“Acute urinary antibiotics”—A simple metric to identify outpatient antibiotic stewardship opportunities in renal transplant

Background: International Classification of Diseases, Tenth Edition (ICD-10) data help track outpatient antibiotic prescribing but lack validation in immunocompromised populations or subspecialty clinics for this purpose. Asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) are important stewardship targets in renal transplant (RT) patients, but they may require alternative metrics to best monitor prescribing patterns. We describe ICD-10 utilization for RT clinic encounters in which antibiotics were prescribed. We developed a metric classifying “acute urinary antibiotics” (AUA) to track antibiotic use for ASB and UTI, and we validated systematic identification of AUA to enable practical implementation. Methods: We examined RT clinic visit and telemedicine encounters from 2018 to 2021 conducted 1 month after transplant. This project was deemed non–human-subjects research by the Stanford Panel on Human Subjects in Medical Research. Results: The analytic cohort included 420 antibacterial prescriptions from 408 encounters (Fig. 1). Of 238 patients, 136 (57%) were male and 112 (47%) were Hispanic or Latino. The most common primary ICD-10 code was Z94.0 (kidney transplant status) (N = 302 of 408 encounters, 75%); 26 encounters (6%) were coded for UTI (eg, N39.0, urinary tract infection, site not specified); and 214 encounters (53%) had multiple ICD-10 codes. The R82.71 code (bacteriuria) was never used. However, 215 prescriptions (51%) were classified as AUA (Fig. 2). The validation cohort included 130 prescriptions; 59 (45%) were classified as AUA and 51 (39%) had documented intent to treat ASB or UTI (positive percent agreement, 83%; negative percent agreement, 97%) (Table 1). For patients >1 month after transplant, the positive percent agreement was 95% and the negative percent agreement was 98%. Of 51 patients receiving AUA, 32 (63%) were asymptomatic despite frequently having a code for UTI (Fig. 3). Conclusions: ICD-10 coding may not be helpful in monitoring antibiotic prescribing in RT patients. The AUA metric offers a practical alternative to track antibiotic prescribing for urinary syndromes and reliably correlates with physician intent. Monitoring AUA prescribing rates could help identify opportunities to optimize antibiotic use in this complex outpatient setting

Evaluation of the Infectious Diseases Society of America’s Core Antimicrobial Stewardship Curriculum for Infectious Diseases Fellows

Background Antimicrobial stewardship (AS) programs are required by Centers for Medicare and Medicaid Services and should ideally have infectious diseases (ID) physician involvement; however, only 50% of ID fellowship programs have formal AS curricula. The Infectious Diseases Society of America (IDSA) formed a workgroup to develop a core AS curriculum for ID fellows. Here we study its impact. Methods ID program directors and fellows in 56 fellowship programs were surveyed regarding the content and effectiveness of their AS training before and after implementation of the IDSA curriculum. Fellows’ knowledge was assessed using multiple-choice questions. Fellows completing their first year of fellowship were surveyed before curriculum implementation (“pre-curriculum”) and compared to first-year fellows who complete the curriculum the following year (“post-curriculum”). Results Forty-nine (88%) program directors and 105 (67%) fellows completed the pre-curriculum surveys; 35 (64%) program directors and 79 (50%) fellows completed the post-curriculum surveys. Prior to IDSA curriculum implementation, only 51% of programs had a “formal” curriculum. After implementation, satisfaction with AS training increased among program directors (16% to 68%) and fellows (51% to 68%). Fellows’ confidence increased in 7/10 AS content areas. Knowledge scores improved from a mean of 4.6 to 5.1 correct answers of 9 questions (P = .028). The major hurdle to curriculum implementation was time, both for formal teaching and for e-learning. Conclusions Effective AS training is a critical component of ID fellowship training. The IDSA Core AS Curriculum can enhance AS training, increase fellow confidence, and improve overall satisfaction of fellows and program directors

Immunodeficiency-Related Vaccine-Derived Poliovirus (Ivdpv) Cases: A Systematic Review And Implications For Polio Eradication

Background: Vaccine-derived polioviruses (VDPVs), strains of poliovirus mutated from the oral polio vaccine, pose a challenge to global polio eradication. Immunodeficiency-related vaccine-derived polioviruses (iVDPVs) are a type of VDPV which may serve as sources of poliovirus reintroduction after the eradication of wild-type poliovirus. This review is a comprehensive update of confirmed iVDPV cases published in the scientific literature from 1962 to 2012, and describes clinically relevant trends in reported iVDPV cases worldwide. Methods: We conducted a systematic review of published iVDPV case reports from January 1960 to November 2012 from four databases. We included cases in which the patient had a primary immunodeficiency, and the vaccine virus isolated from the patient either met the sequencing definition of VDPV (\u3e1% divergence for serotypes 1 and 3 and \u3e0.6% for serotype 2) and/or was previously reported as an iVDPV by the World Health Organization. Results: We identified 68 iVDPV cases in 49 manuscripts reported from 25 countries and the Palestinian territories. 62% of case patients were male, 78% presented clinically with acute flaccid paralysis, and 65% were iVDPV2. 57% of cases occurred in patients with predominantly antibody immunodeficiencies, and the overall all-cause mortality rate was greater than 60%. The median age at case detection was 1.4 years [IQR: 0.8, 4.5] and the median duration of shedding was 1.3 years [IQR: 0.7, 2.2]. We identified a poliovirus genome VP1 region mutation rate of 0.72% per year and a higher median percent divergence for iVDPV1 cases. More cases were reported from high income countries, which also had a larger age variation and different distribution of immunodeficiencies compared to upper and lower middle-income countries. Conclusion: Our study describes the incidence and characteristics of global iVDPV cases reported in the literature in the past five decades. It also highlights the regional and economic disparities of reported iVDPV cases

Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis

<div><p>Background</p><p>Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited.</p><p>Methods</p><p>We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries.</p><p>Results</p><p>We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were$15,620 (IQR: $877 to$48,376); $54,871 (IQR:$787 to $115,026) and$49 (IQR: $15 to$1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target vaccination strategy depended on the inclusion of the herd protection effect.</p><p>Conclusions</p><p>Inclusion of herd-protection effects in CEAs had a substantial impact in the estimated ICERs and made target-vaccination strategies more attractive options in almost half of the cases where ICERs were above the societal-willingness to pay threshold without herd-protection. More empirical epidemiologic data are needed to determine the size of herd-protection effects across diverse settings and also the size of negative vaccine effects, e.g. from serotype substitution.</p></div

Scatterplot of ICERs (per-QALY gained, per-LY gained and per-DALY averted) with vs. without herd-protection across all four vaccines.

<p>Y-axis: ICERs without herd protection and X-axis: ICERs with herd-protection (values inflated to 2016 US dollars, [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172414#pone.0172414.ref029" target="_blank">29</a>]); Dashed lines in the horizontal and vertical axis correspond to $50,000 threshold without and with herd-protection respectively. (ICERs in the left upper quadrant indicate cases where ICERs were >$50,000 without herd-protection and crossed that threshold with Herd Protection).</p

Differences in ICER/QALY, ICER/LY and ICER/DALY with vs. without Herd protection^*.

<p>Differences in ICER/QALY, ICER/LY and ICER/DALY with vs. without Herd protection^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172414#t002fn002" target="_blank">*</a>}.</p