.

To explore the relationship between real-time therapeutic drug monitoring (TDM)-guided pharmacodynamic target attainment of continuous infusion (CI) beta-lactam monotherapy and microbiological outcome in the treatment of critically ill children with severe documented Gram-negative infections. Observational, monocentric, retrospective study of critically ill patients receiving CI piperacillin-tazobactam, ceftazidime, or meropenem in monotherapy for documented Gram-negative infections optimized by means of a real-time TDM-guided strategy. Average steady-state beta-lactam concentrations (Css) were calculated for each patient, and the beta-lactam Css/minimum inhibitory concentration (MIC) ratio was selected as a pharmacodynamic parameter of efficacy. The Css/MIC ratio was defined as optimal if ≥4, quasi-optimal if between 1 and 4, and suboptimal if <1. The relationship between Css/MIC and microbiological outcome was assessed. Forty-six TDM assessments were carried out in 21 patients [median age 2 (interquartile range: 1-8) years]. Css/MIC ratios were optimal in 76.2% of cases. Patients with optimal Css/MIC ratios had both a significantly higher microbiological eradication rate (75.0% vs. 0.0%; P = 0.006) and lower resistance development rate (25.0% vs. 80.0%; P = 0.047) than those with quasi-optimal or suboptimal Css/MIC ratios. Quasi-optimal/suboptimal Css/MIC ratio occurred more frequently when patients had infections caused by pathogens with MIC values above the European Committee on Antimicrobial Susceptibility Testing clinical breakpoint (100.0% vs. 6.3%; P < 0.001). Real-time TDM-guided pharmacodynamic target attainment of CI beta-lactam monotherapy allowed to maximize treatment efficacy in most critically ill children with severe Gram-negative infections. Attaining early optimal Css/MIC ratios of CI beta-lactams could be a key determinant associated with microbiological eradication during the treatment of Gram-negative infections. Larger prospective studies are warranted for confirming our findings.

Tigecycline-Containing Regimens and Multi Drug-Resistant Acinetobacter baumannii: A Systematic Review and Meta-Analysis.

Introduction: The use of tigecycline (TG) for the treatment of Acinetobacter baumannii is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of TG for the treatment of multi drug-resistant (MDR) Acinetobacter. Methods: We searched PubMed/MEDLINE, Scopus, Cochrane Central, and Web of Science to identify studies reporting the clinical and microbiological efficacy and safety of regimens containing TG in patients with drug susceptibility testing (DST)-confirmed MDR A. baumannii, published until December 30, 2022. Observational studies were included if they reported clinical and microbiological efficacy of TG-based regimens. The Newcastle-Ottawa Scale (NOS) and Joana Briggs Institute (JBI) critical appraisal tool were used to assess the quality of included studies. Results: There were 30 observational studies, of which 19 studies were cohort and 11 studies were single group studies. Pooled clinical response and failure rates in the TG-containing regimens group were 58.1 (95% confidence interval [CI] 49.2-66.6) and 40.2 (95% CI 31.1-50.0), respectively. The pooled microbiological response rate was 32.1 (95% CI 19.8-47.5), and the pooled all-cause mortality rate was 41.1 (95% CI 34.1-48.4). Pooled clinical response and failure rates in the colistin-based regimens group were 52.7 (42.7-62.5) and 43.1 (33.1-53.8), respectively. The pooled microbiological response rate was 42.9 (16.2-74.5), and the pooled all-cause mortality rate was 34.3 (26.1-43.5). Conclusions: According to our results, the efficacy of the TG-based regimen is the same as other antibiotics. However, our study showed a high mortality rate and a lower rate of microbiological eradication for TG compared with colistin-based regimen. Therefore, our study does not recommend it for the treatment of MDR A. baumannii. However, this was a prevalence meta-analysis of observational studies, and for better conclusion experimental studies are required.

Efficacy and safety of ceftazidime–avibactam versus polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infection: a systematic review and meta-analysis

ObjectivesCarbapenem-resistant Enterobacteriaceae is increasingly recognised as a significant public health concern. Ceftazidime-avibactam (CAZ-AVI) and polymyxins are considered as the last therapeutic options worldwide. This is the first meta-analysis of recently...

