Compliance with recommended pneumococcal vaccination schedule in patients treated for rheumatoid arthritis: A retrospective cohort study in the Veterans Affairs population.

INTRODUCTION: Invasive pneumococcal disease (IPD) is a leading cause of death. Rheumatoid arthritis (RA) patients are at risk of IPD due to immunosuppressant medications. Up until 2022, two pneumococcal vaccines, the 13-valent Pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23), were recommended. Despite the recommendation change to give a single 20-valent PCV vaccine (PCV20), some still require multiple vaccinations. There is a need to identify barriers to vaccine uptake. METHODS: We conducted a retrospective cohort study to assess the on-time vaccination rates for PCV13 and PPSV23 in treated RA patients between 2010 and 2018 using national Veterans Affairs data. Patients > 18 years of age diagnosed with RA and newly initiated on RA treatment were included. Pneumococcal vaccine compliance was assessed by measuring on-time receipt of PCV13 and PPSV23 vaccinations. We identified factors using multivariate logistic regression and described the occurrence of these factors using descriptive statistics. RESULTS: A total of 39,243 patients were included in the study. Most patients were white (75.8 %), male (85.4 %), on methotrexate therapy (41.4 %). The average age was 62.3 years. The proportion of patients considered vaccine compliant is 43.9 %. The primary independent risk factors for vaccine non-compliance were black/African American race (Odds Ratio [OR] 1.26, 95 % Confidence Interval [CI] 1.19-1.34) or missing/unknown race (OR 1.45, 95 % CI 1.31-1.61), missing/unknown ethnicity (OR 1.21, 1.02-1.43), never married (OR 1.10, 95 % CI 1.02-1.19) or widowed (OR 1.23, 95 % CI 1.12-1.34), diagnosed with congestive heart failure (OR 1.10, 95 % CI 1.00-1.22), or dementia (OR 1.48, 95 % CI 1.16-1.91). The proportion of patients who were non-compliant in patients who were vaccine naïve was 32.1 % and the non-compliance rate for non-naïve patients was 65.3 %. CONCLUSIONS: Providers should identify barriers to pneumococcal vaccination in RA patients to improve compliance. Efforts to increase vaccination should be tailored to specific high-risk groups.

Optimizing anidulafungin exposure across a wide adult body size range.

Echinocandins like anidulafungin are first-line therapies for candidemia and invasive candidiasis, but their dosing may be suboptimal in obese patients. Our objective was to quantify anidulafungin exposure in a cohort of adults across a wide body size range to test if body size affects anidulafungin pharmacokinetics (PK). We enrolled 20 adults between the ages of 18 and 80 years, with an equal distribution of patients above and below a body mass index of 30 kg/m2. A single 100-mg dose of anidulafungin was administered, followed by intensive sampling over 72 h. Population PK analysis was used to identify and compare covariates of anidulafungin PK parameters. Monte Carlo simulations were performed to compute the probability of target attainment (PTA) based on alternative dosing regimens. Participants (45% males) had a median (range) age of 45 (21-78) years and a median (range) weight of 82.7 (42.4-208.3) kg. The observed median (range) of AUC0-∞ was 106.4 (51.9, 138.4) mg∙h/L. Lean body weight (LBW) and adjusted body weight (AdjBW) were more influential than weight as covariates of anidulafungin PK parameters. The conventional 100 mg daily maintenance is predicted to have a PTA below 90% in adults with an LBW > 55 kg or an AdjBW > 75 kg. A daily maintenance dose of 150-200 mg is predicted in these heavier adults. Anidulafungin AUC0-∞ declines with increasing body size. A higher maintenance dose will increase the PTA compared to the current approach in obese patients.

Insufficient Representation of Patients With Obesity in Randomized Controlled Trials Evaluating the Efficacy and Safety of Antimicrobials for Treatment of Skin and Skin Structure Infections: A Scoping Review.

