Impact of Pseudomonas aeruginosa on resource utilization and costs in patients with exacerbated non-cystic fibrosis bronchiectasis.

AIMS: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic progressive respiratory disorder occurring at a rate ranging from 4.2 to 278.1 cases per 100,000 persons, depending on age, in the United States. For many patients with NCFB, the presence of Pseudomonas aeruginosa (PA) makes treatment more complicated and typically has worse outcomes. Management of NCFB can be challenging, warranting a better understanding of the burden of illness for NCFB, treatments applied, healthcare resources used, and subsequent treatment costs. Comparing patients diagnosed with exacerbated NCFB, with or without PA on antibiotic utilization, treatments, and healthcare resources utilization and costs was the purpose of this study. MATERIALS AND METHODS: This was a retrospective cohort study of commercial claims from IQVIA's PharMetrics Plus database (January 1,2006-December 31, 2020). Study patients with a diagnosis of NCFB were stratified into two groups based on the presence or absence of PA, then followed to identify demographic characteristics, comorbid conditions, antibiotic treatment regimen prescribed, healthcare resources utilized, and costs of care. RESULTS: The results showed that patients with exacerbated NCFB who were PA+ had significantly more oral antibiotic fills per patient per year, more inpatient admissions with a longer length of stay, and more outpatient encounters than those who were PA-. For costs, PA+ patients also had significantly greater total healthcare costs per patient when compared to those who were PA-. CONCLUSION: Exacerbated NCFB with PA+ was associated with increased antibiotic usage, greater resource utilization, and increased costs. The major contributor to the cost differences was the use of inpatient services. Treatment strategies aimed at reducing the need for inpatient treatment could lessen the disparities observed in patients with NCFB.

A quality improvement intervention on surgical prophylaxis impact in antibiotic consumption and cost in selected surgical procedures.

BACKGROUND: Improper compliance with antibiotic prophylaxis (AP) in surgery is associated with an increased risk of surgical site infection (SSI), and impacts the efficiency of healthcare. OBJECTIVE: Evaluate the impact of an intervention in compliance with AP in selected surgical procedures and its effect on antibiotic consumption and cost. METHODS: A prospective interventional study was performed in a community hospital from January to December 2022. The baseline period was considered January-April 2022 and the intervention period May-December 2022. All patients who underwent cesarean section, appendectomies, hernia surgery, open reduction and internal fixation (ORIF), abdominoplasty, and cholecystectomy during the study period were selected. The intervention includes staff education, pharmacy interventions, monitoring the quality of prescriptions and feedback, and improved role of anesthesia staff, and department champions. RESULTS: The study involved 192 and 617 surgical procedures in the baseline and intervention periods respectively. The compliance with timing, selection, dose, and discontinuation achieved 100%, 99.2%, and 97.6% from baseline figures of 92.7%, 95.8%, and 81.3%, respectively. The antibiotic consumption was reduced by 55.1% during the intervention with a higher contribution of other antibiotics (94.1% reduction) in comparison with antibiotics as per policy (31.2% reduction). The cost was reduced by 47.2% (antibiotic as per policy 31.9%, other antibiotics 94.2%). CONCLUSION: The implemented strategy was effective in improving the quality of antibiotic prophylaxis with a significant impact in reducing antibiotic consumption and cost.

Economic evaluation: immunoglobulin vs prophylactic antibiotics in hypogammaglobulinemia and hematological malignancies.