Omadacycline for treatment of acute bacterial infections: a meta-analysis of phase II/III trials

ObjectiveThis study aims to assess the clinical efficacy and safety of omadacycline for the treatment of acute bacterial infections.MethodsA search of PubMed, Embase, Cochrane Library, and Clinical Trials was conducted up to July 1, 2022. We included only randomized controlled trials (RCTs), in which omadacycline and other antibiotics were evaluated for treating acute bacterial infections in adults. The primary outcomes were clinical response and microbiological response, whereas the secondary outcome was the risk of adverse events (AEs).ResultsA total of seven RCTs involving 2841 patients with acute bacterial infection were included. Overall, our study illustrated that the clinical cure ratio of omadacycline was similar to the comparators in the treatment of acute bacterial infections (OR = 1.18, 95%CI = 0.96, 1.46, I2 = 29%). Omadacycline had a microbiological eradication rate similar to comparators in the treatment of acute bacterial infections (OR = 1.02, 95%CI = 0.81, 1.29, I2 = 42%). No statistical differences were observed between omadacycline and the comparators in terms of infection caused by Staphylococcus aureus (OR = 1.14, 95%CI = 0.80, 1.63, I2 = 0%), methicillin-resistant S. aureus (MRSA, OR = 1.28, 95%CI = 0.73, 2.24, I2 = 0%), methicillin-susceptible S. aureus (MSSA, OR = 1.12, 95%CI = 0.69, 1.81, I2 = 0%), and Enterococcus faecalis (OR = 2.47, 95%CI = 0.36, 16.97, I2 = 7%). A significant difference was found between omadacycline and the comparators for the risk of any AEs and treatment related AEs. The risk of discontinuation of the study drug due to an AEs was lower for omadacycline than for the comparators.ConclusionOmadacycline is as good as comparators in terms of efficacy and tolerance in the treatment of acute bacterial infections in adult patients. Thus, omadacycline is an appropriate option for antibiotic therapy in adult patients with acute bacterial infections.

Clinical and cost-effectiveness analysis of carbapenems versus ciprofloxacin in the treatment of urinary tract infections due to extended spectrum β-lactamase-producing Enterobacterales

Urinary tract infections (UTIs) are the most common infectious diseases in both hospital and community settings. The management of UTIs caused by extended spectrum β-lactamase-producing Enterobacterales (ESBL-PE) has become more complicated given the limited options of effective antibiotic agents besides the amplification of total healthcare costs. This was a retrospective cohort study conducted among hospitalized patients between January 2018 and March 2020. Adults diagnosed with UTI due to ESBL-PE with at least 2days of admission were included. Excluded were patients with concomitant infection, polymicrobial UTI, and pregnant women. The primary endpoints were clinical cure and incremental cost-effectiveness ratio (ICER). Clinical cure, hospitalization, and antibiotics costs were considered to evaluate ICER. The secondary endpoints included microbiological eradication, length of stay (LOS), and 30-day readmission. Of 102 patients, 89 received acarbapenem and 13 received ciprofloxacin. The patients had similar baseline characteristics, including history of hospitalization and UTI within 3months. No difference was observed in clinical cure rates (86.5% vs. 100%, P = 0.159), microbiological eradication (93.1% vs. 100%, P = 0.639), median LOS (6days in both groups, P = 0.773), and 30-day readmission rates (41.6% vs. 46.2%, P = 0.755). The ICER of carbapenem to ciprofloxacin was - 7,626.05, indicating that ciprofloxacin was more cost-effective compared with carbapenems. Ciprofloxacin had comparable cure rates with carbapenems, lower risk of 30-day readmission, and was more cost-effective for the treatment of UTI due to ESBL-PE. Therefore, it should be considered as a valuable option if ESBL-PE showed susceptibility to it.

LB2302. Ceftobiprole Compared to Daptomycin With or Without Optional Aztreonam for the Treatment of Complicated Staphylococcus aureus (SAB): Results of a Phase 3, Randomized, Double-Blind Trial (ERADICATE)

