Comparative evaluation of agar dilution and broth microdilution by commercial and in-house plates for Bacteroides fragilis group: An economical and expeditious approach for resource-limited settings.

OBJECTIVE: To compare the performance of agar dilution and broth microdilution by commercial and in-house prepared plates for the Bacteroides fragilis group. The cost analysis was performed to demonstrate that in-house prepared BMD plates were a suitable alternative to agar dilution given the high cost and low feasibility of incorporating commercial BMD plates in routine, particularly in the tertiary care institutes of many low- and middle-income countries. METHODS: Thirty B. fragilis group isolates were tested against six antibiotics, frequently used as empirical therapy for anaerobic infections including metronidazole, clindamycin, imipenem, piperacillin-tazobactam, cefoxitin, and chloramphenicol. The running consumable expenditure for all methodologies was calculated. RESULTS: The results demonstrated essential and categorical agreement of >90% for all antibiotics except cefoxitin, which showed <90% categorical agreement. No major or very major errors were observed. We observed a high agreement and strong concordance for MIC values between both methods and inter-rate reliability of >0.9 by Cohen's kappa analysis, indicating almost perfect agreement between both methods using either of the plates. In contrast to agar dilution, a 20.5 fold cost reduction was seen in BMD using in-house plates and a 5.8 fold reduction using commercial plates to test a single isolate. However, when testing 30 isolates concurrently the cost significantly increased for commercial BMD plates by 8.4 folds, and only 1.03 fold cost reduction was seen with in-house BMD plates. CONCLUSION: BMD gives comparable results to agar dilution and can be considered a method of choice to test a small number of samples. The technique is an economical option when plates are standardized in-house and could be employed for susceptibility testing of the B. fragilis group.

Helicobacter pylori eradication regimens in an antibiotic high-resistance European area: A cost-effectiveness analysis.

INTRODUCTION: Helicobacter pylori infection (H pylori-I) affects more than half of the global population and consists an important burden to public health and healthcare expenditures, by contributing to many diseases' pathogenesis. AIM: This study aimed to evaluate the current nonbismuth quadruple eradication regimens in a high antibiotic resistance area, such as Greece, concerning their cost-effectiveness, especially during financial crisis period. MATERIALS AND METHODS: Eight hundred and nine patients who received eradication treatment against H pylori-I were included to evaluate five different regimens, using amoxicillin, clarithromycin, and metronidazole as antibiotics and one proton-pump inhibitor, based on their current eradication rates. Regimes compared 10-day concomitant use of (a) pantoprazole or (b) esomeprazole; 10-day sequential use of (c) pantoprazole or (d) esomeprazole; and 14-day hybrid using esomeprazole. Cost-effectiveness analysis ratio (CEAR) and incremental cost-effectiveness ratios were calculated taking into account all direct costs and cases who needed second-line treatment. Additionally, sensitivity analysis was performed to predict all potential combinations. RESULTS: Ten-day concomitant regimen with esomeprazole was characterized by the lowest CEAR (179.17€) followed by the same regimen using pantoprazole (183.27€). Hybrid regimen, although equivalent in eradication rates, was found to have higher CEAR (187.42€), whereas sequential regimens were not cost-effective (CEAR: 204.12€ and 216.02€ respectively). DISCUSSION: This is the first study evaluating the cost-effectiveness of H pylori-I treatment regimens in a high clarithromycin-resistance (≈26.5%) European area, suggesting the 10-day concomitant regimen with generics using esomeprazole 40 mg as the most appropriate one. National and regional guidelines should include cost-effectiveness in their statements, and further studies are required to clarify the necessity of a wide "test and treat" policy for H pylori-I.

The Trend for Antibiotic Use for Clostridioides (Clostridium) difficile Infection in Japan.

