The Cost of Developing and Implementing an Antepartum Referral Program for Penicillin Allergy Evaluation at a Single Academic Tertiary Care Hospital.

OBJECTIVE: Approximately 10% of pregnant individuals report a penicillin allergy, yet most are not truly allergic. Allergy verification during pregnancy is safe and recommended; however, many hospitals lack the infrastructure to execute testing. Our aim was to evaluate the cost of developing and implementing a penicillin allergy referral program for pregnant individuals at an academic institution and to compare costs of care between patients who were referred and not referred through the program. STUDY DESIGN: We conducted an economic analysis of our institution's antepartum penicillin allergy referral program. We prospectively collected detailed resource utilization data and conducted the analysis from the program's perspective, accounting for costs related to program development, allergy verification, antibiotic cost, and delivery hospitalization. Costs were compared between patients who were referred for evaluation versus patients who were not referred using bivariate tests as well as quantile regression adjusting for baseline differences. A sensitivity analysis was performed for allergy testing cost. All cost estimates were inflation adjusted to 2021 U.S. dollars. RESULTS: The startup cost of program development and educational initiatives was $19,920, or 86 per patient. The median allergy evaluation cost was $397 (interquartile range: $303-663). There was no significant difference in maternal (median: $13,579 vs. 13,999, p = 0.94) or neonatal (median: $3,565 vs. 3,577, p = 0.55) delivery hospitalization cost or antibiotic cost (median: $1.57 vs. 3.87, p = 0.10) between referred and nonreferred patients. Overall, the total cost per person did not differ significantly between study groups (median: $18,931 vs. 18,314, p = 0.69). CONCLUSION: The cost of developing a penicillin allergy referral program in pregnancy was modest and did not significantly alter short-term cost of care with potential for long-term cost benefit. Verification of a reported penicillin allergy is an integral part of antibiotic stewardship, and the pregnancy period should be utilized as an important opportunity to perform this evaluation. KEY POINTS: · The cost of developing and implementing an antepartum penicillin allergy referral program is modest.. · Program cost did not significantly alter short-term cost with a potential for long-term cost benefit.. · Penicillin allergy verification is an important part of antibiotic stewardship and should be expanded..

Costs and cost-effectiveness of management of possible serious bacterial infections in young infants in outpatient settings when referral to a hospital was not possible: Results from randomized trials in Africa.

INTRODUCTION: Serious bacterial neonatal infections are a major cause of global neonatal mortality. While hospitalized treatment is recommended, families cannot access inpatient treatment in low resource settings. Two parallel randomized control trials were conducted at five sites in three countries (Democratic Republic of Congo, Kenya, and Nigeria) to compare the effectiveness of treatment with experimental regimens requiring fewer injections with a reference regimen A (injection gentamicin plus injection procaine penicillin both once daily for 7 days) on the outpatient basis provided to young infants (0-59 days) with signs of possible serious bacterial infection (PSBI) when the referral was not feasible. Costs were estimated to quantify the financial implications of scaleup, and cost-effectiveness of these regimens. METHODS: Direct economic costs (including personnel, drugs and consumable costs) were estimated for identification, prenatal and postnatal visits, assessment, classification, treatment and follow-up. Data on time spent by providers on each activity was collected from 83% of providers. Indirect marginal financial costs were estimated for non-consumables/capital, training, transport, communication, administration and supervision by considering only a share of the total research and health system costs considered important for the program. Total economic costs (direct plus indirect) per young infant treated were estimated based on 39% of young infants enrolled in the trial during 2012 and the number of days each treated during one year. The incremental cost-effectiveness ratio was calculated using treatment failure after one week as the outcome indicator. Experimental regimens were compared to the reference regimen and pairwise comparisons were also made. RESULTS: The average costs of treating a young infant with clinical severe infection (a sub-category of PSBI) in 2012 was lowest with regimen D (injection gentamicin once daily for 2 days plus oral amoxicillin twice daily for 7 days) at US$ 20.9 (95% CI US$ 16.4-25.3) or US$ 32.5 (2018 prices). While all experimental regimens B (injection gentamicin once daily plus oral amoxicillin twice daily, both for 7 days), regimen C (once daily of injection gentamicin injection plus injection procaine penicillin for 2 days, thereafter oral amoxicillin twice daily for 5 days) and regimen D were found to be more cost-effective as compared with the reference regimen A; pairwise comparison showed regimen D was more cost-effective than B or C. For fast breathing, the average cost of treatment with regimen E (oral amoxicillin twice daily for 7 days) at US$ 18.3 (95% CI US$ 13.4-23.3) or US$ 29.0 (2018 prices) was more cost-effective than regimen A. Indirect costs were 32% of the total treatment costs. CONCLUSION: Scaling up of outpatient treatment for PSBI when the referral is not feasible with fewer injections and oral antibiotics is cost-effective for young infants and can lead to increased access to treatment resulting in potential reductions in neonatal mortality. CLINICAL TRIAL REGISTRATION: The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