ABSTRACT: Patients with hematological malignancies are at high risk of developing hypogammaglobulinemia (HGG) and infections. Immunoglobulin (Ig) is one recommended option to prevent these infections, but it is expensive, and its cost-effectiveness compared with other prevention strategies remains unknown. We conducted a trial-based economic evaluation from the Australian health care system perspective to estimate the 12-month cost-effectiveness of prophylactic Ig vs prophylactic antibiotics in 63 adults with HGG and hematological malignancies participating in the RATIONAL feasibility trial. Two analyses were conducted: (1) cost-utility analysis to assess the incremental cost per quality-adjusted life year (QALY) gained; and (2) cost-effectiveness analysis to assess the incremental cost per serious infection prevented (grade ≥3) and per any infection (any grade) prevented. Over 12 months, the total cost per patient was significantly higher in the Ig group than in the antibiotic group (mean difference, AU$29 140; P < .001). Most patients received IVIg, which was the main cost driver; only 2 patients in the intervention arm received subcutaneous Ig. There were nonsignificant differences in health outcomes. Results showed Ig was more costly than antibiotics and associated with fewer QALYs. The incremental cost-effectiveness ratio of Ig vs antibiotics was AU$111 262 per serious infection prevented, but Ig was more costly and associated with more infections when all infections were included. On average and for this patient population, Ig prophylaxis may not be cost-effective compared with prophylactic antibiotics. Further research is needed to confirm these findings in a larger population and considering longer-term outcomes. The trial was registered at the Australian and New Zealand Clinical Trials Registry as #ACTRN12616001723471.

Finding value in novel antibiotics: How can infectious diseases adopt incremental cost-effectiveness to improve new antibiotic utilization?

Research and development of innovative antimicrobials is paramount to addressing the antimicrobial resistance threat. Although antimicrobial discovery and development has increased, difficulties have emerged in the pharmaceutical industry after market approval. In this minireview, we summarize clinical trial data on recently approved antibiotics, calculate incremental cost-effectiveness ratio (ICER) values, and explore ways to adapt ICER calculations to the limitations of antimicrobial clinical trial design. We provide a systematic review and analysis of randomized, controlled studies of antibiotics approved from 2014 - 2022 and extracted the relevant clinical data. Adapted-ICER (aICER) calculations were conducted using the primary condition-specific outcome that was reported in each study (percent mortality or percent cure rate). The literature search identified 18 studies for the 8 total antibiotics which met inclusion criteria and contained data required for aICER calculation. aICER values ranged from -$17,374 to $4,966 per percent mortality and -$43,931 to $2,529 per percent cure rate. With regards to mortality, ceftolozane/tazobactam and imipenem/cilastatin/relebactam proved cost efficacious, with aICER values of $4,965 per percent mortality and $1,955 per percent mortality respectively. Finding value in novel antibiotic agents is imperative to further justifying their development, and aICER values are the most common method of determining value in healthcare. The current outcomes of clinical trials are difficult to translate to aICER, which most effectively use Quality-Adjusted Life Years (QALY) as the quality standard in other fields such as oncology. Future antimicrobial trials should consider introducing methods of assessing measures of health gain such as QALY to better translate the value of novel antimicrobials in healthcare.

Long-term effects of the global budget program and periodic price adjustment on antibacterial agents: A nationwide decomposition analysis between 2001 and 2016.

BACKGROUND: Previous studies have shown that financial strategies are beneficial for improving the appropriate use of antibiotics within a limited period of time. Long-term effects have rarely been explored. METHODS: This study evaluated the changes in expenditure and prescription patterns of antibacterial agents under the global budget (GB) program and drug price adjustment of a National Health Insurance scheme. Two structural methods, that is, the Laspeyres method and Fisher's Ideal Index decomposition method, were used to illustrate the impacts of price, volume, and drug change. RESULTS: During the first 5 years of the GB program (ie, 2001-2006), the expenses of antibacterial agents increased by 54.1%, while the volume decreased by 11% to 21.3%. Therapeutic choice was the predominant cause of expense growth. In the second and third 5-year periods (ie, 2006-2011 and 2011-2016), the driving force of therapeutic choice gradually decreased. The antibacterial expense remained stable with a slight increase in prescription volume. Periodic price adjustment contributed steadily to cost containment, by 21.9% to 39.9%. CONCLUSIONS: The GB program led to a remarkable increase in antibacterial expenses mainly attributed to therapeutic choice, especially in the early stage. In contrast, periodic price adjustment, provided steady benefits to pharmaceutical budget control without a noticeable increase in drug volume.