Abstract Background SAB is common, serious, and potentially lethal. Antibiotic options are limited, especially for MRSA. Ceftobiprole is an advanced-generation cephalosporin with bactericidal activity against Gram-positive (including MRSA) and Gram-negative pathogens, with efficacy and safety demonstrated in previous Phase 3 studies in acute bacterial skin infections and pneumonia. The present study evaluated ceftobiprole in patients with complicated SAB. Methods ERADICATE was a randomized (1:1), double-blind, multicenter, Phase 3, non-inferiority trial comparing ceftobiprole (BPR) vs daptomycin (DAP) ± optional aztreonam, for up to 42 days of treatment, in patients with complicated SAB (NCT03138733). The primary efficacy endpoint was overall clinical success 70 days post-randomization, adjudicated by a blinded independent Data Review Committee. Success required survival, no new SAB complications, symptom improvement, SAB clearance, and no receipt of other potentially effective antibiotics. The non-inferiority margin for the difference in success rates was -15% (BPR-DAP, 95% CI, 2-sided, lower bound). Safety was assessed through adverse events (AE) and laboratory data. Results Of 390 patients randomized, 387 (189 BPR, 198 DAP) were in the modified intent-to-treat (mITT) population who received study medication and had a positive baseline blood culture for S. aureus (94 MRSA). Median treatment duration was 21 days for both groups. Key baseline characteristics were balanced (Fig. 1). In the BPR group 69.8% experienced success, compared to 68.7% for DAP (adjusted difference 2.0%, 95% CI -7.1% to 11.1%, Fig. 2). There were no significant differences in mortality, microbiological eradication, or in key subgroup analyses (Fig. 3). The proportion of patients experiencing ≥1 AE was 63% for BPR and 59% for DAP. Treatment-related severe or serious AEs were infrequent. Gastrointestinal AEs, mostly mild nausea, were more frequent with BPR, consistent with data from previous Phase 3 studies. Conclusion Ceftobiprole is non-inferior to daptomycin for overall success in patients with complicated SAB. All-cause mortality, microbiological eradication rates and new SAB complications were similar between treatment groups. Both treatments were well tolerated. Disclosures Thomas L. Holland, MD, Aridis: Advisor/Consultant|Basilea Pharmaceutica: Advisor/Consultant|Karius: Advisor/Consultant|Lysovant: Advisor/Consultant Sara E. Cosgrove, MD, Basilea: Advisor/Consultant|Debiopharma: Advisor/Consultant Sarah B. Doernberg, MD, MAS, Basilea: Advisor/Consultant|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Johnson and Johnson: Advisor/Consultant|NIH: Grant/Research Support|Regeneron: Grant/Research Support Maziar Assadi Gehr, MD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Marc Engelhardt, MD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Kamal Hamed, MD, Basilea Pharmaceutica: previous full time employee of Basilea Pharmaceutica International Ltd|Lysovant: full time employee of Lysovant Daniel Ionescu, MD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Mark Jones, PhD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Mikael Sauley, MSc, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Jennifer Smart, PhD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Harald Seifert, MD, Basilea Pharmaceutica: Advisor/Consultant|Debiopharm: Advisor/Consultant|Eumedica: Advisor/Consultant|Gilead: Advisor/Consultant|MSD: Advisor/Consultant|Shionogi: Advisor/Consultant Timothy C. Jenkins, MD, Basilea: Clinical outcomes adjudication committee Vance G. Fowler, Jr, MD, MHS, Armata Valanbio Akagera Aridis Roche: Advisor/Consultant|BASILEA: Grant/Research Support|Basilea Novartis Debiopharm Genentech: Advisor/Consultant|MedImmune Bayer Janssen Contrafect Regeneron Destiny Amphliphi Integrated Bioth: Advisor/Consultant|NIH MedImmune Allergan Theravance Novartis Merck Contrafect Karius Genentech Regeneron Janssen: Grant/Research Support.

