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As of August 2021, there were three COVID-19 vaccines available in the United States for the prevention of coronavirus 2019 (COVID-19). The purpose of this narrative review is to examine the early experience from the Emergency Use Authorization (EUA) of BNT162b2 (Pfizer, Inc./BioNTech), mRNA-1273 (Moderna, Inc.), and Ad26.COV2.S (Johnson and Johnson/Janssen Global Services, LLC) through July 2021. The EUA data from the clinical trials have largely been corroborated by real-world effectiveness investigations post-authorization. These studies indicate that immunity is obtained within 2weeks post-vaccination and may endure for 6months. The immunity conferred by the vaccines may also be effective against SARS-CoV-2 variants of concern. Additionally, populations not included in the emergency use authorization studies may also benefit from vaccination. This look back at the initial clinical experience can be used by the global community to inform and develop COVID-19 vaccine programs.

Among patients with methicillin-resistant Staphylococcus aureus bacteremia, vancomycin-associated acute kidney injury increased as a function of the day 2 area under the curve (AUC), even for daily AUCs within the recommended therapeutic range (400–600). Further data are needed to determine if daily AUCs

The Accelerate Pheno and BacT/Alert Virtuo systems may improve bacteremia management. Here, we evaluated the impact of both devices on outcomes in patients with sepsis and concurrent Gram-negative bacteremia. This quasiexperimental study included a retrospective preimplementation and a prospective postimplementation group. Patients ≥18 years old with Gram-negative bacteremia were included. Patients with neutropenia, pregnant patients, those who were transferred from an outside hospital with active bloodstream infections, and those with polymicrobial bacteremia were excluded. Blood culture incubation in the BacT/Alert 3D device and microdilution antimicrobial susceptibility testing from culture plate growth were used prior to implementation of the BacT/Alert Virtuo and Accelerate Pheno systems. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) identification directly from blood culture was used pre- and postimplementation. Time to Gram stain results, identification, susceptibility reporting, initiation of narrow-spectrum Gram-negative therapy at 72 h, 30-day inpatient mortality, sepsis resolution, and length of hospital stay were evaluated. A total of 116 patients were included (63 preimplementation, 53 postimplementation). Median times to Gram stain and susceptibility results were significantly shorter postimplementation (P

Combination therapy with vancomycin and piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) compared with monotherapy with either agent. This retrospective, matched cohort study was conducted to assess the comparative incidence of AKI due to combination therapy in patients receiving vancomycin and TZP in combination or as monotherapy. Patients aged ≥18 years admitted to Albany Medical Center (Albany, NY) between September 2013 and August 2014 who had received therapy for at least two consecutive days were included. Patients who were pregnant, neutropenic, had AKI on admission or with cystic fibrosis were excluded. Patients were matched on baseline risk of AKI. The main outcome of interest was AKI, defined as an increase in serum creatinine of ≥0.3 mg/L or ≥50% within 48 h. Secondary outcomes evaluated were length of hospital and ICU stay and inpatient mortality associated with AKI. The risk of AKI was 7.0%, 8.5% and 26.8% in the vancomycin monotherapy, TZP monotherapy and combination groups, respectively (P0.001). In the multivariate analysis, combination therapy was independently associated with an increased odds of AKI (adjusted odds ratio = 4.406, 95% confidence interval 1.472-13.188) compared with vancomycin monotherapy. The excess risk of combination therapy was 11.3%. In this matched cohort study, there was an increased incidence of AKI in patients receiving vancomycin and TZP combination therapy. Further research is needed to determine the individual strategies to best prevent inpatient AKI in patients receiving this combination therapy.