Direct Hospital Costs per Case of Periprosthetic Hip and Knee Joint Infections in Europe - A Systematic Review.

BACKGROUND: The rise of periprosthetic joint infections (PJIs) due to aging populations is steadily increasing the number of arthroplasties and treatment costs. This study analyzed the direct health care costs of PJI for total hip arthroplasty and total knee arthroplasty (TKA) in Europe. METHODS: The databases PubMed, Scopus, Embase, Cochrane, and Google Scholar were systematically screened for direct costs of PJI in Europe. Publications that defined the joint site and the procedure performed were further analyzed. Mean direct health care costs were calculated for debridement, antibiotics, and implant retention (DAIR), one-stage, and 2-stage revisions for hip and knee PJI, respectively. Costs were adjusted for inflation rates and reported in US-Dollar (USD). RESULTS: Of 1,374 eligible publications, 12 manuscripts were included in the final analysis after an abstract and full-text review. Mean direct costs of $32,933 were identified for all types of revision procedures for knee PJI. The mean direct treatment cost including DAIR for TKA after PJI was $19,476. For 2-stage revisions of TKA, the mean total cost was $37,980. For all types of hip PJI procedures, mean direct hospital costs were $28,904. For hip DAIR, one-stage and 2-stage treatment average costs of $7,120, $44,594, and $42,166 were identified, respectively. CONCLUSIONS: Periprosthetic joint infections are associated with substantial direct health care costs. As detailed reports on the cost of PJI are scarce and of limited quality, more detailed financial data on the cost of PJI treatment are urgently required.

A retrospective multicentre study on dalbavancin effectiveness and cost-evaluation in sternotomic wound infection treatment: DALBA SWIT Study.

OBJECTIVE: To evaluate the cost-effectiveness of dalbavancin compared with standard of care (SoC) treatment as daptomycin or teicoplanin in patients with sternal wound infections (SWI). METHODS: Multicentre retrospective study of patients diagnosed with SWI from January 2016 to December 2019 at two cardiac surgery facilities treated with dalbavancin, teicoplanin or daptomycin. Patients with SWI treated with dalbavancin were compared with SoC to evaluate resolution of infection at 90 and 180 days from infection diagnosis, length of stay (LoS) and management costs. RESULTS: 48 patients with SWI were enrolled, 25 (50%) male, median age 67 (60-73) years, Charlson index score 5 (4-7). Fifteen patients were treated with dalbavancin (31%) and 33 with SoC (69%): teicoplanin in 21 (63%), and daptomycin in 12 (37%). Staphylococcus species were the most frequent isolates (44, 92%), mostly (84%) resistant to methicillin. All patients were treated with surgical debridement followed by negative pressure wound therapy. Wound healing at day 90 and 180 was achieved in 46 (95.8%) and 34 (82.9%) of patients, respectively. A shorter length of hospitalization in patients treated with dalbavancin compared with SoC [12 (7-18) days vs 22 (12-36) days, p:0.009] was found. Treatment with dalbavancin resulted in total cost savings of €16 026 (95% CI 5976-26 076, P < 0.001). Savings were mainly related to the LoS that was significantly shorter in the dalbavancin group, generating significantly lower cost compared to SoC group. CONCLUSION: Dalbavancin treatment of sternal wound infections is effective and seems to reduce hospitalization length, leading to significantly lower costs.

Patient-reported outcome and cost implication of acute salvage of infected implant-based breast reconstruction with negative pressure wound therapy with Instillation (NPWTi) compared to standard care.