Persons with obesity (PwO) represent approximately 50% of acute bacterial skin and skin structure infections (ABSSSIs) in the United States (US). There are currently insufficient data in PwO for drugs used for ABSSSIs. We conducted a scoping review of randomized controlled trials (RCTs) published between 2000 and 2022 to describe how frequently body size measures were reported. Weight and/or body mass index (BMI) were recorded in approximately 50% of the 69 RCTs. The average weights or BMIs were lower than US averages for most RCTs reporting data. None evaluated the impact of body size on outcomes in the original publication. Only 30% of newly approved drugs mention PwO representation in the prescribing information. More representative recruitment of PwO into RCTs is needed to help clinicians evaluate efficacy in these patients. We suggest that the Food and Drug Administration require companies to submit plans to ensure adequate PwO inclusion and that authors of RCTs report subgroup results based on body size.

Controversies in the Prevention and Treatment of Clostridioides difficile Infection in Adults: A Narrative Review.

Clostridioides difficile remains a problematic pathogen resulting in significant morbidity and mortality, especially for high-risk groups that include immunocompromised patients. Both the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA), as well as the American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recently provided guideline updates for C. difficile infection (CDI). In this narrative review, the authors reviewed available literature regarding the prevention or treatment of CDI in adults and focused on disagreements between the IDSA/SHEA and ACG guidelines, as well as articles that have been published since the updates. Several options for primary prophylaxis are available, including probiotics and antibiotics (vancomycin, fidaxomicin). The literature supporting fidaxomicin is currently quite limited. While there are more studies evaluating probiotics and vancomycin, the optimal patient populations and regimens for their use have yet to be defined. While the IDSA/SHEA guidelines discourage metronidazole use for mild CDI episodes, evidence exists that it may remain a reasonable option for these patients. Fidaxomicin has an advantage over vancomycin in reducing recurrences, but its use is limited by cost. Despite this, recent studies suggest fidaxomicin's cost-effectiveness as a first-line therapy, though this is highly dependent on institutional contracts and payment structures. Secondary prophylaxis should focus on non-antimicrobial options to lessen the impact on the microbiome. The oral option of fecal microbiota transplantation (FMT), SER109, and the now FDA-approved RBX2660 represent exciting new options to correct dysbiosis. Bezlotoxumab is another attractive option to prevent recurrences. Further head-to-head studies of newer agents will be needed to guide selection of the optimal therapies for CDI primary and secondary prophylaxis.

How Well Are Pharmacists Represented in National Institutes of Health R01 Funding to United States Schools of Pharmacy?

Pharmacists are essential healthcare providers but historically are not well represented as principal investigators (PIs) of R01 grants by the United States (US) National Institutes of Health (NIH). Pharmacy organizations have taken steps to provide pharmacists with research training to improve their chances of achieving PI status. We conducted a retrospective cohort study using data from the NIH RePORTER website about R01 grants awarded to PIs affiliated with US Schools of Pharmacy (SOPs) for the fiscal years 2005−2019. Information regarding professional degrees was supplemented using data from the PIs' institutional website profiles and other internet-based sources. Only doctorate degrees obtained within the US were included for clinically related degrees. Data regarding more than one year of funding for the same project, equipment supplements, and diversity supplements were excluded to focus on unique projects in year one of funding. PhDs were the primary unique PIs of R01 grants at US SOPs (>90%). Pharmacist representation as unique PIs increased over the 15 years but was still only 10.1% for the years 2015−2019. There was a higher percentage of female pharmacists as unique PIs than female non-pharmacists. Pharmacists are currently underrepresented as unique PIs for NIH R01 grants. This conclusion is limited by not knowing how many pharmacist R01 applications were submitted.

The Risk and Clinical Implications of Antibiotic-Associated Acute Kidney Injury: A Review of the Clinical Data for Agents with Signals from the Food and Drug Administration's Adverse Event Reporting System (FAERS) Database.

Antibiotic-associated acute kidney injury (AA-AKI) is quite common, especially among hospitalized patients; however, little is known about risk factors or mechanisms of why AA-AKI occurs. In this review, the authors have reviewed all available literature prior to 1 June 2022, with a large number of AKI reports. Information regarding risk factors of AA-AKI, mechanisms behind AA-AKI, and treatment/management principles to decrease AA-AKI risk were collected and reviewed. Patients treated in the inpatient setting are at increased risk of AA-AKI due to common risk factors: hypovolemia, concomitant use of other nephrotoxic medications, and exacerbation of comorbid conditions. Clinicians should attempt to correct risk factors for AA-AKI, choose antibiotic therapies with decreased association of AA-AKI to protect their high-risk patients, and narrow, when clinically possible, the use of antibiotics which have decreased incidence of AKI. To treat AKI, it is still recommended to discontinue all offending nephrotoxic agents and to renally adjust all medications according to package insert recommendations to decrease patient harm.