Abstract Introduction Complicated urinary tract infections (cUTI) are common infections. Despite their frequency, limited data are available on the incidence and healthcare burden associated with cUTIs. This study details the epidemiology and 30-day health care resource utilization associated with cUTI in the US. Methods Retrospective study of PharmMetrics Plus database from 1/1/2013 to 12/31/2017. Inclusion criteria: age ≥ 18 years, ICD-9/10 cUTI diagnosis, and continuous enrollment for ≥ 6 months pre- and ≥ 30 days post-index dates. Two mutually exclusive study cohorts for cUTI patients were identified based on the setting of the first observed cUTI diagnosis (inpatient (IP) and outpatient (OP)). Results In total 543,502 adults with cUTI met the inclusion criteria (104,866 IP cohort; 438,636 OP cohort). Mean (SD) age was 48.1 (16.5) years and 68.1% were female. The overall incidence of cUTI was 1.01%, equating to approximately 2,882,195 annual cUTI cases in the US. In the IP cohort, overall median (IQR) 30-day health care costs were $13,028 ($4,855-$26,781). Median (IQR) costs for the initial admission were $9,441 ($2,079-$19,027), with median (IQR) length of stay (LOS) of 4 (3-8) days. Among IP patients, 12,933 (12.3%) had a subsequent readmission. In the OP cohort, median (IQR) 30-day health care costs were $1,531 ($305-$4,998). Of OP patients, 40,457 (9.2%) had a 30-day admission. Conclusions This study demonstrates that the economic burden associated with cUTIs is substantial, especially among patients requiring hospitalization. These findings highlight the need for new treatment approaches and antibiotics that avert hospitalization and reduce LOS.

Background Statewide tracking and reporting is an outpatient antimicrobial stewardship tool that may be useful for many stakeholders. However, to date, these evaluations have been limited. This study aimed to track and report outpatient antibiotic prescribing in Medicare Part B enrollees diagnosed with cystitis in the outpatient setting. Methods This was a retrospective, cohort study of Medicare Part B enrollees in New York State. Inclusion criteria include outpatient visit in 2016 or 2017, cystitis diagnosis code, and oral antibiotic prescription ≤3 days after diagnosis of cystitis. Antibiotics were categorized as first-line, oral β-lactams, fluoroquinolones, or other per Infectious Diseases Society of America acute uncomplicated cystitis guidelines. Data were stratified by sex. Annual prescriptions proportions were compared using χ 2 test or Fisher’s exact test as appropriate. Results A total of 50 658 prescriptions were included. For females’ prescriptions, first line increased (41.5% vs 43.8%, P < .0001), oral β-lactams increased (17.8% vs 20.5%, P < .0001), fluoroquinolones decreased (34.1% vs 29.1%, P < .0001), and other increased (6.5% vs 6.6%, P = .76) in 2017. For males’ prescriptions, first line increased (25.2% vs 26.7%, P = .11), oral β-lactams increased (23.1% vs 26.2%, P = .0003), fluoroquinolones decreased (44.0% vs 39.3%, P < .0001), and other remained unchanged (7.8% vs 7.8%, P = .92) in 2017. Conclusions Guideline concordant therapy prescribing for cystitis increased among Medicare Part B beneficiaries in New York State between 2016 and 2017. However, there was still a high prevalence of fluoroquinolone prescribing. These data highlight the need for additional outpatient antimicrobial stewardship efforts in New York State.

Purpose Antimicrobial stewardship programs (ASPs) can be aided by using rapid diagnostics (RDT). However, there are limited data evaluating the impact of ASPs and RDT on sepsis outcomes in the setting of the new Sepsis-3 guidelines. This study evaluates the impact of a low-resource method for ASPs with RDT on sepsis outcomes. Methods This was a prospective, quasi-experimental study with a retrospective double pretest. Patients ≥ 18 years old with sepsis and concurrent bacteremia or fungemia were included; patients who were pregnant, had polymicrobial septicemia or who were transferred from an outside hospital were excluded. In the first pretest (O1), polymerase chain reaction was used to identify Staphylococcal species from positive blood cultures, and traditional laboratory techniques were used to identify other species. Matrix-assisted laser desorption ionization time-of-flight mass spectroscopy and FilmArray were implemented in the second pretest (O2), and twice daily blood culture review was implemented in the posttest (O3). Results A total of 394 patients (157 in O1, 176 in O2, 61 in O3) were enrolled. Clinical response was 73.2%, 83.5%, and 88.5% in O1, O2, and O3, respectively, p = 0.013. By Cox regression, the O3 was associated with improved time to clinical response (hazard ratio, 1.388; 95% confidence interval, 1.004-1.919) as compared with O1. Mortality, hospital length of stay, and intensive care unit length of stay were unchanged between groups. Conclusion Twice-daily blood culture review may be useful for implementing rapid diagnostics within low-resource ASPs. Further research is needed to identify the optimal method of blood culture follow-up within low-resource settings.