677. Systematic Review of the Early Use Experince of Cefiderocol in Real World Practice

Abstract Background Gram-negative bacteria (GNB) with resistance to carbapenems is a growing global public health concern. The World Health Organisation have listed three priority GNB pathogens for the development of novel antimicrobial agents; Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales. The purpose of this systematic review (SR) was to report evidence on the use of cefiderocol (FDC), a siderophore cephalosporin, for patients with GNB infections in compassionate use or expanded access settings. Methods Searches were undertaken to identify relevant evidence up to December 2021. Two independent reviewers screened the records retrieved for relevance to the SR with disagreements adjudicated by a third reviewer. Patients receiving FDC in a compassionate use, expanded access setting or those with limited treatment options for the treatment of GNB infection were eligible. Eligible case reports and case series were assessed for quality using predefined tools and data were extracted (by a single reviewer with data checking performed by a second reviewer), tabulated and summarised. Results Forty-four studies (n=150 patients) were identified reporting the use of FDC; 3 case series studies and 41 case reports. The most commonly reported pathogens were P. aeruginosa (41.3%), A. baumannii (36.0%) and A. xylosoxidans (14.3%). The diagnoses varied widely across the included patients. All patients were administered FDC at a dose between 750 mg and 2 g per day on various schedules, adjusted for renal function for between one and six weeks. Clinical cure was reported in 137 patients using author-specified definitions with 74 patients (54.0%) reporting clinical cure and 18 (13.1%) reporting failure. Microbiological eradication was reported in 78 patients of whom 56 (71.8%) reported success, while 22 (28.2%) reported failure. For mortality (n=123) 80 patients (65.0%) remained alive at the end of treatment, while 43 (35.0%) died. Adverse event (AE) data was reported for 53 patients of whom 13 (24.5%) reported AEs, while 40 (75.5%) did not. See Table 1.0. Conclusion FDC is a promising therapy for patients with GNB infections with limited treatment options. Real world practice shows a high microbiological eradication rate and a small number of AEs. Disclosures Carlo Tascini, n/a, Shionogi: Grant/Research Support Aurelien Dinh, Professor of Infectious Disease, Shionogi: Advisor/Consultant|Shionogi: Board Member Christopher M. Longshaw, PhD, Shionogi: Employee Anita C. Fitzgerald, MPH, Shionogi: Shionogi commissioned York Health Economics Consortium of which I am an associate, to conduct the systematic review we are submitting to IDWeek Hannah Wood, BA MA, Shionogi: Shionogi commissioned York Health Economics Consortium of which I am an employee, to conduct the systematic review we are submitting to IDWeek Jacoby Vivien M. Patterson, MA Cantab, MB BChir, FFPH MD, Shionogi: Shionogi commissioned York Health Economics Consortium of which I am an associate, to conduct the systematic review we are submitting to IDW Deborah Watkins, MSc, Shionogi: Shionogi commissioned York Health Economics Consortium of which I am an employee, to conduct the systematic review we are submitting to IDWeek Katy Wilson, LLM, Shionogi: Shionogi commissioned York Health Economics Consortium of which I am an employee to conduct the systematic review we are submitting to IDWeek Karan Gill, Master of Science, Shionogi: Employee.

Efficacy and Safety of Plazomicin in the Treatment of Enterobacterales Infections: A Meta-analysis of Randomized Controlled Trials

BackgroundIn the present study, we aimed to compare the efficacy and safety of plazomicin with comparators for the treatment of Enterobacterales infections.MethodsRandomized controlled trials (RCTs) assessing plazomicin for Enterobacterales infections were searched on the PubMed, Embase, and Cochrane Library databases. Meta-analyses were used to evaluate the efficacy and safety in RCTs.ResultsA total of 3 RCTs consisting of 761 patients were included in the present analysis. The study population included complex urinary tract infections (cUTIs), bloodstream infections (BSIs), and hospital-acquired pneumonia (HAP). Plazomicin had a clinical remission rate in the modified intention-to-treat (MITT) population that was similar to that of comparators (odds ratio [OR], 1.02; 95% CI, 0.60–1.73; I2 = 45%) in the pooled analysis of the 3 studies. The overall microbiologic eradication rate in the microbiological MITT (mMITT) population was similar to that of the comparators group (OR, 1.46; 95% CI, 0.72–2.95; I2 = 0%). However, the microbiologic recurrence rate of plazomicin for Enterobacterales was lower than that in the comparators group (OR, 0.38; 95% CI, 0.17–0.86; P = .02; I2 = 0%). No significant differences were found between plazomicin and comparators for the risk of any adverse events (OR, 0.78; 95% CI, 0.55–1.11; I2 = 0%).ConclusionsPlazomicin is as good as comparators in terms of efficacy and tolerance in the treatment of Enterobacterales infections. Therefore, plazomicin is a suitable choice for antibiotic treatment in adult patients with cUTIs, BSIs, or HAP.

Ceftazidime/Avibactam-Based Versus PolymyxinB-Based Therapeutic Regimens for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection in Critically Ill Patients: A Retrospective Cohort Study.