In Japan, there is no national surveillance study of Clostridioides (Clostridium) difficile infection (CDI), and details about the epidemiology and treatment status of CDI are unknown. Additionally, clinical practice guidelines (CPGs) for CDI are published by four different institutions. All CPGs recommend that the antimicrobials, vancomycin (VCM) and metronidazole (MNZ), should be selected according to disease severity. However, the trends for VCM and MNZ use in Japan remain unclear. Therefore, this study was aimed at clarifying the secular trends for VCM and MNZ use based on sales data from 2006 to 2015 and discussing its impact on CDI status and drug costs. This is the first study to clarify the antibiotic use trends for CDI treatment. We found that the total use increased over time (r = 0.0013, Pfor trend < 0.0001). While VCM use significantly decreased (r = -0.0003, Pfor trend = 0.0002), MNZ use increased (r = 0.0017, Pfor trend < 0.0001). These results show that although treatment for CDI was in line with CPGs, CDI incidence might be on an increasing trend. Additionally, despite the increased total use, the total drug costs decreased by 55% ($ 25 million) from 2006 to 2015. It was also surmised that CDI treatment in compliance with CPGs would lead to a reduction in drug costs. Hence, to understand the epidemiology of CDI, it is important to continuously investigate the use of drugs used for CDI therapy.

Rosacea Treatment Satisfaction: Matching Adjusted Indirect Treatment Comparison Analysis of Metronidazole Gel or Cream vs Azelaic Acid Foam.

OBJECTIVE: To assess differences in patient-reported treatment side effects and concerns associated with azelaic acid 15% foam (AAF) vs metronidazole cream (MC) and metronidazole gel (MG). METHODS: This study used matching-adjusted indirect comparison (MAIC) to compare patient-reported outcomes from survey data evaluating rosacea treatments. Outcomes of interest included percentages of patients reporting concerns and side effects and measures of importance of the concerns and tolerability of the side effects. Patients in each analysis (MG vs AAF and MC vs AAF) were matched using stabilized inverse propensity scores. RESULTS: When compared to AAF, MG-treated patients more frequently reported concerns with treatment efficacy (54% vs 4%), application (7% vs 3%), and treatment side effects. MC-treated patients more frequently reported concerns with treatment efficacy (61% vs 5%) and dryness (8% vs 5%). AAF-treated patients more frequently reported concerns with cost of treatment compared with MG (7% vs 1%) and MC (9% vs 4%). Among patients reporting concerns, level of importance associated with these concerns was similar for AAF-treated patients compared with MG- and MC-treated patients. When compared to AAF-treated patients, MG-treated patients more frequently reported side effects of dryness (26% vs 15%) and uneven skin tone (3% vs 0%), and MC-treated patients more frequently reported side effects of burning (7% vs 3%), itching (7% vs 5%), and redness (7% vs 5%). MG- and MC-treated patients indicated greater intolerance for reported side effects than AAF-treated patients. CONCLUSIONS: MG- and MC-treated patients more frequently reported treatment concerns and side effects than AAF-treated patients, and tolerability of those side effects was higher for patients treated with AAF. While treatment cost is a more frequent concern in patients treated with AAF, these patients less frequently reported concerns with treatment efficacy and reported similar or greater tolerance to side effects than patients treated with either MC or MG. J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.3679.

Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial.