A Comprehensive Prospective Study of the Costs Associated With Evaluation of beta-Lactam Allergy

BACKGROUND: Being labeled as allergic to penicillin (unverified beta-lactam allergy) can result in patients receiving broader-spectrum antibiotics than necessary that may be more toxic, less effective, and/or more expensive than alternative options. OBJECTIVE: We aimed to evaluate the real costs of evaluating beta-lactam allergy. METHODS: We performed a prospective real-life observational study designed to evaluate all adult patients who consulted for suspected beta-lactam allergy over a 1-year period. Direct and indirect costs were systematically recorded. Direct health costs were calculated based on the number of visits and all additional and diagnostic tests performed, direct nonhealth costs based on the number of visits and the distance from their homes to the Allergy Department, and indirect costs based on absenteeism. RESULTS: A total of 296 patients with suspected allergy to beta-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct health care costs were (Euro)28 176.70, with a mean (SD) cost of (Euro)95.19 (37.20). Direct nonhealth costs reached (Euro)6551.73, that is, (Euro)22.13 (40.44) per patient. Indirect health costs reached (Euro)20 769.20, with a mean of (Euro)70.17 (127.40). In summary, the total cost was (Euro)55 497.63, that is, a cost per patient of (Euro)187.49 (148.14). CONCLUSIONS: When all possible costs are taken into account, the evaluation of beta-lactam allergy is not expensive and can reduce future expense arising from unnecessary use of more expensive and less effective antibiotics

INTRODUCCIÓN: Un diagnóstico no verificado de alergia a la penicilina o a los betalactámicos (BL) conlleva que los pacientes reciban antibióticos de amplio espectro, que pueden ser más tóxicos, menos efectivos, y/o de mayor coste. OBJETIVO: Evaluar los costes reales de un estudio de alergia a los betalactámicos. MÉTODOS: Se diseñó un estudio observacional prospectivo en condiciones de práctica clínica habitual en el que se evaluaron todos los pacientes adultos que consultaron por sospecha de alergia a BL durante un año. Los costes directos e indirectos se recogieron sistemáticamente. Los costes directos sanitarios se calcularon teniendo en cuenta el número de visitas y todas las pruebas diagnósticas realizadas; en los costes directos no sanitarios se consideraron el número de visitas y los kilómetros desde el domicilio hasta el Servicio de Alergología; en los costes indirectos se evaluó el absentismo. RESULTADOS: Se evaluaron 296 pacientes remitidos desde el 1 de junio de 2017 hasta el 31 de mayo de 2018. Los costes directos totales sanitarios fueron 28.176,70 (Euro): coste medio (desviación estándar, DS) de 95,19 (Euro) (37,20). Los costes directos no sanitarios alcanzaron, 6.551,73: coste medio 22,13 (40,44). Los costes indirectos fueron 20.769,20 (Euro): coste medio (DS) 70,17 (127,40). En resumen, la cantidad total fue de 55.497,63 (Euro), lo que supone un coste medio de 187,49 (Euro) (148,14). CONCLUSIONES: Considerando todos los costes posibles, la evaluación de la alergia a betalactámicos no es cara y puede ahorrar gastos futuros debido a una utilización innecesaria de antibióticos más caros y menos efectivos

High-cost, high-need patients: the impact of reported penicillin allergy.