Considering the importance of ceftazidime/avibactam (CAZ/AVI) and polymyxinB (PMB) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, it is essential to evaluate the efficacy and safety of these agents and provide appropriate medical advice to clinical specialists. We conducted a retrospective cohort study in two Chinese tertiary hospitals for critically ill patients with CRKP infection who received at least 24-h CAZ/AVI-based or PMB-based treatment. A binary logistic model and a Cox proportional hazards regression model were constructed to analyze variables that could potentially affect 30-day microbiological eradication and all-cause mortality, respectively. From January 2019 to December 2021, 164 eligible patients were divided into CAZ/AVI and PMB cohorts. A notably lower 30-day mortality rate (35.4% vs 69.5%, P < 0.001) and a higher 30-day microbiological eradication rate (80.5% vs 32.9%, P < 0.001) were observed for patients receiving CAZ/AVI-based treatment, compared with cases in the PMB group. A longer antimicrobial treatment duration (> 7days) could also significantly decrease the mortality rate and increase the microbiological eradication rate. Female patients had a higher survival rate than male patients. Age over 65years, sepsis, continuous renal replacement therapy, and organ transplantation were identified as negative factors for survival. In the subgroup analysis, CAZ/AVI combined with tigecycline or amikacin could effectively lower mortality. According to safety evaluation results, potential elevation of hepatic enzymes was associated with CAZ/AVI-based treatment, while renal impairment was probably related to PMB-based treatment. CAZ/AVI was more effective than PMB in treating CRKP-infected patients. Tigecycline and amikacin were proven to be beneficial as concomitant agents in combination with CAZ/AVI. A treatment period lasting over 7days was recommended. Hepatoxicity of CAZ/AVI and nephrotoxicity of PMB should be monitored carefully. Further well-designed studies should be performed to verify our conclusion.

The necessity of a loading dose when prescribing intravenous colistin in critically ill patients with CRGNB-associated pneumonia: a multi-center observational study

BackgroundThe importance or necessity of a loading dose when prescribing intravenous colistin has not been well established in clinical practice, and approximate one-third to half of patients with carbapenem-resistant gram-negative bacteria (CRGNB) infection did not receive the administration of a loading dose. The aim of this study is to investigate the efficacy and risk of acute kidney injury when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.MethodsThis was a multicenter, retrospective study that recruited ICU-admitted patients who had CRGNB-associated nosocomial pneumonia and were treated with intravenous colistin. Then, we classified the patients into colistin loading dose (N = 85) and nonloading dose groups (N = 127). After propensity-score matching for important covariates, we compared the mortality rate, clinical outcome and microbiological eradication rates between the groups (N = 67).ResultsThe loading group had higher percentages of patients with favorable clinical outcomes (55.2% and 35.8%, p = 0.037) and microbiological eradication rates (50% and 27.3%, p = 0.042) at day 14 than the nonloading group. The mortality rates at days 7, 14 and 28 and overall in-hospital mortality were not different between the two groups, but the Kaplan–Meier analysis showed that the loading group had a longer survival time than the nonloading group. Furthermore, the loading group had a shorter length of hospital stay than the nonloading group (52 and 60, p = 0.037). Regarding nephrotoxicity, there was no significant difference in the risk of developing acute kidney injury between the groups.ConclusionsThe administration of a loading dose is recommended when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.

Clinical and Microbiological Efficacy of CSE-1034 in Treatment of Acute Bacterial Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

This study aimed to conduct a meta-analysis to assess the clinical and microbiological efficacy of CSE-1034 for treating acute bacterial infections in adult patients. PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched from their inception until April 2022 for relevant randomized controlled trials (RCTs). Only RCTs evaluating CSE-1034 and comparators for treating acute bacterial infections in adult patients were included. The primary outcome was the clinical response rate at the end of treatment (EOT) evaluation. Five RCTs were included. A total of 950 patients (n:638 in the UTI group, n:186 in the lower respiratory tract infection group, n:70 in the bone and joint infection group, and n:56 in SSSI) were included in this meta-analysis; 478 and 472 patients received CSE-1034 and comparators, respectively. Overall, CSE-1034 had a higher clinical cure rate at EOT than did the comparators (95.3% [384/403] vs. 81% [319/394], RR, 1.2; 95%CI, 1.04-1.39; I2=92%). Moreover, the clinical failure rate of CSE-1034 was lower than that of the comparators (RR, 0.04; 95%CI, 0.01-0.13; I2=0%). CSE-1034 also had a higher microbiological eradication rate than the comparators (92.9% [315/339] vs. 71.1% [216/304], RR, 1.53; 95%CI, 1.06-2.21; I2=97%). The clinical and microbiological efficacy of CSE-1034 is comparable or even superior in treating acute bacterial infections.