INTRODUCTION: Implant loss due to infection is the most devastating complication of implant-based breast reconstruction. The use of negative pressure wound therapy with instillation(NPWTi) for salvage of infected implant-based breast reconstructions has shown promising results allowing early reinsertion of a new implant as an alternative to the current management with delayed reinsertion. This study compares the patient-reported outcome and cost implication of NPWTi to the current management. METHODS: Twenty cases of infected breast implants treated with NPWTi(V.A.C. VERAFLO™ Therapy), followed by early reinsertion of new implants were compared to 20 cases that had delayed reinsertion(non-NPWTi). Patient satisfaction was evaluated using the BREAST-Q questionnaire. The average cost per patient was calculated using total operative expense, cost of inpatient stay, investigations, antibiotics, and outpatient visits. RESULTS: Treatment with NPWTi allowed earlier reinsertion of a new implant (NPWTi: 10.3 ± 2.77days vs. non-NPWTi: 247.45±111.28days, p<0.001). Patients in the NPWTi group reported higher satisfaction. The average cost per patient for NPWTi and non-NPWTi was £14,343.13±£2,786.70 and £8,920.31±£3,005.73, respectively(p<0.001). All patients treated with NPWTi had one admission and spent 11.9 ± 4.1days as inpatients, while non-NPWTi patients had 2.1 ± 0.3 admissions(p<0.001) and spent 7.1 ± 5.8days(p<0.004) as inpatients. Patients treated with NPWTi had more procedures (NPWTi:3.35±0.81 Vs. non-NPWTi:2.2 ± 0.41, p = 0.006); however, three non-NPWTi cases required flap reconstruction. CONCLUSION: Patients treated with NPWTi reported higher satisfaction, received a new and earlier implant, and had fewer admissions and outpatient visits; however, they incurred higher average costs, longer inpatient stays, and underwent more procedures. Early implant reinsertion preserves skin envelope; hence avoiding additional cost and stress related to further major autologous reconstruction.

Wound infection following implant removal of foot, ankle, lower leg or patella; a protocol for a multicenter randomized controlled trial investigating the (cost-)effectiveness of 2 g of prophylactic cefazolin compared to placebo (WIFI-2 trial).

BACKGROUND: Elective implant removal (IR) after fracture fixation is one of the most common procedures within (orthopedic) trauma surgery. The rate of surgical site infections (SSIs) in this procedure is quite high, especially below the level of the knee. Antibiotic prophylaxis is not routinely prescribed, even though it has proved to lower SSI rates in other (orthopedic) trauma surgical procedures. The primary objective is to study the effectiveness of a single intravenous dose of 2 g of cefazolin on SSIs after IR following fixation of foot, ankle and/or lower leg fractures. METHODS: This is a multicenter, double-blind placebo controlled trial with a superiority design, including adult patients undergoing elective implant removal after fixation of a fracture of foot, ankle, lower leg or patella. Exclusion criteria are: an active infection, current antibiotic treatment, or a medical condition contraindicating prophylaxis with cefazolin including allergy. Patients are randomized to receive a single preoperative intravenous dose of either 2 g of cefazolin or a placebo (NaCl). The primary analysis will be an intention-to-treat comparison of the proportion of patients with a SSI at 90 days after IR in both groups. DISCUSSION: If 2 g of prophylactic cefazolin proves to be both effective and cost-effective in preventing SSI, this would have implications for current guidelines. Combined with the high infection rate of IR which previous studies have shown, it would be sufficiently substantiated for guidelines to suggest protocolled use of prophylactic antibiotics in IR of foot, ankle, lower leg or patella. Trial registration Nederlands Trial Register (NTR): NL8284, registered on 9th of January 2020, https://www.trialregister.nl/trial/8284.

Clinical outcomes and costs associated with procalcitonin utilization in hospitalized patients with pneumonia, heart failure, viral respiratory infection, or chronic obstructive pulmonary disease.