OBJECTIVES: More than 90% of patients who report a penicillin allergy have the allergy disproved when tested. Unnecessary use of alternative (non-beta-lactam) antibiotics can result in more treatment failures and adverse reactions. We described the prevalence and impact of a reported penicillin allergy in high-cost, high-need (HCHN) patients. STUDY DESIGN: Retrospective cohort. METHODS: We identified HCHN patients in a care management program of an urban academic medical center (January 1, 2014, to December 31, 2016). We used multivariable logistic regression models to determine the association between a reported penicillin allergy and antibiotic use. We used multivariable Poisson regression models to determine the association between a reported penicillin allergy, with or without multiple drug intolerance syndrome (MDIS; ≥3 reported drug allergies), and healthcare resource utilization (HRU). RESULTS: Of 1870 HCHN patients, 383 (20%) reported penicillin allergy, 835 (45%) had MDIS, and 290 (16%) had both. HCHN patients reporting penicillin allergy had an increased odds of beta-lactam alternative antibiotic use (adjusted odds ratio, 3.84; 95% CI, 2.17-6.80). HRU was significantly higher for patients reporting a penicillin allergy alone (adjusted relative risk [aRR], 1.13; 95% CI, 1.03-1.25) and with concurrent MDIS (aRR, 1.20; 95% CI, 1.08-1.34). CONCLUSIONS: HCHN patients had a high burden of reported drug allergy. A reported penicillin allergy conferred a 4-fold increased odds of beta-lactam alternative antibiotic use. Reporting penicillin allergy, with and without MDIS, was associated with significantly more HRU. HCHN care management programs should consider systematic drug allergy evaluations to optimize antibiotic use in these fragile patients.

The Costs of Drugs in Infectious Diseases: Branded, Generics, and Why We Should Care.

While health care providers have largely turned a blind eye, the cost of health care in the US has been skyrocketing, in part as a result of rising drug prices. Patent protections and market exclusivity, while serving to incentivize targeted new drug development, have exacerbated inequitable outcomes and reduced access, sometimes fueling national epidemics. Branded drug manufacturers face few barriers to exorbitant pricing of drugs with exclusivity-as in the cases of Sovaldi, Zyvox, and Truvada. Furthermore, albendazole, pyrimethamine, and penicillin demonstrate that generic medications without patent exclusivity are not guaranteed to have durably low costs, especially where manufacturer competition is lacking. There is a way forward: through education and awareness, cost-conscious guideline development, government regulation, and market-level incentives, health care providers can collaborate to contain drug prices, curbing expenditures overall while expanding health care access to patients.

Penicillin allergy skin testing as an antibiotic stewardship intervention reduces alternative antibiotic exposures in hematopoietic stem cell transplant recipients.

BACKGROUND: Antibiotic allergy de-labeling using penicillin allergy skin testing (PAST) can reduce the use and cost of alternative, non-ß-lactam antibiotics in general inpatient populations. This strategy's role in hematopoietic stem cell transplant (HSCT) recipients is unclear. METHODS: This study aimed to determine the effect of a pre-transplant PAST protocol on antibiotic use, days of therapy (DOT), and cost in an immunocompromised population at a single center from 7/1/2010-2/1/2019. Patients who received chimeric antigen receptor (CAR) T-cell therapy and those who underwent transplantation in the outpatient setting were excluded. RESULTS: Of 1560 patients who underwent inpatient HSCT during the study period, 208 reported ß-lactam allergy (136/844 [16%] pre- and 72/716 [10%] post-implementation; P < .001). PAST was performed on 7% and 54% of HSCT recipients pre- and post-implementation, respectively. Only two positive PAST were noted. There were no adverse reactions to PAST. There were no significant differences in the disease and transplant characteristics between the two groups. Days of therapy and cost of alternative antibiotics significantly decreased post-implementation (mean 788 vs 627 days, P = .01; mean $24 425 vs $17 518, P = .009). CONCLUSION: Penicillin allergy skin testing adjudicates reported ß-lactam allergy in HSCT recipients, lowering use, DOT, and cost of alternative antibiotics and promoting effective formulary agents to treat immunocompromised HSCT recipients.

Cost and Risk Analysis of Lifelong Penicillin Allergy.