1143. Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonatal and Pediatric Participants With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized, Clinical Trial

BackgroundCeftolozane/tazobactam (C/T) is a cephalosporin–β-lactamase inhibitor combination approved to treat complicated urinary tract infections (cUTI), complicated intra-abdominal infections, and nosocomial pneumonia in adults. Safety and efficacy of C/T in neonatal and pediatric participants with cUTI was assessed.MethodsThis phase 2, randomized, double-blind study (NCT03230838) compared C/T with meropenem (MEM) for treatment of cUTI, including pyelonephritis in participants from birth to 18 years of age. Treatment duration was 7-14 days. After 3 days of intravenous therapy, optional oral step-down therapy was allowed. Participants were stratified and dosed by age group (Table 1). The primary objective was to evaluate the safety and tolerability of C/T compared with MEM, and key secondary end points included clinical response and per-participant microbiologic response at end of treatment (EOT) and test of cure (TOC). ResultsParticipants were randomized 3:1 and treated with C/T (n=100) or MEM (n=33). The microbiologic modified intent-to-treat population (mMITT) included 95 participants in the C/T (n=71) and MEM (n=24) arms; the most common reason for mMITT exclusion was lack of a qualifying baseline uropathogen (28.4%). Pyelonephritis was the most common baseline diagnosis (83.2%), and Escherichia coli was the most common qualifying baseline uropathogen (77.9%). Overall mean treatment duration was comparable in both arms (C/T, 10.2 days; MEM, 10.7); a total of 50 (70.4%) and 20 (83.3%) participants switched to optional oral step-down therapy in the C/T and MEM arms, respectively, both for a mean of approximately 6 days. The overall incidence of adverse events (AE; all and drug related), serious AE (SAE), and AE leading to discontinuation was comparable between C/T and MEM arms. There were no AE leading to death, drug-related SAE, or discontinuations due to drug-related AE or SAE (Table 2). For C/T and MEM, rates of clinical cure and microbiologic eradication at EOT and TOC were high (Figure). ConclusionIn this study, C/T was well tolerated with a safety profile comparable to MEM and to the previously reported safety profile for C/T in adults with cUTI. C/T achieved high clinical cure and microbiologic eradication rates and is a potential new treatment option for children with cUTI.Disclosures Emmanuel Roilides, MD, PhD, FIDSA, FAAM, FESCMID, Merck Sharp & Dohme Corp. (Consultant, Grant/Research Support) Negar Ashouri, MD, Merck Sharp & Dohme Corp. (Grant/Research Support) Matthew G. Johnson, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Julia Lonchar, MSc, Merck Sharp & Dohme Corp. (Employee, Shareholder) Feng-Hsiu Su, MPH, MBA, Merck Sharp & Dohme Corp. (Employee, Shareholder) Jennifer A. Huntington, PharmD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Myra W. Popejoy, PharmD, Merck Sharp & Dohme Corp. (Employee) Mekki Bensaci, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Carisa S. De Anda, PharmD, Merck Sharp & Dohme Corp. (Employee, Shareholder) Elizabeth G. Rhee, MD, Merck Sharp & Dohme Corp (Employee, Shareholder) Christopher Bruno, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee)

Clinical Efficacy and Safety of Cefoperazone-Sulbactam in Treatment of Intra-Abdominal Infections: A Systematic Review and Meta-Analysis.

Background: In this systematic review and meta-analysis, we aimed to assess the clinical efficacy and safety of cefoperazone-sulbactam against alternative antibiotics in the treatment of intra-abdominal infections. Methods: The PubMed, Cochrane, Web of Science, Ovid Medline, and CKNI databases were searched for relevant articles up to November 25, 2020. The primary outcome was clinical efficacy rate, and the secondary outcomes were microbiologic eradication rate, mortality rate, and adverse event (AE) risk. Results: Twelve studies involving 1,674 patients were included. Overall, the clinical efficacy rate of cefoperazone-sulbactam and comparators was 87.7% and 81.7%, respectively, and cefoperazone-sulbactam was associated with a higher clinical efficacy rate than that the comparator (odds ratio [OR] 1.98; 95% confidence interval [CI] 1.31-3.00; I2 = 36%). Additionally, cefoperazone-sulbactam was associated with a lower clinical failure rate (OR 0.40; 95% CI 0.28-0.57; I2 = 0) and a higher clinical cure rate (OR 1.54; 95% CI 1.17-2.03; I2 = 0) than the comparators. Cefoperazone-sulbactam was associated with a higher microbiologic eradication rate than the comparator (OR 2.54; 95% CI 1.72-3.76; I2 = 0). Finally, there was no significant difference between cefoperazone-sulbactam and the comparators in terms of mortality rate (OR 090; 95% CI 0.38-2.16; I2 = 0) and AE risk (OR 1.07; 95% CI 0.74-1.55; I2 = 0). Conclusions: The clinical efficacy and safety of cefoperazone-sulbactam were similar to those of alternative antibiotics in the treatment of intra-abdominal infections. Therefore, cefoperazone-sulbactam could be recommended as an effective and safe antibiotic for treating intra-abdominal infections.