Background: Use of alternative antimicrobials to vancomycin is a potential strategy to reduce acute kidney injury (AKI) in high-risk patients, but current data do not support widespread adoption of this practice. Objective: To determine the efficacy of early switch to a nonnephrotoxic alternative for prevention of AKI in high-risk patients who receive vancomycin. Methods: This was an IRB-approved, prospective randomized controlled trial in a single, tertiary care academic medical center. Patients initially prescribed vancomycin between October 2011 to April 2013 with at least 2 risk factors for AKI were included. Treatment randomization was stratified by indication for therapy. Patients were randomized to continuation of dose-optimized vancomycin or early switch to an alternative antimicrobial agent. The primary end point was nephrotoxicity by consensus guideline definition adjudicated by blinded review; the secondary end point was AKI network–defined AKI. Results: A total of 103 patients were randomized; 100 were included in the modified intent-to-treat population, 51 in the vancomycin group and 49 in the alternative group. The incidence of nephrotoxicity was 6.1% in the alternative therapy arm and 9.8% in the vancomycin group ( P = 0.72). The incidence of AKI was 32.7% in the alternative therapy group and 31.4% in the vancomycin group ( P = 0.89). Conclusions: No significant difference in nephrotoxicity or AKI was detected among patients treated with alternative antimicrobials compared with vancomycin. The use of alternative antimicrobial therapy instead of vancomycin solely for the purpose of preventing AKI in high-risk patients does not appear to be warranted.

To the Editor,Drug shortages may lead to less prescribing of medications due to needed restrictions or reduced inventory. We read with interest a report in the present journal on an antimicrobial s...

International guidelines recommend using local susceptibility data to direct empiric therapy for acute uncomplicated cystitis. We evaluated outpatient urinary isolate susceptibility trends in New York State. Nitrofurantoin had the lowest resistance prevalence whereas trimethoprim-sulfamethoxazole and fluoroquinolones had higher prevalences. This study highlights the need for local outpatient antimicrobial stewardship programs.

This study evaluated the predictive performance of a Bayesian PK estimation method (ADAPT V) to estimate the 24-h vancomycin area under the curve (AUC) with limited pharmacokinetic (PK) sampling in adult obese patients receiving vancomycin for suspected or confirmed Gram-positive infections. This was an Albany Medical Center Institutional Review Board-approved prospective evaluation of 12 patients. Patients had a median (95% confidence interval) age of 61 years (39 to 71 years), a median creatinine clearance of 86 ml/min (75 to 120 ml/min), and a median body mass index of 45 kg/m 2 (40 to 52 kg/m 2 ). For each patient, five PK concentrations were measured, and four different vancomycin population PK models were used as Bayesian priors to estimate the vancomycin AUC (AUC FULL ). Using each PK model as a prior, data-depleted PK subsets were used to estimate the 24-h AUC (i.e., peak and trough data [AUC PT ], midpoint and trough data [AUC MT ], and trough-only data [AUC T ]). The 24-h AUC derived from the full data set (AUC FULL ) was compared to the AUC derived from data-depleted subsets (AUC PT , AUC MT , and AUC T ) for each model. For the four sets of analyses, AUC FULL estimates ranged from 437 to 489 mg·h/liter. The AUC PT provided the best approximation of the AUC FULL ; AUC MT and AUC T tended to overestimate AUC FULL . Further prospective studies are needed to evaluate the impact of AUC monitoring in clinical practice, but the findings from this study suggest that the vancomycin AUC can be estimated with good precision and accuracy with limited PK sampling using Bayesian PK estimation software.