Using the HyFlex model to deliver a capstone seminar course.

INTRODUCTION: The HyFlex course structure allows students to attend class in-person or via synchronous videoconferencing technology. This model has been described, but no data are available in pharmacy curricula. METHODS: Students enrolled in Grand Rounds (GR) were eligible. The GR Engagement Assessment Tool (GREAT) measured engagement three times during the semester. Eighteen statements across four domains were rated using a five-point Likert scale (1 = not true at all and 5 = completely true). Free-text responses were collected for qualitative analysis. The primary outcome was the difference in GR engagement between students attending in-person vs. remotely. Descriptive statistics were used for demographic information. Wilcoxon rank-sum tests compared Likert-scale responses between in-person and remote attendance. RESULTS: Surveys included 128 responses from 88 unique students. There were no differences between remote and in-person attendance for the boredom and elaboration domains. In-person students reported listening more intently (median 4, IQR [3,4]; P = .03). In-person students felt the material was more practical (median 4, IQR [4,5]) than remote students (median 4, IQR [3,4]; P = .002) and more applicable to other situations (median 3, IQR [3,5]) than remote students (median 3, IQR [2,4]; P = .04). Qualitative analysis of the entire cohort demonstrated five themes for satisfaction: safety, flexibility, convenience, technology, and professionalism. CONCLUSIONS: There were subtle differences in student engagement or satisfaction using the HyFlex model. This study supports the expansion of this methodology to similar courses where remote instruction is needed.

Effects of Propofol on Hemodynamic Profile in Adults Receiving Targeted Temperature Management.

Background: Propofol is a key component for the management of sedation and shivering during targeted temperature management (TTM) following cardiac arrest. The cardiac depressant effects of propofol have not been described during TTM and may be especially relevant given the stress to the myocardium following cardiac arrest. The purpose of this study is to describe hemodynamic changes associated with propofol administration during TTM. Methods: This single center, retrospective cohort study evaluated adult patients who received a propofol infusion for at least 30 minutes during TTM. The primary outcome was the change in cardiovascular Sequential Organ Failure Assessment (cvSOFA) score 30 minutes after propofol initiation. Secondary outcomes included change in systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), and vasopressor requirements (VR) expressed as norepinephrine equivalents at 30, 60, 120, 180, and 240 minutes after propofol initiation. A multivariate regression was performed to assess the influence of propofol and body temperature on MAP, while controlling for vasopressor dose and cardiac arrest hospital prognosis (CAHP) score. Results: The cohort included 40 patients with a median CAHP score of 197. The goal temperature of 33°C was achieved for all patients. The median cvSOFA score was 1 at baseline and 0.5 at 30 minutes, with a non-significant change after propofol initiation (P = .96). SBP and MAP reductions were the greatest at 60 minutes (17 and 8 mmHg; P < .05 for both). The median change in HR at 120 minutes was -9 beats/minute from baseline. This reduction was sustained through 240 minutes (P < .05). No change in VR were seen at any time point. In multivariate regression, body temperature was the only characteristic independently associated with changes in MAP (coefficient 4.95, 95% CI 1.6-8.3). Conclusion: Administration of propofol during TTM did not affect cvSOFA score. The reductions in SBP, MAP, and HR did not have a corresponding change in vasopressor requirements and are likely not clinically meaningful. Propofol appears to be a safe choice for sedation in patients receiving targeted temperature management after cardiac arrest.

The Risk of Clostridioides difficile Recurrence after Initial Treatment with Vancomycin or Fidaxomicin Utilizing Cerner Health Facts.

