Outpatient visits and antibiotic use due to higher valency pneumococcal vaccine serotypes.

BACKGROUND: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in U.S. children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national healthcare surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval 1.8-3.9) visits and 2.4 (1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (11.2-20.4) visits and 13.2 (9.9-18.0) antibiotic prescriptions annually per 1,000 children. PCV15/20-additional serotypes account for 0.4% (0.2-0.6%) and 2.1% (1.5-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for >5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.

Impact of the COVID-19 Pandemic on Inpatient Antibiotic Use in the United States, January 2019 Through July 2022.

Antimicrobial use data reported to the National Healthcare Safety Network's Antimicrobial Use and Resistance Module between January 2019 and July 2022 were analyzed to assess the impact of the COVID-19 pandemic on inpatient antimicrobial use.

Antibiotic Stewardship in Outpatient Telemedicine: Adapting Centers for Disease Control and Prevention Core Elements to Optimize Antibiotic Use.

The rapid expansion of telemedicine has highlighted challenges and opportunities to improve antibiotic use and effectively adapt antibiotic stewardship best practices to outpatient telemedicine settings. Antibiotic stewardship integration into telemedicine is essential to optimize antibiotic prescribing for patients and ensure health care quality. We performed a narrative review of published literature on antibiotic prescribing and stewardship in outpatient telemedicine to inform the adaptation of the Core Elements of Outpatient Antibiotic Stewardship framework to outpatient telemedicine settings. Our narrative review suggests that in-person antibiotic stewardship interventions can be adapted to outpatient telemedicine settings. We present considerations for applying the Core Elements of Outpatient Antibiotic Stewardship to outpatient telemedicine which builds upon growing evidence describing care delivery and quality improvement in this setting. Additional applied implementation research is necessary to inform the application of effective, sustainable, and equitable antibiotic stewardship interventions across the spectrum of outpatient telemedicine.

Phase 1 Open-Label Dose Escalation Trial for the Development of a Human Bacillus Calmette-Guérin Challenge Model for Assessment of Tuberculosis Immunity In Vivo.

BACKGROUND: A controlled human infection model for assessing tuberculosis (TB) immunity can accelerate new vaccine development. METHODS: In this phase 1 dose escalation trial, 92 healthy adults received a single intradermal injection of 2 × 106 to 16 × 106 colony-forming units of Bacillus Calmette-Guérin (BCG). The primary endpoints were safety and BCG shedding as measured by quantitative polymerase chain reaction, colony-forming unit plating, and MGIT BACTEC culture. RESULTS: Doses up to 8 × 106 were safe, and there was evidence for increased BCG shedding with dose escalation. The MGIT time-to-positivity assay was the most consistent and precise measure of shedding. Power analyses indicated that 10% differences in MGIT time to positivity (area under the curve) could be detected in small cohorts (n = 30). Potential biomarkers of mycobacterial immunity were identified that correlated with shedding. Transcriptomic analysis uncovered dose- and time-dependent effects of BCG challenge and identified a putative transcriptional TB protective signature. Furthermore, we identified immunologic and transcriptomal differences that could represent an immune component underlying the observed higher rate of TB disease incidence in males. CONCLUSIONS: The safety, reactogenicity, and immunogenicity profiles indicate that this BCG human challenge model is feasible for assessing in vivo TB immunity and could facilitate the vaccine development process. CLINICAL TRIALS REGISTRATION: NCT01868464 (ClinicalTrials.gov).

Trends in Prescribing of Antibiotics and Drugs Investigated for Coronavirus Disease 2019 (COVID-19) Treatment in US Nursing Home Residents During the COVID-19 Pandemic.

