Future options for (economically) sustainable research in sepsis.

The relentless increase in healthcare costs and the global economic crisis require us to rethink the way research is done. The heterogeneity of patients is a major challenge in designing and coordinating high-quality studies about sepsis. Studies on new treatments and devices, such as polymyxin B hemoperfusion, must be optimized not only for potential benefits for a specific population (i.e. efficacy), but also for their eventual implementation in real-world situations (i.e. effectiveness) and for economic costs (i.e. efficiency). In this regard, theragnosis and newer statistical tools could help us obtain useful information from real-life observational data. In this review, we discuss the basic components required for sustainable research in polymyxin B hemoperfusion.

Cost-effectiveness analysis of polymyxin B versus colistin for treating patients with carbapenem-resistant gram-negative bacterial infections.

The prevalence of carbapenem-resistant gram-negative bacterial (CRGNB) infection is continuously increasing, and polymyxin B and colistin are considered last-resort drugs. This study compared the cost-effectiveness of polymyxin B with that of colistin for the treatment of intensive care unit patients with CRGNB infection from the Chinese healthcare perspective. A decision-analytic Markov model was constructed to assess the cost-effectiveness of polymyxin B compared with colistin over a period of 5 years using evidence from phase trials and other publicly available studies. The model was developed in Treeage Pro 2022 and comprises a decision tree depicting initial hospitalization and a Markov model with four states projecting long-term health and economic impacts following discharge. Uncertainty was tested with one-way sensitivity analyses and probabilistic sensitivity analyses. The quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratio (ICER) were estimated at willingness-to-pay (WTP) thresholds of $12,674 to $38,024 per QALY. According to the base analyses, the cost incurred by patients receiving colistin treatment was $12,244.77, leading to a gain of 1.35 QALYs. In contrast, patients treated with polymyxin B had a lower cost of $7,306.71 but yielded 1.07 QALYs. The ICRE of colistin was $18032.25/QALY. At a $12,674/QALY threshold, the results were sensitive to several variables, including the probability of cure with polymyxin B, the cost of drugs, the utility of discharge to home, the utility of discharge to long-term care, and the cost of nephrotoxicity with renal replacement therapy. After all model inputs varied across a wide range of reasonable values, only the probability of being cured with polymyxin B resulted in an ICER above the $38,024/QALY threshold. According to the probabilistic sensitivity analyses, colistin was the optimal strategy in 38.2% and 62.8% of the simulations, at $12,674/QALY and $38,024/QALY, respectively. Our study findings suggest that, when considering the Chinese healthcare perspective, colistin is likely to be more cost-effective than polymyxin B for patients with CRGNB infection, especially when the WTP threshold is set at one-time the per capita GDP. However, as the WTP threshold increases from one to three times the per capita GDP, the cost-effectiveness acceptability of colistin improves, increasing from 38.2 to 62.8%.

Colistin and polymyxin B for treatment of nosocomial infections in intensive care unit patients: pharmacoeconomic analysis.

Background The emergence and rapid spread of multidrug-resistant gram-negative bacteria related to nosocomial infections is a growing worldwide problem, and polymyxins have become important due to the lack of new antibiotics. Objectives To evaluate the outcomes and pharmacoeconomic impact of using colistin and polymyxin B to treat nosocomial infections. Setting Neurosurgical, cardiovascular, or transplantation intensive care unit (ICU) at the Clinical Hospital of the University of Campinas (São Paulo, Brazil). Method A retrospective cohort study was conduct in patients in the ICU. The renal function was determined daily during treatment by measuring the serum creatinine. A cost minimization analysis was performed to compare the relative costs of treatment with colistin and polymyxin B. Main outcomes measure The outcomes were 30-day mortality and frequency and onset of nephrotoxicity after beginning treatment. Results Fifty-one patients treated with colistin and 51 with polymyxin B were included. 30-day mortality was observed in 25.49% and 33.33% of patients treated with colistin and polymyxin B, respectively; Nephrotoxicity was observed in 43.14% and 54.90% of patients in colistin and polymyxin B groups, respectively; and onset time of nephrotoxicity was 9.86 ± 13.22 days for colistin and 10.68 ± 9.93 days for polymyxin B group. Colistin treatment had a lower cost per patient compared to the cost for polymyxin B treatment (USD $13,389.37 vs. USD $13,639.16, respectively). Conclusion We found no difference between 30-day mortality and nephrotoxicity between groups; however, colistin proved to be the best option from a pharmacoeconomic point of view.