Lower respiratory tract infections (LRTIs) due to bacterial pneumonia are common among hospitalized patients and are frequently treated with antibiotics. Viral illnesses and exacerbations of heart failure or COPD may present with symptoms mimicking a LRTI, resulting in unnecessary antibiotic utilization. Procalcitonin testing may be useful in these clinical scenarios. We attempted to assess the utility of procalcitonin testing versus not testing, and positive versus negative results among hospitalized patients with suspected LRTI. We performed a retrospective cohort study using multivariable analysis comparing clinical outcomes of patients with and without procalcitonin testing. Patients were 18 years or older, hospitalized for pneumonia, heart failure, COPD, or a viral respiratory illness between October 2014 and October 2015 (n = 2353). All patients received at least one dose of antibiotics. Major outcomes were duration of antibiotic therapy, length of hospital stay, C. difficile testing and infections, and normalized total direct costs. Procalcitonin testing occurred in 14.0% of patients and pneumonia (70.6%) was the most common diagnosis. After covariate adjustments, mean length of stay (5.61 vs. 6.67 days, p < 0.001) and duration of antibiotics (3.95 vs. 4.47 days, p < 0.001) were shorter among tested patients. Fewer 30-day readmissions (OR 0.62, 95% CI 0.40-0.95) were observed, and total direct healthcare costs were 34% lower (0.66, 95% CI 0.58-0.74) among tested patients. Negative procalcitonin results were associated with further reductions in some outcomes. In conclusion, procalcitonin testing among hospitalized patients with suspected LRTI is associated with reductions in antibiotic duration, length of stay, 30-day readmission, and healthcare costs.

A Minority of Patients on Mechanical Ventilation Consume Disproportionate Resources: A Retrospective Cohort Study.

BACKGROUND: The Pareto principle states that the majority of any effect comes from a minority of the causes. This property is widely used in quality improvement science. RESEARCH QUESTION: Among patients requiring mechanical ventilation (MV), are there subgroups according to MV duration that may serve as potential nodes for high-value interventions aimed at reducing costs without compromising quality? STUDY DESIGN AND METHODS: This multicenter retrospective cohort study included approximately 780 hospitals in the Premier Research Database (2014-2018). Patients receiving MV were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification, and International Classification of Diseases, Tenth Revision, codes. They were then divided into quintiles according to MV duration; their hospital costs, post-MV onset length of stay (LOS), ICU LOS, and cumulative post-MV onset hospital days per quintile were compared. RESULTS: A total of 691,961 patients were included in the analysis. Median [interquartile range] duration of MV in days by quintile was as follows: quintile 1 (Q1), 1 [1, 1]; Q2, 2 [2, 2]; Q3, 3 [3, 3]; Q4, 6 [6, 7]; and Q5, 13 [10, 19]. Median [interquartile range] post-MV onset LOS (Q1, 2 [0, 5]; Q5, 17 [12, 26]) and hospital costs (Q1, $15,671 [$9,180, $27,901]; Q5, $70,133 [$47,136, $108,032]) rose from Q1 through Q5. Patients in Q5 consumed 47.7% of all post-MV initiation hospital days among all patients requiring MV, and the mean per-patient hospital costs in Q5 exceeded the sum of costs incurred by Q1 to Q3. Adjusted marginal mean (95% CI) hospital costs rose exponentially from Q1 through Q5: Q2 vs Q1, $3,976 ($3,354, $4,598); Q3 vs Q2, $5,532 ($5,103, $5,961); Q4 vs Q3, $11,705 ($11,071, $12,339); and Q5 vs Q4, $26,416 ($25,215, $27,616). INTERPRETATION: Patients undergoing MV in the highest quintiles according to duration of MV consume a disproportionate amount of resources, as evidenced by MV duration, hospital LOS, and costs, making them a potential target for streamlining MV care.

Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial.

Rationale: Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear.Objectives: To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis.Methods: In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 µg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by Clostridioides difficile or multidrug-resistant organisms, or any death attributed to baseline C. difficile or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization.Measurements and Main Results: The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8-13.1%; 9/125) versus 15.3% (95% CI, 10.1-22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20-0.98; P = 0.045); 28-day mortality 15.2% (95% CI, 10-22.5%; 19/125) versus 28.2% (95% CI, 21.2-36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29-0.89; P = 0.02); and median length of antibiotic therapy 5 (range, 5-7) versus 10 (range, 7-15) days (P < 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm.Conclusions: In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization.Clinical trial registered with www.clinicaltrials.gov (NCT03333304).