(1) Background: Fidaxomicin has been shown to significantly reduce Clostridioides difficile infection (CDI) recurrences rates in randomized, controlled trials. However, national data from the Veterans Affairs has called the real-world applicability of these findings into question. Therefore, we conducted a retrospective cohort study of patients receiving fidaxomicin or vancomycin as initial therapy for an index case of CDI in the hospital to evaluate the relative rates CDI recurrence within 90 days of an index case. (2) Methods: We retrieved patients 18 years and older who were admitted between July 2011 through June 2018 and diagnosed and treated for CDI with vancomycin or fidaxomicin. The first occurrence of CDI with treatment was designated as the index case. Patients with CDI within 1 year prior to index case were excluded. From the remaining index cases (vancomycin = 14,785; fidaxomicin = 889) the primary outcome (a recurrence of CDI within 90 days of the index case) was determined. The CDI recurrence rates for fidaxomicin and vancomyicn were evaluated using a Cox Proportional Hazards model on a propensity score matched cohort. (3) Results: A statistically significantly lower risk of CDI recurrence was observed with fidaxomicin use in the matched cohort (889 patients per treatment) using a Cox Proportional Hazards model (HR 0.67, 95% CI 0.50-0.90). (4) Conclusions: Fidaxomicin was independently associated with a decreased CDI recurrence, as defined by readmission for CDI within 90 days.

Preoperative imaging of glioblastoma patients using hyperpolarized 13C pyruvate: Potential role in clinical decision making.

BACKGROUND: Glioblastoma remains incurable despite treatment with surgery, radiation therapy, and cytotoxic chemotherapy, prompting the search for a metabolic pathway unique to glioblastoma cells.13C MR spectroscopic imaging with hyperpolarized pyruvate can demonstrate alterations in pyruvate metabolism in these tumors. METHODS: Three patients with diagnostic MRI suggestive of a glioblastoma were scanned at 3 T 1-2 days prior to tumor resection using a 13C/1H dual-frequency RF coil and a 13C/1H-integrated MR protocol, which consists of a series of 1H MR sequences (T2 FLAIR, arterial spin labeling and contrast-enhanced [CE] T1) and 13C spectroscopic imaging with hyperpolarized [1-13C]pyruvate. Dynamic spiral chemical shift imaging was used for 13C data acquisition. Surgical navigation was used to correlate the locations of tissue samples submitted for histology with the changes seen on the diagnostic MR scans and the 13C spectroscopic images. RESULTS: Each tumor was histologically confirmed to be a WHO grade IV glioblastoma with isocitrate dehydrogenase wild type. Total hyperpolarized 13C signals detected near the tumor mass reflected altered tissue perfusion near the tumor. For each tumor, a hyperintense [1-13C]lactate signal was detected both within CE and T2-FLAIR regions on the 1H diagnostic images (P = .008). [13C]bicarbonate signal was maintained or decreased in the lesion but the observation was not significant (P = .3). CONCLUSIONS: Prior to surgical resection, 13C MR spectroscopic imaging with hyperpolarized pyruvate reveals increased lactate production in regions of histologically confirmed glioblastoma.

Efficacy and benefits of mock residency interviews.

INTRODUCTION: Obtaining a residency has become more competitive as more pharmacy students seek postgraduate training. This is likely due to pharmacist positions increasing in clinical settings. To be fully prepared, students seeking residency positions should be trained for the interview process by their pharmacy school. METHODS: Mock residency interviews (MRI) were conducted at the Texas Tech University Health Sciences Center School of Pharmacy which included components of typical residency interviews. The primary outcome compared residency match rates for MRI participants vs. non-participants. Secondary outcomes evaluated student preparedness, student and faculty feedback, and satisfaction/benefit of the event along with comparison of school vs. national match rate and assessment of those matching compared to grade point average (GPA). RESULTS: Match rates were similar between MRI participants vs. non-participants (75% vs. 73%) with significant difference in Phase I match rates between MRI participants vs. non-participants (75% vs. 51%, P = .007). MRI was significantly associated with Phase I matching in the multivariable analysis (odds ratio (OR) = 2.81, 95% CI 1.27-6.22). The overall school's match rate exceeded the national two out of three years in the quality improvement project period. GPA was the only other factor independently associated with Phase I matching (OR = 1.15, 95% CI 1.01-1.32). Students and faculty consistently reported positive feedback following participation. CONCLUSIONS: MRI are valuable and are making a difference as indicated by improved Phase I match rates for those that participated. Students and faculty reported an increase in preparedness and overall satisfaction after attending MRI.

Characterization and compensation of f0 inhomogeneity artifact in spiral hyperpolarized 13 C imaging of the human heart.