BACKGROUND: An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial. METHODS: The APPAC multicentre, non-inferiority RCT was conducted on patients with CT-confirmed uncomplicated acute appendicitis. Patients were assigned randomly to appendicectomy or antibiotic treatment. All costs were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis during the 1-year follow-up. The cost estimates were based on cost levels for the year 2012. RESULTS: Some 273 patients were assigned to the appendicectomy group and 257 to antibiotic treatment. Most patients randomized to antibiotic treatment did not require appendicectomy during the 1-year follow-up. In the operative group, overall societal costs (€5989·2, 95 per cent c.i. 5787·3 to 6191·1) were 1·6 times higher (€2244·8, 1940·5 to 2549·1) than those in the antibiotic group (€3744·4, 3514·6 to 3974·2). In both groups, productivity losses represented a slightly higher proportion of overall societal costs than all treatment costs together, with diagnostics and medicines having a minor role. Those in the operative group were prescribed significantly more sick leave than those in the antibiotic group (mean(s.d.) 17·0(8·3) (95 per cent c.i. 16·0 to 18·0) versus 9·2(6·9) (8·3 to 10·0) days respectively; P < 0·001). When the age and sex of the patient as well as the hospital were controlled for simultaneously, the operative treatment generated significantly more costs in all models. CONCLUSION: Patients receiving antibiotic therapy for uncomplicated appendicitis incurred lower costs than those who had surgery.

Cost-effectiveness analysis of annual Trichomonas vaginalis screening and treatment in HIV-positive women to prevent HIV transmission.

BACKGROUND: Because of a high incidence of Trichomonas infection among HIV-positive women, annual screening and treatment are recommended. Trichomonas infection is associated with a 2-fold risk of HIV transmission. The objective of this study was to determine if annual screening is cost-effective for the prevention of new HIV cases in susceptible male partners secondary to Trichomonas infection in HIV-positive women. METHODS: A decision tree analysis was constructed to model the costs of Trichomonas screening, treatment, and follow-up. 200 women cycled through the model for a period of 12 months. One hundred women were unscreened and 100 were screened and treated per recommendations. RESULTS: Annual Trichomonas screening and treatment saves US $553 (US $475- US $645) per woman in the prevention of HIV transmission to male partners. The cost-effectiveness of this strategy was maintained across all assumptions in a sensitivity analysis. CONCLUSIONS: Trichomonas screening and treatment for the purpose of decreasing new HIV infections is not only cost-effective but also cost saving in HIV-positive women. If Centers for Disease Control and Prevention treatment guidelines were followed in all HIV-positive women living in the United States, the lifetime cost of new HIV infections prevented would approximate US $159,264,000 and could potentially prevent new HIV cases secondary to female-to-male transmissions.

A quantity survey of intravenous administration of metronidazole in its different forms in a tertiary teaching hospital.

The aim of this paper is to examine the prescribing patterns and cost of various formulations of metronidazole in a hospital setting over a 3-month period. Oral metronidazole has high bioavailability (98.9%) with peak plasma concentrations averaged at 2.3 h after dosing. Despite the high bioavailability of oral metronidazole, many patients continue to receive metronidazole intravenously when they are suitable for oral preparation. An audit of 120 consecutive patients prescribed metronidazole was conducted at the Liverpool Hospital, NSW, from March to July 2005. There were 65 men and 55 women (age 18-93). Of the 120 patients, 16 were on oral, 1 on rectal and 103 were on intravenous metronidazole. Treatment was initiated based on clinical diagnoses. Potential pathogens were subsequently identified on only 21 occasions. The use of metronidazole as an oral preparation was contraindicated in 27 patients (22.5%) who were nil-by-mouth. Of these, rectally administered metronidazole was contraindicated in only eight patients. The average course of intravenous metronidazole was 8.0 +/- 9.7 days (mean +/- SD). The total number of intravenous metronidazole treatment days was 824. Oral metronidazole would have been possible in 618 out of the 824 days. The estimated cost to administer each dose of oral, suppository and intravenous forms of metronidazole is $A0.11, $A1.34 and $A6.09 respectively. Thus, substantial savings could be achieved if oral metronidazole were to be administered whenever possible. The early use of oral or rectal metronidazole should be encouraged when there are no clinical contraindications.