Patients labeled as being penicillin-allergic require the use of alternative antibiotics. The objective of this study was to estimate the lifetime antibiotic costs of patients labeled as being penicillin allergic prior to age 10 compared with those who were not penicillin allergic and to compare antibiotic utilization between these 2 groups with regard to risks of adverse effects. Using the low end of the antibiotic cost range, penicillin-allergic patients had a mean lifetime antibiotic cost of $8171 per patient, compared with $6278 for non-penicillin-allergic patients, a difference of $1893. Penicillin-allergic patients utilized more moderate-spectrum antibiotics, more fluoroquinolones, and had a higher estimated Clostridium difficile risk.

Antibiotic allergy labels-the impact of taking a clinical history.

BACKGROUND: Many patients admitted to hospital have an antibiotic allergy (AAL) documented in their medical record. In many of these, the reaction is not a hypersensitivity reaction or may no longer be relevant. Despite this, the label adversely affects patient care directly in terms of antibiotic selection, and indirectly in terms of patient costs and the development of antimicrobial resistance. AIMS: To estimate the prevalence of AALs in a cohort of hospitalised patients, to investigate the feasibility of de-labelling through re-challenge based solely upon clinical grounds. DESIGN: This is a cross-sectional study conducted over a 6-month period on adult inpatients. An allergy history was taken from each patient and compared with medical record data regarding allergy. Antibiotic selection data were collected (if relevant). It was then determined whether immediate de-labelling was appropriate, if direct provocation test (DPT) could be relatively safely performed, and if antibiotic selection was appropriate. RESULTS: Three thousand eight hundred and fifty five patients were screened, 553 (14.35%) had an AAL, and 352 were interviewed. There were 426 AALs; 276 (64.8%) towards a penicillin. After taking a detailed clinical history of the type of reaction, approximately 20% could be immediately de-labelled and educated (non-allergic, non-severe reactions) and another 38% with either a definite or vague history of mild cutaneous reaction would be suitable for an attempt at clinical de-labelling DPT. CONCLUSIONS: These simple measures to 'de-label' patients appropriately, would increase the quality of care of this group known to have higher costs, infection with more resistant bacteria and worse health outcomes that 'non-labelled' patients.

Clinical outcomes following inpatient penicillin allergy testing: A systematic review and meta-analysis.

BACKGROUND: A documented penicillin allergy is associated with increased morbidity including length of hospital stay and an increased incidence of resistant infections attributed to use of broader-spectrum antibiotics. The aim of the systematic review was to identify whether inpatient penicillin allergy testing affected clinical outcomes during hospitalization. METHODS: We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library over the past 20 years. Inpatients having a documented penicillin allergy that underwent penicillin allergy testing were included. RESULTS: Twenty-four studies met eligibility criteria. Study sample size was between 24 and 252 patients in exclusively inpatient cohorts. Penicillin skin testing (PST) with or without oral amoxicillin challenge was the main intervention described (18 studies). The population-weighted mean for a negative PST was 95.1% [CI 93.8-96.1]. Inpatient penicillin allergy testing led to a change in antibiotic selection that was greater in the intensive care unit (77.97% [CI 72.0-83.1] vs 54.73% [CI 51.2-58.2], P<.01). An increased prescription of penicillin (range 9.9%-49%) and cephalosporin (range 10.7%-48%) antibiotics was reported. Vancomycin and fluoroquinolone use was decreased. Inpatient penicillin allergy testing was associated with decreased healthcare cost in four studies. CONCLUSIONS: Inpatient penicillin allergy testing is safe and effective in ruling out penicillin allergy. The rate of negative tests is comparable to outpatient and perioperative data. Patients with a documented penicillin allergy who require penicillin should be tested during hospitalization given its benefit for individual patient outcomes and antibiotic stewardship.

Penicillin skin testing as an antimicrobial stewardship initiative.