BACKGROUND: Trends in prescribing for nursing home (NH) residents, which may have been influenced by the coronavirus disease 2019 (COVID-19) pandemic, have not been characterized. METHODS: Long-term care pharmacy data from 1944 US NHs were used to evaluate trends in prescribing of antibiotics and drugs that were investigated for COVID-19 treatment, including hydroxychloroquine, famotidine, and dexamethasone. To account for seasonal variability in antibiotic prescribing and decreased NH occupancy during the pandemic, monthly prevalence of residents with a prescription dispensed per 1000 residents serviced was calculated from January to October and compared as relative percent change from 2019 to 2020. RESULTS: In April 2020, prescribing was significantly higher in NHs for drugs investigated for COVID-19 treatment than 2019; including hydroxychloroquine (+563%, 95% confidence interval [CI]: 5.87, 7.48) and azithromycin (+150%, 95% CI: 2.37, 2.63). Ceftriaxone prescribing also increased (+43%, 95% CI: 1.34, 1.54). Prescribing of dexamethasone was 36% lower in April (95% CI: .55, .73) and 303% higher in July (95% CI: 3.66, 4.45). Although azithromycin and ceftriaxone prescribing increased, total antibiotic prescribing among residents was lower from May (-5%, 95% CI: .94, .97) through October (-4%, 95% CI: .94, .97) in 2020 compared to 2019. CONCLUSIONS: During the pandemic, large numbers of residents were prescribed drugs investigated for COVID-19 treatment, and an increase in prescribing of antibiotics commonly used for respiratory infections was observed. Prescribing of these drugs may increase the risk of adverse events, without providing clear benefits. Surveillance of NH prescribing practices is critical to evaluate concordance with guideline-recommended therapy and improve resident safety.

Advancing Diagnostic Stewardship for Healthcare-Associated Infections, Antibiotic Resistance, and Sepsis.

Diagnostic stewardship means ordering the right tests for the right patient at the right time to inform optimal clinical care. Diagnostic stewardship is an integral part of antibiotic stewardship efforts to optimize antibiotic use and improve patient outcomes, including reductions in antibiotic resistance and treatment of sepsis. The Centers for Disease Control and Prevention's Division of Healthcare Quality Promotion hosted a meeting on improving patient safety through diagnostic stewardship with a focus on use of the laboratory. At the meeting, emerging issues in the field of diagnostic stewardship were identified, awareness of these issues among stakeholders was raised, and strategies and interventions to address the issues were discussed-all with an emphasis on improved outcomes and patient safety. Here, we summarize the key takeaways of the meeting including needs for diagnostic stewardship implementation, promising future avenues for diagnostic stewardship implementation, and areas of needed research.

White paper on antimicrobial stewardship in solid organ transplant recipients.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a "one-size-fits-all" style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Identifying Higher-Volume Antibiotic Outpatient Prescribers Using Publicly Available Medicare Part D Data - United States, 2019.

Antibiotic prescribing can lead to adverse drug events and antibiotic resistance, which pose ongoing urgent public health threats (1). Adults aged ≥65 years (older adults) are recipients of the highest rates of outpatient antibiotic prescribing and are at increased risk for antibiotic-related adverse events, including Clostridioides difficile and antibiotic-resistant infections and related deaths (1). Variation in antibiotic prescribing quality is primarily driven by prescribing patterns of individual health care providers, independent of patients' underlying comorbidities and diagnoses (2). Engaging higher-volume prescribers (the top 10% of prescribers by antibiotic volume) in antibiotic stewardship interventions, such as peer comparison audit and feedback in which health care providers receive data on their prescribing performance compared with that of other health care providers, has been effective in reducing antibiotic prescribing in outpatient settings and can be implemented on a large scale (3-5). This study analyzed data from the Centers for Medicare & Medicaid Services (CMS) Part D Prescriber Public Use Files (PUFs)* to describe higher-volume antibiotic prescribers in outpatient settings compared with lower-volume prescribers (the lower 90% of prescribers by antibiotic volume). Among the 59.4 million antibiotic prescriptions during 2019, 41% (24.4 million) were prescribed by the top 10% of prescribers (69,835). The antibiotic prescribing rate of these higher-volume prescribers (680 prescriptions per 1,000 beneficiaries) was 60% higher than that of lower-volume prescribers (426 prescriptions per 1,000 beneficiaries). Identifying health care providers responsible for a higher volume of antibiotic prescribing could provide a basis for additional assessment of appropriateness and outreach. Public health organizations and health care systems can use publicly available data to guide focused interventions to optimize antibiotic prescribing to limit the emergence of antibiotic resistance and improve patient outcomes.

Trends in US Outpatient Antibiotic Prescriptions During the Coronavirus Disease 2019 Pandemic.