Cost-effectiveness analysis of initial nonoperative management versus emergency laparoscopic appendectomy for acute complicated appendicitis.

BACKGROUND: The evidence regarding the safety and efficacy of nonoperative management is growing. However, the best treatment strategy for acute complicated appendicitis remains controversial. We aimed to evaluate the cost-effectiveness of treatment strategies for complicated appendicitis patients. This study sought to determine the most cost-effective strategy from the health care-payer's perspective. METHODS: The primary outcome was an incremental cost effectiveness ratio (ICER) using nonoperative management with or without interval laparoscopic appendectomy (ILA) as the intervention compared with operative management with emergency laparoscopic appendectomy (ELA) alone as the control. Model variables were abstracted from a literature review, and from data obtained from the hospital records of Tochigi Medical Center. Cost-effectiveness was evaluated using an ICER. We constructed a Markov model to compare treatment strategies for complicated appendicitis in otherwise-healthy adults, over a time horizon of a single year. Uncertainty surrounding model parameters was assessed via one-way- and probabilistic-sensitivity analyses. Threshold analysis was performed using the willingness-to-pay threshold set at the World Health Organization's criterion of $107,690. RESULTS: Three meta-analysis were included in our analysis. Operative management cost $6075 per patient. Nonoperative management with interval laparoscopic appendectomy (ILA) cost $984 more than operative management and produced only 0.005 more QALYs, resulting in an ICER of $182,587. Nonoperative management without ILA cost $235 more than operative management, and also yielded only 0.005 additional QALYs resulting in an ICER of $45,123 per QALY. Probabilistic sensitivity analysis with 1000 draws resulted in average ICER of $172,992 in nonoperative management with ILA and $462,843 in Nonoperative management without ILA. The threshold analysis demonstrated that regardless of willingness-to-pay, nonoperative management without ILA would not be most cost-effective strategy. CONCLUSIONS: Nonoperative management with ILA and Nonoperative management without ILA were not cost-effective strategies compared with operative management to treat complicated appendicitis. Based on our findings, operative management remains the standard of care and nonoperative management would be reconsidered as a treatment option in complicated appendicitis from economic perspective.

Cefuroxime (Aprokam®) in the Prophylaxis of Postoperative Endophthalmitis After Cataract Surgery Versus Absence of Antibiotic Prophylaxis: A Cost-Effectiveness Analysis in Poland.

OBJECTIVE: The analysis aims to assess the cost-effectiveness of cefuroxime (Aprokam®) in the prophylaxis of postoperative endophthalmitis (POE) after cataract surgery compared with the absence of antibiotic prophylaxis from the National Health Fund perspective in Poland. METHODS: We performed a cost-effectiveness and cost-utility analysis using the decision tree and Markov model, respectively, for patients after cataract surgery. The efficacy of Aprokam was 0.21 (95% confidence interval [CI], 0.08-0.55) and is based on the results of the European Society of Cataract and Refractive Surgery study. According to the epidemiological data from Poland, the risk of POE is 0.377%. The costs associated with the Aprokam administration and POE treatment costs were included. We determined the utilities of the health states in the model depending on visual loss due to POE. To determine the uncertainty of estimates parameters, a one-way deterministic and probabilistic sensitivity analysis were performed. RESULTS: Using Aprokam allows avoiding 0.003 POEs per patient. The benefit from the intervention is 0.0007 quality-adjusted life years per patient in the lifetime horizon. The total costs of prophylaxis are higher at about €1.70. The cost of avoiding one POE (incremental cost-effectiveness ratio) is about €569.85. The estimated incremental cost-effectiveness utility ratio is equal to €2427.72/quality-adjusted life-years, and it is significantly lower than the cost-effectiveness threshold in Poland in 2019 (about 7.5% of the threshold). In all scenarios of performed one-way sensitivity analyses, Aprokam is cost-effective. CONCLUSIONS: In Poland, the use of Aprokam is cost-effective, with the estimated incremental cost-utility ratio significantly lower than the cost-effectiveness threshold.