PURPOSE: An initiative to determine the effects of penicillin skin testing (PST) from an antimicrobial stewardship perspective is described. SUMMARY: Penicillin allergy is one of the most frequently reported allergies; however, only about 10% of self-reports of penicillin allergy are accurate. Incorrect penicillin allergies are therefore a significant barrier to antimicrobial stewardship, with important clinical and economic implications, including increased antimicrobial resistance, an increased overall cost of care, increased length of stay, and, ultimately, increased mortality. As part of its antimicrobial stewardship program, a community health system launched a PST initiative in order to optimize therapy, reduce adverse events acquisition costs, and minimize development of antibiotic resistance. The PST program involves the use of a standardized protocol for the assessment of hypersensitivity to penicillin in patients with suspected penicillin allergy. Among 36 patients who completed the PST protocol during an eight-month period, all had a negative result; in 27 of those patients, a conversion of antimicrobial therapy to a penicillin or cephalosporin was implemented as a direct result of PST. CONCLUSION: In patients with a self-reported penicillin allergy, PST led to a reduction in the use of carbapenems, aztreonam, vancomycin, and other broad-spectrum agents within a health system. A decrease in drug costs was documented in a sample of patients switched to a penicillin or a cephalosporin after PST.

[Penicillin production in Chile between 1944 and 1954]. / Producción de Penicilina en Chile entre 1944 y 1954.

Penicillin production in Chile was a pioneering development; however there is not much information to learn about it. The Chilean Institute for Bacteriology (Instituto Bacteriológico de Chile) produced penicillin between 1944 and 1973. The stage starting in 1953 is better known since there was an agreement with United Nations. Our research focused on building a story about production between 1944 and 1954 based on archival information and the national and international historic context. Our results place Chile amongst the pioneer countries in the successful industrialization of the drug. Our conclusions are that this was a proper industrial production as opposite to a pilot plant - a name commonly used to call the early factory. We explain the production plant trajectory by making relations between technological change and governance. Finally, we believe the later expansion of the plant, in the context of the agreement with the United Nations, took place under unpromising governance conditions, which called for passive innovation and technology management.

A real-time prospective evaluation of clinical pharmaco-economic impact of diagnostic label of 'penicillin allergy' in a UK teaching hospital.

AIMS: To perform a pharmaco-economic analysis of prescribing alternative antibiotics in patients with a diagnostic label of 'penicillin allergy' and assess whether collation of information from a structured history and liaison with the family physician could reduce costs. METHODS: A prospective pro-forma-based interview of randomly selected in-patients and their family physician was used to assess the validity of the diagnostic label of 'penicillin allergy'. Cost analysis of prescription of alternative antibiotics was performed and compared with first-line agents. RESULTS: 102 patients were assessed and only 40% (n=41) were found to have a history consistent with penicillin hypersensitivity, 40% (n=41) were likely 'not allergic' and 20% (n=20) had 'indeterminate' reactions. Total cost of antibiotics prescribed for patients with penicillin allergy was 1.82-2.58-fold higher than for first-line antibiotics. CONCLUSIONS: Obtaining a structured history from the patient and family physician alone can enable an accurate identification of penicillin allergy status. Total acquisition cost of second-line antibiotics is higher than if these patients were prescribed first-line antibiotics.

The long postwar and the politics of penicillin: early circulation and smuggling in Spain, 1944-1954.

In this paper I explore the early circulation of penicillin. I review the early distribution in Spain of a scarce product, reflect on the available sources about the illegal penicillin trade and discuss some cases of smuggling. I argue the early distribution of penicillin involved time and geography, a particular chronology of post Second World War geopolitics. Penicillin practices and experiences belong to this period, in a dictatorship that tolerated smuggling and illegal trade of other products, some, like penicillin, produced in neighbouring countries. As a commodity that crossed borders, penicillin, transiting between the law and hidden trade, between countries and social domains--between war fronts and from a war front to an urban site to be sold--reveals practices of the early years of prosperity in the 1950s. These transits were permanent tests of a society based on taxes and exchanges, law and bureaucracy, control, discipline and the creation of standards.

The fabbrica della penicillina in postwar Italy: an institutionalist approach.

This paper focuses on the motives and long-term effects of the momentous decision to build a world-class biomedical research laboratory, the International Center for Chemical Microbiology, at the Istituto Superiore di Sanità in Rome, rather than develop domestic production of penicillin to meet the needs of a destitute postwar Italy. An institutionalist approach will provide a richer vision of the intersections of scientific and national political history in postwar Italy and the Cold War. The Center failed in its modernising mission due to an insular mentality producing an 'enclosure effect' against the State, the healthcare system and the pharmaceutical industry. The absence of a scientific base together with an economic policy of 'liberal protectionism' that placed premiums on import tariffs and the licensing of foreign products explains the path dependency of the pharmaceutical industry during the postwar years and its demise in the 1960s.