BACKGROUND: The objective of our study was to describe trends in US outpatient antibiotic prescriptions from January through May 2020 and compare with trends in previous years (2017-2019). METHODS: We used data from the IQVIA Total Patient Tracker to estimate the monthly number of patients dispensed antibiotic prescriptions from retail pharmacies from January 2017 through May 2020. We averaged estimates from 2017 through 2019 and defined expected seasonal change as the average percent change from January to May 2017-2019. We calculated percentage point and volume changes in the number of patients dispensed antibiotics from January to May 2020 exceeding expected seasonal changes. We also calculated average percent change in number of patients dispensed antibiotics per month in 2017-2019 versus 2020. Data were analyzed overall and by agent, class, patient age, state, and prescriber specialty. RESULTS: From January to May 2020, the number of patients dispensed antibiotic prescriptions decreased from 20.3 to 9.9 million, exceeding seasonally expected decreases by 33 percentage points and 6.6 million patients. The largest changes in 2017-2019 versus 2020 were observed in April (-39%) and May (-42%). The number of patients dispensed azithromycin increased from February to March 2020 then decreased. Overall, beyond-expected decreases were greatest among children (≤19 years) and agents used for respiratory infections, dentistry, and surgical prophylaxis. CONCLUSIONS: From January 2020 to May 2020, the number of outpatients with antibiotic prescriptions decreased substantially more than would be expected because of seasonal trends alone, possibly related to the coronavirus disease 2019 pandemic and associated mitigation measures.

Opportunities to Improve Antibiotic Prescribing in Outpatient Hemodialysis Facilities: A Report From the American Society of Nephrology and Centers for Disease Control and Prevention Antibiotic Stewardship White Paper Writing Group.

Antibiotic use is necessary in the outpatient hemodialysis setting because patients receiving hemodialysis are at increased risk for infections and sepsis. However, inappropriate antibiotic use can lead to adverse drug events, including adverse drug reactions and infections with Clostridioides difficile and antibiotic-resistant bacteria. Optimizing antibiotic use can decrease adverse events and improve infection cure rates and patient outcomes. The American Society of Nephrology and the US Centers for Disease Control and Prevention created the Antibiotic Stewardship in Hemodialysis White Paper Writing Group, comprising experts in antibiotic stewardship, infectious diseases, nephrology, and public health, to highlight strategies that can improve antibiotic prescribing for patients receiving maintenance hemodialysis. Based on existing evidence and the unique patient and clinical setting characteristics, the following strategies for improving antibiotic use are reviewed: expanding infection and sepsis prevention activities, standardizing blood culture collection processes, treating methicillin-susceptible Staphylococcus aureus infections with ß-lactams, optimizing communication between nurses and prescribing providers, and improving data sharing across transitions of care. Collaboration among the Centers for Disease Control and Prevention; American Society of Nephrology; other professional societies such as infectious diseases, hospital medicine, and vascular surgery societies; and dialysis provider organizations can improve antibiotic use and the quality of care for patients receiving maintenance hemodialysis.

Implementation of the Core Elements of Antibiotic Stewardship in Nursing Homes Enrolled in the National Healthcare Safety Network.

In 2016, 42% of nursing homes enrolled in the National Healthcare Safety Network reported meeting all 7 of the Centers for Disease Control and Prevention's Core Elements of Antibiotic Stewardship. Bivariate analyses suggested that implementation of all core elements differed by ownership type and amount of infection prevention staff hours.