Metronidazole versus lactic acid for treating bacterial vaginosis (VITA): protocol for a randomised controlled trial to assess the clinical and cost effectiveness of topical lactic acid gel for treating second and subsequent episodes of bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) affects 30-50% of women at some time in their lives and is an embarrassing and distressing condition which can be associated with potentially serious comorbidities. Current antibiotic treatments such as metronidazole are effective but can result in side effects, and recurrence is common. This trial aims to investigate whether lactic acid gel is clinically effective and cost effective in the treatment of recurrent BV compared with metronidazole. METHODS: VITA is an open-label, multicentre, parallel group randomised controlled trial for women with a clinical diagnosis of BV and at least one previous BV episode in the past 2 years. Participants will be randomised 1:1 to intravaginal lactic acid gel 5 ml once daily for 7 days or oral metronidazole tablets 400 mg twice daily for 7 days. All participants will be followed up for 6 months to assess health status and healthcare costs. A subgroup will be interviewed to further explore adherence, tolerability and acceptability of treatment. The estimated sample size is 1900 participants to detect a 6% absolute increase in response rate to 86% in those receiving lactic acid gel. The primary outcome is participant-reported resolution of BV at Week 2. DISCUSSION: Results from this trial will help inform UK treatment guidelines for BV and may provide an alternative effective treatment for recurrent episodes of this condition which avoids repeated exposure to antibiotics. TRIAL REGISTRATION: ISRCTN, ISRCTN14161293. Registered on 8 September 2017.

Cost analysis of antibiotic therapy versus appendectomy for treatment of uncomplicated acute appendicitis: 5-year results of the APPAC randomized clinical trial.

BACKGROUND: The efficacy and safety of antibiotic treatment for uncomplicated acute appendicitis has been established at long-term follow-up with the majority of recurrences shown to occur within the first year. Overall costs of antibiotics are significantly lower compared with appendectomy at short-term follow-up, but long-term durability of these cost savings is unclear. The study objective was to compare the long-term overall costs of antibiotic therapy versus appendectomy in the treatment of uncomplicated acute appendicitis in the APPAC (APPendicitis ACuta) trial at 5 years. METHODS AND FINDINGS: This multicentre, non-inferiority randomized clinical trial randomly assigned 530 adult patients with CT-confirmed uncomplicated acute appendicitis to appendectomy or antibiotic treatment at six Finnish hospitals. All major costs during the 5-year follow-up were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis. Between November 2009 and June 2012, 273 patients were randomized to appendectomy and 257 to antibiotics. The overall costs of appendectomy were 1.4 times higher (p<0.001) (€5716; 95% CI: €5510 to €5925) compared with antibiotic therapy (€4171; 95% CI: €3879 to €4463) resulting in cost savings of €1545 per patient (95% CI: €1193 to €1899; p<0.001) in the antibiotic group. At 5 years, the majority (61%, n = 156) of antibiotic group patients did not undergo appendectomy. CONCLUSIONS: At 5-year follow-up antibiotic treatment resulted in significantly lower overall costs compared with appendectomy. As the majority of appendicitis recurrences occur within the first year after the initial antibiotic treatment, these results suggest that treating uncomplicated acute appendicitis with antibiotics instead of appendectomy results in lower overall costs even at longer-term follow-up.

Vancomycin for the treatment of Clostridium difficile Infection: for whom is this expensive bullet really magic?