Primary prevention of acute rheumatic fever and rheumatic heart disease with penicillin in South African children with pharyngitis: a cost-effectiveness analysis.

BACKGROUND: Acute rheumatic fever and subsequent rheumatic heart disease remain significant in developing countries. We describe a cost-effective analysis of 7 strategies for the primary prevention of acute rheumatic fever and rheumatic heart disease in children presenting with pharyngitis in urban primary care clinics in South Africa. METHODS AND RESULTS: We used a Markov model to assess the cost-effectiveness of treatment with intramuscular penicillin using each of the following strategies: (1) empirical (treat all); (2) positive throat culture (culture all); (3) clinical decision rule (CDR) score ≥2 (CDR 2+); (4) CDR score ≥3 (CDR 3+); (5) treating those with a CDR score ≥2 plus those with CDR score <2 and positive cultures (CDR 2+, culture CDR negatives); (6) treating those with a CDR score ≥3 plus those with CDR score <3 and positive cultures (CDR 3+, culture CDR negatives); and (7) treat none. The strategies ranked in order from lowest cost were treat all ($11.19 per child), CDR 2+ ($11.20); the CDR 3+ ($13.00); CDR 2+, culture CDR negatives ($16.42); CDR 3+, culture CDR negatives ($23.89); and culture all ($27.21). The CDR 2+ is the preferred strategy at less than $150/quality-adjusted life year compared with the treat all strategy. A strategy of culturing all children compared with the CDR 2+ strategy costs more than $125 000/quality-adjusted life year gained. CONCLUSIONS: Treating all children presenting with pharyngitis in urban primary care clinics in South Africa with intramuscular penicillin is the least costly. A strategy of using a clinical decision rule without culturing is overall the preferred strategy. A strategy of culturing all children may be prohibitively expensive.

Treatment of patients with a history of penicillin allergy in a large tertiary-care academic hospital.

BACKGROUND: Prescribing antibiotics to patients with a history of penicillin allergy is common in clinical practice. Opting for non-beta-lactam antibiotics has its inconveniences and is often unnecessary, because most of these patients are in fact not allergic. OBJECTIVE: This study aimed to determine how physicians in a large Canadian tertiary-care academic hospital without allergists on staff treat patients with a history of penicillin allergy. METHODS: A retrospective study was conducted during a 1-year period among all patients hospitalized in the intensive care unit, coronary care unit, and internal medicine wards. Files of patients with a record of penicillin allergy were reviewed to assess the need for antibiotics during their hospitalization and the decision-making process underlying the choice of antibiotic. The additional costs of alternative antibiotics were calculated. RESULTS: The files of 1738 patients admitted over a 1-year period were hand reviewed. A history of penicillin allergy was found in 172 patients (9.9%). The allergic reaction was described in only 30% of cases and left unmentioned in 20.7%. Beta-lactam antibiotics were used on 56 occasions despite a history of penicillin allergy. The use of alternative antibiotics in place of the beta-lactam standard of care carried an additional cost of $15,672 Canadian. CONCLUSION: Alleged penicillin allergy is common among hospitalized patients and leads to substantial additional costs. Poor documentation of penicillin allergy likely reflects a lack of knowledge on this issue in the medical community, which impairs optimal treatment of these patients. Increased education on this matter is needed, and allergists on staff could be part of the solution.

On the demand for prescription drugs: heterogeneity in price responses.

This paper estimates the price elasticity of demand for prescription drugs using an exogenous shift in consumer co-payment caused by a reform in the Danish subsidy scheme for the general public. Using purchasing records for the entire Danish population, I show that the average price response for the most commonly used drug yields demand elasticities in the range of -0.36 to -0.5. The reform is shown to affect women, the elderly, and immigrants the most. Furthermore, this paper shows significant heterogeneity in the price response over different types of antibiotics, suggesting that the price elasticity of demand varies considerably even across relatively similar drugs.