PURPOSE: This study aimed to investigate the role of regional f0 inhomogeneity in spiral hyperpolarized 13 C image quality and to develop measures to alleviate these effects. METHODS: Field map correction of hyperpolarized 13 C cardiac imaging using spiral readouts was evaluated in healthy subjects. Spiral readouts with differing duration (26 and 45 ms) but similar resolution were compared with respect to off-resonance performance and image quality. An f0 map-based image correction based on the multifrequency interpolation (MFI) method was implemented and compared to correction using a global frequency shift alone. Estimation of an unknown frequency shift was performed by maximizing a sharpness objective based on the Sobel variance. The apparent full width half at maximum (FWHM) of the myocardial wall on [13 C]bicarbonate was used to estimate blur. RESULTS: Mean myocardial wall FWHM measurements were unchanged with the short readout pre-correction (14.1 ± 2.9 mm) and post-MFI correction (14.1 ± 3.4 mm), but significantly decreased in the long waveform (20.6 ± 6.6 mm uncorrected, 17.7 ± 7.0 corrected, P = .007). Bicarbonate signal-to-noise ratio (SNR) of the images acquired with the long waveform were increased by 1.4 ± 0.3 compared to those acquired with the short waveform (predicted 1.32). Improvement of image quality was observed for all metabolites with f0 correction. CONCLUSIONS: f0 -map correction reduced blur and recovered signal from dropouts, particularly along the posterior myocardial wall. The low image SNR of [13 C]bicarbonate can be compensated with longer duration readouts but at the expense of increased f0 artifacts, which can be partially corrected for with the proposed methods.

Do the types and routes of proton pump inhibitor treatments affect clostridium difficile in ICU patients? A retrospective cohort study.

Background: : Proton pump inhibitors (PPI) are associated with Clostridium difficile infection (CDI). Impact of the route of administration is unknown.Research Design and Methods: Patients in Multiparameter Intelligent Monitoring in Intensive Care II database (MIMIC-II) from 2001 to 2008, >18 years old, admitted to medical, surgical, or cardiac ICUs were included. PPI exposures were omeprazole, esomeprazole, lansoprazole, and pantoprazole. PPI administration routes were oral or intravenous. Patients who received histamine receptor antagonists (H2RA) were the control arm. CDI was identified using ICD-9 diagnostic code 008.45. Multiple logistic regression analysis was performed to calculate odds ratios (OR).Results: The study included 16,820 patients (57% male) with a mean age of 63 (SD±17) years and hospitalization duration of 10.2 days (SD±11). Pantoprazole was the most common PPI (94%). CDI occurred in 2.4% and more in patients receiving PPIs than H2RAs (3.0% vs. 0.8%, p < 0.001). CDI prevalence increased with intravenous (95%CI = 1.69-3.39, OR 2.4) and oral (95%CI = 1.59-3.27, OR 2.3) PPI use compared to H2RAs. CDI prevalence was not associated with PPI route in the multivariable model (OR 1.07, 95%CI 0.86-1.34).Conclusions: Both intravenous and oral PPI use in the ICU were independently associated with CDI.

Pharmacists without Access to the EHR: Practicing with One Hand Tied Behind Our Backs.

Pharmacists are the most accessible healthcare professionals to the public, yet have the least amount of information from the electronic health record available to them. This lack of information makes ensuring that patients are receiving proper medications and monitoring for efficacy and safety a challenge, if not impossible in some situations. Having access to a national electronic health record would provide pharmacists with this needed information to truly engage with prescribers as fellow clinical experts in the field. Sharing prescription information for non-controlled substances would also decrease the likelihood of a patient receiving duplicative therapy from two prescribers or pharmacies that may not know what the other is doing. There are already examples of successful national data sharing including the Prescription drug Monitoring Program for controlled substances as well as the Veterans Affairs healthcare system. Therefore, our profession needs to push for nationwide access to patient electronic health records, which includes all healthcare providers. This will facilitate the inclusion of pharmacists in the optimization of the care of patients who need our expertise in managing their medication regimens as well as build better relationships with prescribing providers.

Low Prevalence of Thrombosis Prophylaxis Dose Adjustments Highlights Implications for Patient Safety.