The epidemiology, clinical severity, and case-fatality ratio of Clostridium difficile infection (CDI) changed dramatically with the emergence of a toxin hyperproducing strain (BI/NAP1/027) in North America and Europe in 2000. For the treatment of CDI, metronidazole and vancomycin remain the 2 most commonly used drugs. The 3 randomized controlled trials published thus far, as well as the upcoming tolevamer trial, use intermediate outcomes, rather than the outcomes that now preoccupy clinicians: the frequency of complications or recurrence. The major advantage of metronidazole is its low price. The major advantage of orally administered vancomycin is its more favorable pharmacokinetics. Facilitating vancomycin-resistant enterococci colonization and/or infection is a potential drawback of both drugs. Pending the development of a prospectively validated scoring system, members of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America expert committee will define severe CDI as present in any patient with a leukocyte count > or =15,000 cells/mm(3) or a creatinine level increased by > or =50% from baseline. For patients with mild-to-moderate CDI (defined by a leukocyte count <15000 cells/mm(3) and a creatinine level <1.5 times the baseline value), there is no evidence that treatment with vancomycin is superior to treatment with metronidazole (even for intermediate outcomes), and metronidazole therapy should be preferred. For patients with severe CDI who are not infected with BI/NAP1/027, there is reasonable evidence that the better pharmacokinetics of vancomycin translate into a lower probability of complications. For those patients who are infected with BI/NAP1/027, the superiority of vancomycin therapy remains to be proven. In practice, because it is not yet possible to rapidly type the strains, all patients with severe CDI should be treated with vancomycin. Future trials should use complicated CDI and recurrences as their primary outcomes.

Do patients consider postoperative maintenance therapy for Crohn's disease worthwhile?

BACKGROUND: Treatment decision making for postoperative Crohn's disease is complex because of the increasing number of maintenance therapies available with competing risk-benefit profiles. The main objective of this study was to determine the distribution of patients' preferences for selected postoperative maintenance therapies. METHODS: The study was a cross-sectional survey in which patients with Crohn's disease completed a standardized interview. Each participant completed 5 tasks that compared: (1) no medication and 5-ASA, (2) fish oil and 5-ASA, (3) metronidazole and 5-ASA, (4) budesonide and 5-ASA, and (5) azathioprine and 5-ASA. For each task, the minimum change in treatment effect size between the 2 treatments that the participant considered worthwhile was determined. RESULTS: The distribution of the participants' preference scores varied widely for each task. When fish oil, metronidazole, budesonide, and azathioprine were considered equally effective to 5-ASA, 92.9%, 28.8%, 38.4%, and 19% of the participants, respectively, preferred these medications relative to 5-ASA. These percentages increased to 98.4%, 54.8%, 61.9%, and 50.8%, respectively, when fish oil, metronidazole, budesonide, and azathioprine were considered to offer a 5% absolute risk reduction relative to 5-ASA. Regression analysis did not identify any clinical or demographic variables predictive of the participants' treatment preferences. CONCLUSIONS: The participants' preferences for postoperative maintenance therapies were widely distributed, and no clinical or demographic factors predicted these preferences. This emphasizes the need for effective communication between physician and patient in order to select the treatment options most consistent with a patient's informed preferences.

Cost-effectiveness of quantitative fecal lactoferrin assay for diagnosis of symptomatic patients with ileal pouch-anal anastomosis.

BACKGROUND AND AIMS: To assess cost-effectiveness of fecal lactoferrin (FL) as the initial diagnostic approach to symptomatic patients with ileal pouch-anal anastomosis (IPAA). METHODS: Four competing strategies [empiric metronidazole therapy (txMTZ), initial pouch endoscopy with biopsy (testBiop), initial FL assay followed by metronidazole therapy (testFL+MTZ), and initial FL assay followed by pouch endoscopy and biopsy (testFL+Biop)] were modeled in a decision tree. RESULTS: In the base-case, the average cost per patient was $241 for testFL+MTZ, $251 for txMTZ, $405 for testFL+Biop, and $431 for testBiop. The testBiop strategy had greater effectiveness compared with txMTZ but at an incremental cost of $158 per day. The txMTZ strategy was slightly more costly and minimally more effective than testFL+MTZ with an incremental cost effectiveness of just over $12 per day. However, the testFL+MTZ strategy was associated with a 31% absolute reduction in antibiotic exposure compared with the txMTZ strategy. CONCLUSIONS: Compared with empiric metronidazole therapy, FL before treatment with metronidazole is less costly with less exposure to antibiotics and less need for endoscopy, with only marginal decrease in effectiveness.

Cost-effectiveness study comparing cefoperazone-sulbactam to a three-drug combination for treating intraabdominal infections in an Indian health-care setting.