Levofloxacin prophylaxis in hospitalized children with leukemia: A cost-utility analysis.

BACKGROUND: Infections are common and are a major cause of morbidity and mortality during treatment of childhood leukemia. We evaluated the cost effectiveness of levofloxacin antibiotic prophylaxis, compared to no prophylaxis, in children receiving chemotherapy for acute myeloid leukemia (AML) or relapsed acute lymphoblastic leukemia (ALL). PROCEDURES: A cost-utility analysis was conducted from the perspective of the single-payer health care system using a lifetime horizon. A comprehensive literature review identified available evidence for effectiveness, safety, costs of antibiotic prophylaxis in children with leukemia, and health utilities associated with the relevant health states. The effects of levofloxacin prophylaxis on health outcomes, quality-adjusted life-years (QALY), and direct health costs were derived from a combined decision tree and state-transition model. One-way deterministic and probabilistic sensitivity analyses were performed to test the sensitivity of results to parameter uncertainty. RESULTS: The literature review revealed one randomized controlled trial on levofloxacin prophylaxis in childhood AML and relapsed ALL, by Alexander et al, that showed a significant reduction in rates of fever and neutropenia (71.2% vs 82.1%) and bacteremia (21.9% vs 43.4%) with levofloxacin compared to no prophylaxis. In our cost-utility analysis, levofloxacin prophylaxis was dominant over no prophylaxis, resulting in cost savings of $542.44 and increased survival of 0.13 QALY. In probabilistic sensitivity analysis, levofloxacin prophylaxis was dominant in 98.8% of iterations. CONCLUSIONS: The present analysis suggests that levofloxacin prophylaxis, compared to no prophylaxis, is cost saving in children receiving intensive chemotherapy for AML or relapsed ALL.

Cost-effectiveness of levofloxacin prophylaxis against bacterial infection in pediatric patients with acute myeloid leukemia.

BACKGROUND: Infections are the leading cause of therapy-related mortality in pediatric patients with acute myeloid leukemia (AML). Although effectiveness of levofloxacin antibacterial prophylaxis in oncology patients is recognized, its cost-effectiveness is unknown. This study evaluated epidemiologic data regarding levofloxacin use and the cost-effectiveness of this strategy as the cost per bacteremia episode, intensive care unit (ICU) admission, and death avoided in children with AML. PROCEDURE: A retrospective cohort study using the Pediatric Health Information System (PHIS) database compared demographic and clinical characteristics and receipt of levofloxacin prophylaxis in children with AML admitted for chemotherapy from January 1, 2014, through December 31, 2018. We then developed a decision analysis model in this population that compared costs associated with bacteremia, ICU admission, or death secondary to bacteremia to levofloxacin prophylaxis cost from a healthcare perspective. Time horizon is one chemotherapy cycle. Probabilistic and one-way sensitivity analyses evaluated model uncertainty. RESULTS: Prophylaxis cost $8491 per bacteremia episode prevented compared with an average added hospital cost of $119 478. Prophylaxis cost $81 609 per ICU admission avoided, compared with an average added hospital cost of $94 181. Prophylaxis cost $220 457 per death avoided. In sensitivity analysis, at a willingness-to-pay threshold of $100 000 per bacteremia episode avoided, prophylaxis remained cost-effective in 94.6% of simulations. Prophylaxis use was more common in recent years in patients with relapsed disease and with chemotherapy regimens considered more intensive. CONCLUSION: Prophylaxis is cost-effective in preventing bacterial infections in patients with AML. Findings support increased use in patients considered at high risk of bacterial infection secondary to myelosuppression.

The cost-effectiveness of empirical antibiotic treatments for high-risk febrile neutropenic patients: A decision analytic model.

PURPOSE: Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments. METHODS: A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness. RESULTS: The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options. DISCUSSION: Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

Management of infective complications of otitis media in resource-constrained settings.