Ceftaroline fosamil (ceftaroline hereafter) is the latest addition to the armamentarium for the treatment of patients with community-acquired pneumonia (CAP). It is currently approved by the Food and Drug Administration (FDA) for community-acquired bacterial pneumonia (CABP), which is a recent FDA indication that centers on individuals with documented bacterial pneumonias that arise in the community setting. The purpose of this review is to summarize and discuss the major findings from the Phase III CAP clinical trials as well as the clinical experience with ceftaroline among patients with CAP in the “Ceftaroline Assessment Program and Teflaro® Utilization Registry” (CAPTURE). In its two Phase III CAP trials, ceftaroline was compared to ceftriaxone among adults with radiographically confirmed CAP requiring hospitalization who were classified as Pneumonia Outcomes Research Team (PORT) risk class III or IV. Among patients with CAP, clinical success at test of cure was 84.3% vs 77.7% (difference 6.6%, 95% confidence interval [CI]: 1.6–11.8%) in those treated with ceftaroline and ceftriaxone, respectively, across the two Phase III clinical trials. Among patients with a culture-confirmed CABP, day 4 response rates were numerically higher, albeit non-significant, among patients that received ceftaroline vs. ceftriaxone (69.5% for ceftaroline vs. 59.4% for ceftriaxone, difference 10.1%, 95% CI, −0.6% to 20.6%). The efficacy of ceftaroline is supported by real-world observational data from CAPTURE for patients with both CAP and CABP. In addition, the CAPTURE program afforded an opportunity to assess the outcomes of patients who were excluded or limited in the original Phase III trials in a non-comparative fashion. These underrepresented patient populations with CAP included: patients that received prior antibiotics, patients in the ICU, patients with severe renal dysfunction, and those with methicillin-resistant Staphylococcus aureus (MRSA) isolated from respiratory or blood culture. As CAPTURE is a retrospective, non-comparator convenience sample registry, all the findings need to be interpreted with caution. Electronic supplementary material The online version of this article (doi:10.1007/s40121-014-0036-8) contains supplementary material, which is available to authorized users.

OBJECTIVETo evaluate time to clinical response before and after implementation of rapid blood culture identification technologies.DESIGNBefore-and-after trial.SETTINGLarge, tertiary, urban, academic health-sciences center.PATIENTSPatients >18 years old with sepsis and concurrent bacteremia or fungemia were included in the study; patients who were pregnant, had polymicrobial septicemia, or were transferred from an outside hospital were excluded.INTERVENTIONPrior to the intervention, polymerase chain reaction was used to identify Staphylococcus species from positive blood cultures, and traditional laboratory techniques were used to identify non-staphylococcal species. After the intervention, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) assay and FilmArray were also used to identify additional species. During both periods, the antimicrobial stewardship team provided prospective audit and feedback for all patients on antibiotics.RESULTSA total of 219 patients were enrolled in the study: 115 patients prior to the intervention and 104 after the intervention. The median time to clinical response was statistically significantly shorter in the postintervention group than in the preintervention group (2 days vs 4 days, respectively; P=.002). By Cox regression, the implementation of MALDI-TOF and FilmArray was associated with shorter time to clinical response (hazard ratio [HR], 1.360; 95% confidence interval [CI], 1.018–1.816). After controlling for potential confounders, the study group was not independently associated with clinical response (adjusted HR, 1.279; 95% CI, 0.955–1.713). Mortality was numerically, but not statistically significantly, lower in the postintervention group than in the preintervention group (7.6% vs 11.4%; P=.342).CONCLUSIONSIn the setting of an existing antimicrobial stewardship program, implementation of MALDI-TOF and FilmArray was associated with improved time to clinical response. Further research is needed to fully describe the effect of antimicrobial stewardship programs on time to clinical response.Infect Control Hosp Epidemiol 2016;37:916–923