Polymyxin B and colistin-the economic burden of nephrotoxicity against multidrug resistant bacteria.

BACKGROUND: Polymyxin B and colistin are nephrotoxic drugs used in the treatment of carbapenem-resistant Enterobacteriaceae. The aim of this study is to evaluate the burden of costs due to polymyxin associated AKI and propose a simulated break-even price for new therapies. METHODS: The pharmacoeconomic model is based on two large cross-sectional studies of polymyxin nephrotoxicity. Total direct costs in patients with and without renal failure were compared. The direct cost of each hemodialysis section (USD82.94) and daily hospital charges (USD934.85) were based on the values used in a major public hospital in the city where the clinical study was performed. The break-even price of new drugs was simulated considering eventual new drugs as effective as polymyxins, but less nephrotoxic in different percentages. Outcomes of patients after hospital discharge were not evaluated. RESULTS: Total direct cost of the group of patients who survived without AKI was significantly lower than total direct cost of the groups either with AKI or the group who died without AKI. There was a tendency of even higher costs in those who died with AKI and dialysis. Direct cost of hemodialysis was not as important as the longer hospitalization after sepsis. Considering daily cost of polymyxin is USD60, drugs with 50% less AKI could be considered cost-beneficial if the daily cost is lower than USD160. CONCLUSIONS: AKI in patients with carbapenem-resistant Enterobacteriaceae treated with polymyxin increases both length of stay in hospital and total costs.

Topical otic antibiotics: clinical cochlear ototoxicity and cost consideration.

OBJECTIVE: Determine the incidence of clinical cochlear ototoxicity in routine use of Cortisporin after ventilation tube placement. Cost differential between use of Cortisporin and fluoroquinolone agents was evaluated. METHODS: A retrospective review of 500 patients was performed. Cortisporin otic suspension was used for 5 days following ventilation tube insertion. RESULTS: Testing following surgery indicated a sensorineural hearing loss (SNHL) in 19 (2.1%) ears. The SNHL existed prior to the surgery and there was no deterioration in the hearing postoperatively. The total cost for our study group who used Cortisporin was $15,500. If Floxin had been prescribed the cost would have been $45,000. Had Ciprodex been prescribed, the cost would have been $49,500. CONCLUSION: Our study demonstrates no clinical cochlear ototoxicity in children who received Cortisporin following ventilation tube placement. The cost differential for prescribing fluoroquinolone drops is significant. EBM RATING: C-4.

Povidone iodine plus neosporin in superficial burns--a continuing study.

A total of 1053 patients with superficial burn injury were treated with povidone iodine plus neosporin (PVP + N) and the results after treatment were compared with those obtained after treating 1089 patients with silver sulphadiazine (SSD). Qualitative analysis showed Staphylococcus aureus and Pseudomonas spp. to be the most common infecting organisms. Quantitatively, fewer patients showed infection on the 7th and 18th day post-treatment in the PVP + N group (P < 0.01 and P < 0.001, respectively). Similarly, healing times were also better with PVP + N, with a maximum number of patients having healed within 15 days (P < 0.001). However, the mortality rates were not much different between the two groups.

[Ophthalmic preparations Polyspectran (combination of neomycin, polymyxin B and bacitracin/gramicidin) and Terramycin (oxytetracycline with polymyxin B) mistakenly no longer reimbursed]. / Oogheelkundige preparaten Polyspectran (combinatie van neomycine, polymyxine B en bacitracine/gramicidine) en Terramycine (oxytetracycline met polymyxine B) ten onrechte niet meer vergoed.

The Netherlands' Ministry of Health and the health insurance companies have drawn up a list of preparations which will no longer be reimbursed. The ocular antibiotic preparations Polyspectran and Terramycin are on the list. However, there are no satisfactory alternative with respect to the broadness of the antibiotic spectrum required. In addition, some alternatives have serious side effects or may induce bacterial resistance.