Meta-analysis of vancomycin versus linezolid in pneumonia with proven methicillin-resistant Staphylococcus aureus

ObjectiveAmerican Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines suggest that linezolid (LZD) is preferred over vancomycin (VCM) for treating methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. We conducted a systematic review and comparative meta-analysis to compare VCM and LZD efficacy against proven MRSA pneumonia. MethodsWe searched EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed up to November 2019. The outcomes of the meta-analysis were mortality, clinical cure, microbiological evaluation, and adverse events. ResultsSeven randomized controlled trials (RCTs) with a total of 1239 patients and eight retrospective cohort or case–control studies (CSs) with a total 6125 patients were identified. Clinical cure and microbiological eradication rates were significantly increased in patients treated with LZD in RCTs (clinical cure: risk ratio (RR) = 0.81, 95% confidential interval (CI) = 0.71–0.92; microbiological eradication: RR = 0.71, 95% CI = 0.62–0.81) and CSs (clinical cure: odds ratio (OR) = 0.35, 95% CI = 0.18–0.69). However, mortality was comparable between patients treated with VCM and LZD in RCTs (RR = 1.08, 95% CI = 0.88–1.32) and CSs (OR = 1.20, 95% CI = 0.94–1.53). Likewise, there was no significant difference in adverse events between VCM and LZD in CSs (thrombocytopenia: OR = 0.95, 95% CI = 0.50–1.82; nephrotoxicity: OR = 1.72, 95% CI = 0.85–3.45). ConclusionsAccording to our meta-analysis of RCTs and CSs conducted worldwide, we found robust evidence to corroborate the IDSA guidelines for the treatment of proven MRSA pneumonia.

1257. A phase II Prospective Randomized Study to Assess Ceftolozane-Tazobactam in the Management of Febrile Neutropenia in Patients with Hematological Malignancies

BackgroundDespite the implementation of successful antibiotic stewardship programs, antibiotic resistance continue to emerge particularly against gram-negative bacteria. With the increase use of antibiotics in high risk patients with hematological malignancies, the empiric therapy with standard antibiotic could be inappropriate. New antibiotics may be useful to cover potential resistant pathogens. We evaluated the role of a new cephalosporin /β-lactamase inhibitor ceftolozane-tazobactam (C/T) in comparison to standard of care (SOC) antibiotics in the empiric treatment of febrile neutropenic cancer patients with hematological malignancies.MethodsWe conducted a prospective randomized open label comparative study to evaluate the safety and efficacy of C/T vs SOC antibiotics consisting of cefepime, piperacillin-tazobactam or meropenem when used in combination with gram positive antibacterial agents. Between May 2018 and March 2020, we enrolled 88 febrile neutropenic patients with hematological malignancies who presented to our emergency center. Patients received at least 72 hours of intravenous study drugs and were followed through end of IV therapy and for up to 42 days.ResultsA total of 88 patients were analyzed of whom 42 received C/T and 46 SOC antimicrobial agents. The rate of documented bloodstream infections was similar in both groups (CE-TZ 21% vs SOC 26%, p=0.61). Favorable clinical response at end of IV therapy was significantly better in the C/T arm compared to SOC therapy (88% vs 72%, p=0.039), at test of cure (21 days), and last follow-up (42 days). In patients with documented infections, the rate of microbiological eradication was similar in both groups. Drug-related adverse events that led to drug discontinuation was similar in both groups (7%). Similarly overall mortality was similar in both groups.ConclusionThe empiric use of C/T to cover gram negative organisms in high risk febrile neutropenic patients with hematological malignancies is safe and associated with better clinical outcome than SOC antimicrobial agents. The emergence of resistant pathogens should be further evaluated.Disclosures Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)