Background Outpatient prescribing for acute uncomplicated cystitis is a significant driver of antimicrobial use. Empiric therapy should be based on local susceptibility data. However, there is limited guidance on regional susceptibility trends in outpatient settings. This study describes the epidemiology and prevalence of antimicrobial resistance in uropathogens in New York State outpatient settings to help inform empiric treatment decisions. Methods Retrospective analysis of positive urine cultures sent to Quest Diagnostics in 2016 from outpatient settings. Cultures that grew ≥105 CFU/mL were included from 17 NYS counties. Bacterial identification and antimicrobial sensitivities were determined on the Vitek-2 using CLSI M-100 S-25 breakpoints. Data were summarized as proportions and stratified by age ( Results Over 78,000 isolates were included (Table 1). The most prevalent isolates were Escherichia coli (65.2%), Enterococcus spp. (11.9%), and Klebsiella pneumoniae (9.9%). E. coli was highly susceptible to nitrofurantoin (NTF, 97.2%) and cefazolin (CFZ, 89.9%) and less susceptible to trimethoprim–sulfamethoxazole (TMP-SMX, 72.9%) and ciprofloxacin (CIP, 78.0%). Enterococcus spp. was highly susceptible to NTF (99.0%) and ampicillin (99.8%). K. pneumoniae was highly susceptible to TMP-SMX (90.0%) and CIP (95.2%) and markedly less susceptible to NTF (42.0%). E. coli was more prevalent in females (69.7% vs. 39.6%, P < 0.001). Enterococcus was more prevalent in males (39.6% vs. 10.1%, P < 0.001). The prevalence of K. pneumoniae was similar in men and women (9.6% vs. 10.1%, P = 0.08). Resistance was more prevalent in males (NTF: 6.3% vs. 4.2%; TMP-SMX: 26.3% vs. 22.7%; CIP: 35% vs. 17.3%) and for adults ≥65 (NTF: 6.2% vs. 3.6%; TMP-SMX: 25.1% vs. 22.1%; CIP: 30.0% vs. 14.0%) P < 0.001 for all comparisons. Conclusion NTF appears to be the best empiric choice for outpatient treatment of acute uncomplicated cystitis in New York State. TMP-SMX and ciprofloxacin should be avoided empirically. These data also highlight the necessity to obtain uropathogen sensitivity data to confirm empiric therapy or make appropriate adjustments in the outpatient setting. Table 1. Summary of Antimicrobial Susceptibilities Disclosures T. P. Lodise Jr., Motif BioSciences: Board Member, Consulting fee.

Purpose Improvements in medication use achieved by pharmacy generalists using a care bundle approach to antimicrobial stewardship are reported. Methods A six-month prospective, repeated-treatment, quasi-experimental study involving three month-long intervention periods and three month-long control periods was conducted in the setting of an existing antimicrobial stewardship program at a large hospital. The intervention involved prospective audit and feedback conducted by pharmacy generalists who were trained in an antimicrobial stewardship care bundle approach. During control months, a pharmacy generalist who was not trained in antimicrobial stewardship rounded with the multidisciplinary team and provided standard-of-care pharmacy services. The primary endpoint was compliance with a care bundle of four antimicrobial stewardship metrics: documentation of indication for therapy in the medical record, selection of empirical therapy according to institutional guidelines, documented performance of indicated culture testing, and deescalation of therapy when indicated. Results Two-hundred eighty-six patients were enrolled in the study: 124 in the intervention group and 162 in the control group. The cumulative rate of full compliance with all care bundle components during the six-month study was significantly greater during intervention months than during control months (68.5% versus 45.7%, p < 0.001). After adjusting for infection type, antimicrobial stewardship provided by an intervention-group pharmacist was associated with improved care bundle compliance (adjusted odds ratio, 2.70; p < 0.001). No significant differences in patient outcomes during intervention and control months were detected. Conclusion Pharmacy generalists trained to comply with a systematic care bundle approach enhanced the quality of antimicrobial management.