PURPOSE OF REVIEW: Complications of otitis media are a cause of significant morbidity and mortality, compounded in resource-constrained settings in which human and physical resources to manage disease are suboptimal. Here, we examine the current best evidence to devise a protocol for management, in particular exploring the opportunity for conservative or nonspecialist management. RECENT FINDINGS: Reviews of the literature suggest that intratemporal and extracranial infections can be managed with antibiotics in the first instance, with aspiration or incision and drainage of abscess. Failure to respond necessitates mastoidectomy, which need not be extensive, and can be performed with hammer and gouge. Suspected or possible intracranial extension requires referral for computed tomography (CT) imaging. Intracranial infection can in some instances be managed with antibiotics, but large or persistent intracranial abscess, or the presence of cholesteatoma requires management in a centre for specialist surgery. SUMMARY: Many complications of otitis media could be managed by nonspecialists in appropriately equipped local or regional health facilities, and supported by appropriate training. However, regional centres with CT imaging and specialist surgery are required for assessment and treatment of cases that are suspected of having complex or advanced disease, or that fail to respond to initial treatment. Those involved in planning healthcare provision should look to develop infrastructure to support such management.

Impacto de un programa de optimización de uso de antimicrobianos en un hospital pediátrico de tercer nivel en Panamá / Impact of an antimicrobial stewardship program in a pediatric third level hospital in Panama

Resumen Introducción: Los programas de optimización de uso de antimicrobianos (PROA) se enfocan en el uso apropiado de antimicrobianos para ofrecer mejores resultados clínicos y menores riesgos de eventos adversos. Objetivos: Comparar consumo y costos de antimicrobianos antes y después de instauración de un programa de regulación de antimicrobianos y describir la proporción de resistencia de bacterias prioritarias. Métodos: Estudio cuasi-experimental, retrospectivo y prospectivo, descriptivo y analítico, que comparó el consumo y costo de antimicrobianos en un período pre- intervención (2007-2010) y un período post-intervención (2011-2017). Se realizó análisis descriptivo de resistencias bacterianas prioritarias. Resultados: El consumo de gentamicina, vancomicina, meropenem, cefotaxima, ceftazidima e imipenem disminuyó significativamente en el período post-intervención comparado con el período pre-intervención (p < 0,05), mientras que el consumo de amikacina, piperacilina/tazobactam, cefepime y levofloxacina en el período post-intervención mostró un aumento significativo. La reducción de costos no fue significativa para gentamicina, vancomicina, meropenem, cefotaxima, ceftazidima e imipenem. Para amikacina, cefepime, piperacilina/tazobactam y levofloxacina el aumento de costos no fue significativo. Los aislamientos de Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus y Enterococcus faecalis disminuyeron durante el período post-intervención. Conclusión: el PROA demostró disminución en consumo y costos de algunos antimicrobianos.

Abstract Background: Antimicrobial Stewardship Programs (ASP) focus in the appropriate use of antimicrobials to improve clinical results and minimize risk of adverse events. Aims: To compare consumption and costs of antimicrobials before and after the establishment of an antimicrobial stewardship program and to describe the resistance proportion of priority bacteria. Methods: Quasi-experimental, retrospective and prospective, descriptive and analytical study, to compare consumption and costs of antimicrobials in a pre- intervention period (2007-2010) and a post- intervention period (2011-2017). Additionally, a descriptive analysis of bacterial resistance from 2010 was performed. Results: Gentamicin, vancomycin, meropenem, cefotaxime, ceftazidime and imipenem consumption decreased significantly in the post-intervention period compared to the pre-intervention period (p < 0.05) while consumption of amikacin, piperacillin/tazobactam, cefepime and levofloxacin increased significantly in the post-intervention period. The reduction in costs was not significant for gentamicin, vancomycin, meropenem, cefotaxime, ceftazidime and imipenem, meanwhile, costs increased for amikacin, piperacillin/tazobactam, cefepime and levofloxacin, but this was not significant. The isolation of Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis decreased during the post-intervention period. Conclusion: The ASP showed a decrease in consumption and costs of some antimicrobials.