Characteristics of Hospitalized and Nonhospitalized Patients in a Nationwide Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, November 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). As of November 13, 2019, 49 states, the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands) have reported 2,172 EVALI cases to CDC, including 42 (1.9%) EVALI-associated deaths. To inform EVALI surveillance, including during the 2019-20 influenza season, case report information supplied by states for hospitalized and nonhospitalized patients with EVALI were analyzed using data collected as of November 5, 2019. Among 2,016 EVALI patients with available data on hospitalization status, 1,906 (95%) were hospitalized, and 110 (5%) were not hospitalized. Demographic characteristics of hospitalized and nonhospitalized patients were similar; most were male (68% of hospitalized versus 65% of nonhospitalized patients), and most were aged <35 years (78% of hospitalized versus 74% of nonhospitalized patients). These patients also reported similar use of tetrahydrocannabinol (THC)-containing products (83% of hospitalized versus 84% of nonhospitalized patients). Given the similarity between hospitalized and nonhospitalized EVALI patients, the potential for large numbers of respiratory infections during the emerging 2019-20 influenza season, and the potential difficulty in distinguishing EVALI from respiratory infections, CDC will no longer collect national data on nonhospitalized EVALI patients. Further collection of data on nonhospitalized patients will be at the discretion of individual state, local, and territorial health departments. Candidates for outpatient management of EVALI should have normal oxygen saturation (≥95% while breathing room air), no respiratory distress, no comorbidities that might compromise pulmonary reserve, reliable access to care, strong social support systems, and should be able to ensure follow-up within 24-48 hours of initial evaluation and to seek medical care promptly if respiratory symptoms worsen. Health care providers should emphasize the importance of annual influenza vaccination for all persons aged ≥6 months, including persons who use e-cigarette, or vaping, products (2,3).

Update: Interim Guidance for Health Care Providers for Managing Patients with Suspected E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, November 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). CDC has published recommendations for health care providers regarding EVALI (2-4). Recently, researchers from Utah and New York published proposed diagnosis and treatment algorithms for EVALI (5,6). EVALI remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment. Because patients with EVALI can experience symptoms similar to those associated with influenza or other respiratory infections (e.g., fever, cough, headache, myalgias, or fatigue), it might be difficult to differentiate EVALI from influenza or community-acquired pneumonia on initial assessment; EVALI might also co-occur with respiratory infections. This report summarizes recommendations for health care providers managing patients with suspected or known EVALI when respiratory infections such as influenza are more prevalent in the community than they have been in recent months (7). Recommendations include 1) asking patients with respiratory, gastrointestinal, or constitutional symptoms about the use of e-cigarette, or vaping, products; 2) evaluating those suspected to have EVALI with pulse oximetry and obtaining chest imaging, as clinically indicated; 3) considering outpatient management for clinically stable EVALI patients who meet certain criteria; 4) testing patients for influenza, particularly during influenza season, and administering antimicrobials, including antivirals, in accordance with established guidelines; 5) using caution when considering prescribing corticosteroids for outpatients, because this treatment modality has not been well studied among outpatients, and corticosteroids could worsen respiratory infections; 6) recommending evidence-based treatment strategies, including behavioral counseling, to help patients discontinue using e-cigarette, or vaping, products; and 7) emphasizing the importance of annual influenza vaccination for all persons aged ≥6 months, including patients who use e-cigarette, or vaping products.

Opportunities to Improve Fluoroquinolone Prescribing in the United States for Adult Ambulatory Care Visits.

The Food and Drug Administration warned against fluoroquinolone use for conditions with effective alternative agents. An estimated 5.1% of adult ambulatory fluoroquinolone prescriptions were for conditions that did not require antibiotics, and 19.9% were for conditions where fluoroquinolones are not recommended first-line therapy. Unnecessary fluoroquinolone use should be reduced.

The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial.