OBJECTIVE: This article presents the methodology and results of the pharmacoeconomic analysis of the Magnex Against Standard COmbination Therapy study comparing cefoperazone-sulbactam (Magnex) versus ceftazidime+ amikacin+metronidazole, in the treatment of intra-abdominal infections. METHODS: This prospective, open label, phase IV study was conducted at 17 study sites in India and randomized subjects to receive either cefoperazone-sulbactam or the combination. Pharmacoeconomic analysis was included as a secondary objective and conducted in the clinical efficacy-evaluable (CEE) and the successfully treated patients. All comparisons between treatment groups were conducted using analysis of variance (ANOVA) or Wilcoxon Two-Sample tests. All costs were reported as Indian Rupee (INR) and actual unit costs collected in 2006 were used for the analyses [1 USD approximately 40 INR; 1 Euro approximately 56 INR]. RESULTS: In the CEE and the successfully treated subset of patients, the average cost of treatment was numerically lower in the cefoperazone-sulbactam arm (not statistically significant). The analyses found that the cost-effectiveness ratio (CER) for cefoperazone-sulbactam was INR 17,640.53 and that for the comparator group was INR 22,075.16. Additionally, the incremental CER results showed that the cost of treatment was INR 21,505.59 lower per additional successfully treated patient in the cefoperazone-sulbactam group. CONCLUSIONS: The present study was the first of its kind to be conducted in the "price sensitive" Indian health-care setting. Though study was not powered for the difference in average cost of treatments, there was a trend favoring cefoperazone sulbactam. The findings from this study should encourage further conduct of similar analyses and increase the knowledge regarding pharmacoeconomics in India.

Pharmacoeconomics of ciprofloxacin plus metronidazole vs. piperacillin-tazobactam for complicated intra-abdominal infections.

BACKGROUND: A series of 459 hospitalized adults with complicated intra-abdominal infections participated in a randomized, double-blind, multicenter clinical trial. The present study was conducted to add a pharmacoeconomic analysis to the results. METHODS: A cost-effectiveness analysis from the perspective of the hospital provider was carried out. Decision analysis was used to illustrate outcomes and to provide a basis on which to conduct a sensitivity analysis. Cost-effectiveness ratios, representing the cost per expected successfully treated patient, were calculated to determine the most cost-effective alternative. RESULTS: Among 244 economically evaluable patients, enrolled from 34 centers in the U.S. and Canada, 131 patients received ciprofloxacin-metronidazole (75% clinical success rate), and 113 received piperacillin-tazobactam (65% clinical success rate; p = 0.06). Switch to oral antibiotics was possible for 81 patients who received ciprofloxacin-metronidazole (85% clinical success rate) and 67 piperacillin-tazobactam patients (70% clinical success rate; p = 0.027). The mean hospital cost was US$10,662 +/- 7,793 for patients in the ciprofloxacin-metronidazole group and $10,009 +/- 7,023 for patients in the piperacillin-tazobactam group (p = 0.492). Significantly lower costs were documented for patients who could be switched to oral antibiotics than for those continued on intravenous antibiotic orders ($8,684 +/- 4,120 vs. $12,945 +/- 10,204, respectively; p < 0.001). Patients with appendicitis had lower mean hospital costs than those with other infections ($7,169 +/- 3,705 vs. $12,097 +/- 8,342, respectively; p < 0.001). The cost-effectiveness ratios were $14,216:1 for patients in the ciprofloxacin-metronidazole group and $15,398:1 for patients in the piperacillin-tazobactam group. CONCLUSIONS: The mean hospital costs associated with ciprofloxacin-metronidazole were similar to those of piperacillin-tazobactam for the treatment of adults with complicated intra-abdominal infections. Lower costs were documented for patients able to be switched to oral antibiotics and for patients with appendicitis.