Background Pseudomonas aeruginosa septicemia (PAS) is associated with high mortality rates and substantial resource utilization; however, the burden of PAS in the United States in recent years is unknown. Methods This was a retrospective analysis of the U.S. National Hospital Discharge Surveys from 1996-2010. Adult patients with an ICD-9-CM code for PAS (038.43) were included. Incidence, in-hospital mortality, and hospital length of stay (LOS) for PAS discharges were reported. Incidence was calculated as PAS discharges per 10,000 total adult discharges. Results Overall, 213,553 patients had a PAS discharge diagnosis during the study period. Patients had a median (interquartile range [IQR]) age of 69 (55-78) years and were predominately men (61%) and white (75%). PAS incidence declined from 6.5 per 10,000 in 1996 to 3.1 per 10,000 in 2001 and then increased to 6.5 per 10,000 in 2010. PAS incidence was highest in the Northeast (7.6 per 10,000) and lowest in the South (6.2 per 10,000). The overall mortality rate was 16%, but this ranged from 10%-26% over the study period. Median LOS was 10 (IQR, 6-19) days, and this varied over the study period (8-13 days). Conclusions The incidence of PAS has increased among hospitalized adults in the United States since 2001, with little evidence of improvement in mortality or LOS.

Introduction Little is known regarding age-related risk of nephrotoxicity during vancomycin therapy after the publication of the 2009 vancomycin consensus guidelines for therapeutic drug monitoring. We sought to evaluate incidence and risk factors for acute kidney injury in three age groups. Methods Matched cohort study of patients receiving vancomycin, grouped by age: young adults (18–64 years), older adults (65–79 years) and very elderly (≥80 years), matched on previously published risk factors for nephrotoxicity. Outcomes included traditional vancomycin nephrotoxicity and Acute Kidney Injury Network-modified definition of nephrotoxicity. Results The incidence of acute kidney injury was 34.1% vs. 34.1% vs. 31.8% in the young, older adults and very elderly groups, respectively (p = 0.97). In the logistic regression model, after adjusting for baseline risk factors, age was not a significant predictor of acute kidney injury. Lower respiratory tract infection (adjusted odds ratio [aOR] 5.18; 95% confidence interval [CI] 2.15–12.41) and duration of treatment (aOR 1.12; 95% CI 1.03–1.22) were found to be independently associated with outcome. Conclusion No differences in risk of acute kidney injury were identified between young, older, and very elderly adults when adjusting for other risk factors. Further research is required to identify strategies to optimize the safety of vancomycin in the aging population. Electronic supplementary material The online version of this article (doi:10.1007/s40121-013-0022-6) contains supplementary material, which is available to authorized users.

Introduction Antimicrobial prescribing in the emergency department is predominantly empiric, with final microbiology results either unavailable or reported after most patients are discharged home. Systematic follow-up processes are needed to ensure appropriate antimicrobial therapy at this transition of care. The objective of this study was to assess the impact of a culture follow-up (CFU) program on the frequency of emergency department (ED) revisits within 72 h and hospital admissions within 30 days compared to the historical standard of care (SOC). Additionally, infection characteristics and antimicrobial therapy were compared. Methods A single group, pre-test post-test quasi-experimental study was conducted comparing a retrospective SOC group to a prospective CFU group. CFU was implemented using computerized decision-support software and a multidisciplinary team of pharmacists and emergency physician staff. Results Over the four-month intervention period the CFU group evaluated 197 cultures and modified antimicrobial therapy in 25.5%. The rate of combined ED revisits within 72 h and hospital admissions within 30 days was 16.9% in the SOC group and 10.2% in the CFU group (p = 0.079). When evaluating the uninsured population alone, revisits to the ED within 72 h were reduced from 15.3% in the SOC group to 2.4% in the CFU group (p = 0.044). Conclusion Implementation of a multidisciplinary CFU program was associated with a reduction in ED revisits within 72 h and hospital admissions within 30 days. One-fourth of patients required post-discharge intervention, representing a large need for antimicrobial stewardship expansion to ED practice models. Electronic supplementary material The online version of this article (doi:10.1007/s40121-014-0026-x) contains supplementary material, which is available to authorized users.