BACKGROUND: Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. METHODS: The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18-49 years, naive to the 2014-15 influenza vaccine, and did not have any significant dermatological disorders. Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 µg of haemagglutinin per H1N1 vaccine strain, 17 µg of haemagglutinin per H3N2 vaccine strain, and 15 µg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. A research pharmacist prepared the randomisation code using a computer-generated randomisation schedule with a block size of 4. Because of the nature of the study, participants were not masked to the type of vaccination method (ie, microneedle patch vs intramuscular injection). Primary safety outcome measures are the incidence of study product-related serious adverse events within 180 days, grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection site and systemic reactogenicity on the day of study product administration through 7 days after administration, and secondary safety outcomes are new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days, all analysed by intention to treat. Secondary immunogenicity outcomes are antibody titres at day 28 and percentages of seroconversion and seroprotection, all determined by haemagglutination inhibition antibody assay. The trial is completed and registered with ClinicalTrials.gov, number NCT02438423. FINDINGS: Between June 23, 2015, and Sept 25, 2015, 100 participants were enrolled and randomly assigned to a group. There were no treatment-related serious adverse events, no treatment-related unsolicited grade 3 or higher adverse events, and no new-onset chronic illnesses. Among vaccinated groups (vaccine via health-care worker administered microneedle patch or intramuscular injection, or self-administered microneedle patch), overall incidence of solicited adverse events (n=89 vs n=73 vs n=73) and unsolicited adverse events (n=18 vs n=12 vs n=14) were similar. Reactogenicity was mild, transient, and most commonly reported as tenderness (15 [60%] of 25 participants [95% CI 39-79]) and pain (11 [44%] of 25 [24-65]) after intramuscular injection; and as tenderness (33 [66%] of 50 [51-79]), erythema (20 [40%] of 50 [26-55]), and pruritus (41 [82%] of 50 [69-91]) after vaccination by microneedle patch application. The geometric mean titres were similar at day 28 between the microneedle patch administered by a health-care worker versus the intramuscular route for the H1N1 strain (1197 [95% CI 855-1675] vs 997 [703-1415]; p=0·5), the H3N2 strain (287 [192-430] vs 223 [160-312]; p=0·4), and the B strain (126 [86-184] vs 94 [73-122]; p=0·06). Similar geometric mean titres were reported in participants who self-administered the microneedle patch (all p>0·05). The seroconversion percentages were significantly higher at day 28 after microneedle patch vaccination compared with placebo (all p<0·0001) and were similar to intramuscular injection (all p>0·01). INTERPRETATION: Use of dissolvable microneedle patches for influenza vaccination was well tolerated and generated robust antibody responses. FUNDING: National Institutes of Health.

Emergency postexposure vaccination with vesicular stomatitis virus-vectored Ebola vaccine after needlestick.

IMPORTANCE: Safe and effective vaccines and drugs are needed for the prevention and treatment of Ebola virus disease, including following a potentially high-risk exposure such as a needlestick. OBJECTIVE: To assess response to postexposure vaccination in a health care worker who was exposed to the Ebola virus. DESIGN AND SETTING: Case report of a physician who experienced a needlestick while working in an Ebola treatment unit in Sierra Leone on September 26, 2014. Medical evacuation to the United States was rapidly initiated. Given the concern about potentially lethal Ebola virus disease, the patient was offered, and provided his consent for, postexposure vaccination with an experimental vaccine available through an emergency Investigational New Drug application. He was vaccinated on September 28, 2014. INTERVENTIONS: The vaccine used was VSVΔG-ZEBOV, a replicating, attenuated, recombinant vesicular stomatitis virus (serotype Indiana) whose surface glycoprotein gene was replaced by the Zaire Ebola virus glycoprotein gene. This vaccine has entered a clinical trial for the prevention of Ebola in West Africa. RESULTS: The vaccine was administered 43 hours after the needlestick occurred. Fever and moderate to severe symptoms developed 12 hours after vaccination and diminished over 3 to 4 days. The real-time reverse transcription polymerase chain reaction results were transiently positive for vesicular stomatitis virus nucleoprotein gene and Ebola virus glycoprotein gene (both included in the vaccine) but consistently negative for Ebola virus nucleoprotein gene (not in the vaccine). Early postvaccination cytokine secretion and T lymphocyte and plasmablast activation were detected. Subsequently, Ebola virus glycoprotein-specific antibodies and T cells became detectable, but antibodies against Ebola viral matrix protein 40 (not in the vaccine) were not detected. CONCLUSIONS AND RELEVANCE: It is unknown if VSVΔG-ZEBOV is safe or effective for postexposure vaccination in humans who have experienced a high-risk occupational exposure to the Ebola virus, such as a needlestick. In this patient, postexposure vaccination with VSVΔG-ZEBOV induced a self-limited febrile syndrome that was associated with transient detection of the recombinant vesicular stomatitis vaccine virus in blood. Strong innate and Ebola-specific adaptive immune responses were detected after vaccination. The clinical syndrome and laboratory evidence were consistent with vaccination response, and no evidence of Ebola virus infection was detected.

Mycobacterium paraffinicum causing symptomatic pulmonary infection.

Mycobacterium paraffinicum has been newly recognized as a species. A case of symptomatic pulmonary infection caused by M. paraffinicum is described, and as far as we know, this is the first case of the organism as a human pathogen.