Background: Pharmacologic thromboprophylaxis (PTP) is the mainstay prevention strategy for venous thromboembolism (VTE). PTP agents traditionally dosed, like unfractionated heparin (UFH) and enoxaparin (ENOX), are associated with failure and bleeding in obese and underweight patients, respectively. Objectives: This study aimed to describe the prevalence of unadjusted ENOX and UFH dosing for PTP based on anthropometric measures. Patients/Methods:This was a post-hoc, multicenter, cross-sectional analysis of critically ill adults receiving PTP with ENOX or UFH. The primary outcome was the prevalence of unadjusted PTP based on body mass index (BMI) and total body weight (TBW). Definitions for dose adjustments were developed based on existing literature. A secondary outcome was to identify factors associated with unadjusted dosing per BMI and TBW using multivariable generalized linear mixed-effect models. Results: The nested cohort included 172 patients (ENOX=46, UFH=126). Unadjusted PTP was observed in 118 patients (68.6%) based on BMI and 74 (43%) per TBW. When comparing UFH to ENOX, more patients who received UFH had doses unadjusted by BMI (78.6% vs. 41.3%, p<0.05) but not TBW (43.7% vs. 41.3%). Factors independently associated with unadjusted PTP per BMI were receipt of UFH (OR 6.93, 95% CI 1.06-8.77) or a BMI underweight or overweight/obese (OR 10.45, 95% CI 4.38-24.92). Having a TBW <50kg or >100kg (OR 4.85, 95% CI 2.15-10.96) were independently associated with unadjusted PTP based on TBW. Conclusions: Unadjusted dosing of PTP occurs frequently in critically ill adults receiving ENOX or UFH. This was seen in body size extremes by both BMI and TBW.

Imaging Acute Metabolic Changes in Patients with Mild Traumatic Brain Injury Using Hyperpolarized [1-13C]Pyruvate.

Traumatic brain injury (TBI) involves complex secondary injury processes following the primary injury. The secondary injury is often associated with rapid metabolic shifts and impaired brain function immediately after the initial tissue damage. Magnetic resonance spectroscopic imaging (MRSI) coupled with hyperpolarization of 13C-labeled substrates provides a unique opportunity to map the metabolic changes in the brain after traumatic injury in real-time without invasive procedures. In this report, we investigated two patients with acute mild TBI (Glasgow coma scale 15) but no anatomical brain injury or hemorrhage. Patients were imaged with hyperpolarized [1-13C]pyruvate MRSI 1 or 6 days after head trauma. Both patients showed significantly reduced bicarbonate (HCO3 -) production, and one showed hyperintense lactate production at the injured sites. This study reports the feasibility of imaging altered metabolism using hyperpolarized pyruvate in patients with TBI, demonstrating the translatability and sensitivity of the technology to cerebral metabolic changes after mild TBI.

Development and validation of a quantitative LC-MS/MS method for the simultaneous determination of ceftolozane and tazobactam in human plasma and urine.

The purpose of this work was to develop and validate a single sensitive, selective and rapid bioanalytical method to determine ceftolozane and tazobactam concentrations in human plasma and urine and to use this method to analyze samples from a human clinical study. Human plasma and urine samples were prepared by protein precipitation using a solution of acetonitrile, water and formic acid. Following protein precipitation, samples were analyzed by liquid chromatography tandem mass spectrometry. Chromatographic resolution was achieved on a Kinetex PFP column using a gradient elution, a flow rate of 0.4 mL/min, and a total run time of 5 min. Positive electrospray ionization was employed and analytes were quantitated using multi-reaction monitoring mode. Method validation was conducted in accordance with Unites States Food and Drug Administration's regulatory guidelines for bioanalytical method validation. Calibration curves were determined to linear over the range of 0.1 to 40 µg/mL for ceftolozane and 0.05 to 20 µg/mL for tazobactam. The method was determined to be accurate (-6.24 to 12.53 percent relative error), precise (less than 13.28 percent standard deviation) and sensitive in both human plasma and urine. Ceftolozane and tazobactam were determined to be stable across a battery of stability studies including autosampler, benchtop, freeze/thaw and long-term stability. This validated method successfully applied to human clinical samples to determine the concentration versus time profiles of the intravenously administered combination of Zerbaxa (ceftolozane-tazobactam) in burn patients.