14 research outputs found
Regulatory Oversight and Safety of Probiotic Use
Saccharomyces boulardii probiotics should be used with caution for management of Clostridium difficile infections in hospitalized patients
Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections
Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV
Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas Aeruginosa
Background: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE).
Methods: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR).
Results: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941).
Conclusions: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs
Selecting Anti-infective Agents for the Treatment of Bone Infections: New Anti-infective Agents and Chronic Suppressive Therapy
Administration of a Survey to Evaluate the Attitudes of House Staff Physicians towards Antimicrobial Resistance and the Antimicrobial Stewardship Programme at a Community Teaching Hospital
Training a Drug to Do New Tricks: Insights on Stability of Meropenem Administered as a Continuous Infusion
Background: The antibiotic armamentarium used to combat multi-drug resistant organisms (MDROs) include carbapenems. Continuous infusion (CI) dosing is frequently employed to maximize beta-lactam efficacy; however, use of meropenem CI has been limited due to concerns with product instability. Objective: The primary objective of this study was to quantify meropenem serum concentrations to reflect drug stability when administered as CI over 8- or 12-h exchanges. In addition, a stability experiment was performed to further establish meropenem integrity over 12 h. The secondary objectives were to assess the ability of meropenem to achieve target pharmacokinetic/pharmacodynamic (PK/PD) exposures relative to the minimum inhibitory concentration (MIC) of the pathogen, and to determine clinical cure. Methods: This was a retrospective, observational study on use of CI meropenem (infused either over 8- or 12- h) at a 1% concentration. The stability experiment was conducted on 1% meropenem at room temperature. Results: In 22 patients, a median meropenem daily dose of 6 g/day (range 2-6 g/day) resulted in a median serum concentration of 17.8 mg/L (interquartile range, 9.3-27.8 mg/L). In 95% of cases, meropenem delivered as CI resulted in free drug concentrations at or above the MIC of the pathogen for the entire dosing interval. Clinical cure was achieved in 80% of patients included in this review. The stability experiment revealed negligible drug degradation at the end of the 12-h dosing interval. Conclusions: The data from this study provides compelling evidence for the use of meropenem as CI utilizing either a 12- or 8-h exchange process
Trimethoprim-sulfamethoxazole exposure alters exvivo functionofblymphocytes isolated from human immunodeficiency virus-infected patients receiving zidovudine
Association of piperacillin and vancomycin exposure on acute kidney injury during combination therapy
OBJECTIVES: Acute kidney injury (AKI) is a well-documented adverse effect observed with piperacillin/tazobactam in combination with vancomycin. The pharmacokinetics of these antibiotics when given in combination have not been previously evaluated. The purpose of this study was to compare the exposure of vancomycin + piperacillin/tazobactam in patients with and without AKI.METHODS: Ninety adult patients, who received at least 72 h of vancomycin + piperacillin/tazobactam combination therapy and had available serum concentrations of vancomycin and piperacillin were included in the study. Nephrotoxicity was defined as a 1.5-fold increase in serum creatinine within 7 days from baseline. Median daily AUCs were calculated in those with nephrotoxicity (vancomycin + piperacillin/tazobactam 'N') versus those without nephrotoxicity (vancomycin + piperacillin/tazobactam 'WN') during the first 7 days of combination therapy.RESULTS: The overall incidence of AKI in those receiving vancomycin + piperacillin/tazobactam was 20% (18/90). The median daily vancomycin AUCs did not differ between the vancomycin + piperacillin/tazobactam 'WN' and vancomycin + piperacillin/tazobactam 'N' groups. Although not statistically significant, the median daily vancomycin AUCs in the vancomycin + piperacillin/tazobactam 'N' group were numerically greater on Day 5 and trended downwards thereafter. For the piperacillin group, the median daily AUCs did not vary between groups, except on Day 7 where the vancomycin + piperacillin/tazobactam 'WN' group had statistically greater median piperacillin AUC than the vancomycin + piperacillin/tazobactam 'N' group ( P = 0.046). CONCLUSIONS: Utilizing serum creatinine-defined AKI, our study did not find any significant differences in vancomycin and piperacillin/tazobactam exposure between the groups with and without nephrotoxicity. These data indicate that vancomycin + piperacillin/tazobactam should not be avoided due to the risk of overexposure; instead, clinicians should continue to use these therapies cautiously.</p
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1575. Predictors of Negative Clinical Outcomes among Patients treated with Meropenem-Vaborbactam for Serious Gram-Negative Bacterial Infections: Impact of Delayed Appropriate Antibiotic Selection
Abstract
Background
Numerous number of studies have found a positive correlation between delayed appropriate antibiotic therapy and negative clinical outcomes (NCO) in Gram-negative bacterial infections (GNBI). The combination of meropenem with vaborbactam (MVB) received Food and Drug Administration approval for the treatment of complicated urinary tract infections and acute pyelonephritis caused by susceptible organisms in August 2017. We sought to determine the impact of delayed appropriate therapy with MVB on NCO among patients with GNBI.
Methods
Multi-center, retrospective cohort study from October 2017 to March 2020. We included adult patients treated with MVB for >72 hours. We excluded patients who received alternative appropriate antibiotics for GNB prior to MVB and patients with unknown dates for index culture. NCO were defined as 30-day mortality and/or microbiological recurrence. All outcomes were measured from MVB start date. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineates the risk of NCO. Multivariable logistic regression analysis (MLR) was used to examine the independent association between the CART-derived-BP and NCO. Variables were retained in the model if P< 0.2 and removed in a backward stepwise approach.
Results
A total of 86 patients were included from 13 institutions in the United States: median(IQR) age 55 (37-67) years, 67% male, and 48% Caucasian. Median(IQR) APACHE II and Charlson Comorbidity index scores were 18(11-26) and 4(2-6), respectively. Common sources of infection were respiratory (37%) and intra-abdominal (21%). The most common pathogens were carbapenem-resistant Enterobacterales (83%). CART-derived BP between early and delayed treatment was 48 hours, where NCO was increased (36% vs.7%; P=0.04). Delayed MVB initiation was independently associated with NCO in the MLR (aOR=7.4, P=0.02).
Results of Regression Analysis of Variables Associated With Negative Clinical Outcomes and Delayed Appropriate Therapy with Meropenem-vaborbactam
Conclusion
Our results suggest that delaying appropriate antibiotic therapy with MVB for >48 hours significantly increases the risk of NCO in patients with GNBI. Clinicians must ensure timely administration of MVB to assure best outcomes in patients with GNBI.
Disclosures
Kevin W. Garey, PharMD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support