Prescription refills and healthcare costs associated with topical metronidazole in Medicaid enrolled patients with rosacea.

BACKGROUND: Refill adherence to medications and healthcare costs are important factors to consider while making informed decisions regarding the treatment of rosacea patients. OBJECTIVE: The objective of this study was to examine predictors of number of refills related to topical metronidazole and total healthcare costs in rosacea patients. METHODS: This study utilized a longitudinal cohort design and followed rosacea patients enrolled in North Carolina Medicaid and who were prescribed at least one study medication (topical metronidazole, adapalene, azelaic acid, permethrin, and sulfacetamide). Patients' demographic characteristics, number of metronidazole refills, and different components of healthcare costs were examined. RESULTS: Out of the total 2587 rosacea patients, the majority (approximately 69%, n=1771) had one or more prescriptions for topical metronidazole. Most of the patients in this study were white (73%). After controlling for other variables, increasing age was associated with a higher number of metronidazole refills and healthcare costs (both p<0.001). Compared with white patients, African American patients had a significantly lower number of metronidazole refills (p<0.001). Compared with white patients, African American patients and 'other' races were associated with an 8.6% and 10.3% decrease in total healthcare costs respectively (both p<0.001). An increase in the number of metronidazole refills was not associated with an increase in healthcare costs. CONCLUSION: Patients' race is significantly associated with the number of topical metronidazole refills. Patients' healthcare costs increased with increasing age and charges paid for prescriptions. Topical metronidazole seems to be an economically feasible treatment option for Medicaid-enrolled patients with rosacea.

Metronidazole stewardship initiative at Christchurch hospitals-achievable with immediate benefits.

AIMS: To evaluate an antimicrobial stewardship (AMS) initiative to change hospital prescribing practice for metronidazole. METHODS: In October 2015, the Canterbury District Health Board (CDHB) AMS committee changed advice for metronidazole to promote two times daily dosing for most indications, prioritisation of the oral route and avoidance of double anaerobic cover. Adoption of the initiative was facilitated via change in prescribing guidelines, education and ongoing pharmacy support. Usage and expenditure on metronidazole for adult inpatients were compared for the five years pre- and two years post-change. Other district health boards (DHBs) were surveyed to determine their dosing recommendation for metronidazole IV. RESULTS: Mean annual metronidazole IV use, as defined daily doses per 1,000 occupied bed days, decreased by 43% post-initiative. Use of non-IV (oral or rectal) formulations increased by 104%. Total savings associated with the initiative were approximately $33,400 in drug costs plus $78,200 per annum in IV giving sets and post-dose flushes. Twelve of 20 (60%) DHBs (including CDHB) endorse twice daily IV dosing. CONCLUSIONS: In addition to financial savings, reduction in IV doses has potential benefits, including avoidance of IV catheter-associated complications such as bloodstream infections. Approaches to metronidazole dosing vary across DHBs and could benefit from national coordination.

A Systematic Literature Review of Economic Evaluations of Antibiotic Treatments for Clostridium difficile Infection.

BACKGROUND AND OBJECTIVE: Clostridium difficile infection (CDI) is associated with high management costs, particularly in recurrent cases. Fidaxomicin treatment results in lower recurrence rates than vancomycin and metronidazole, but has higher acquisition costs in Europe and the USA. This systematic literature review summarises economic evaluations (EEs) of fidaxomicin, vancomycin and metronidazole for treatment of CDI. METHODS: Electronic databases (MEDLINE®, Embase, Cochrane Library) and conference proceedings (ISPOR, ECCMID, ICAAC and IDWeek) were searched for publications reporting EEs of fidaxomicin, vancomycin and/or metronidazole in the treatment of CDI. Reference bibliographies of identified manuscripts were also reviewed. Cost-effectiveness was evaluated according to the overall population of patients with CDI, as well as in subgroups with severe CDI or recurrent CDI, or those at higher risk of recurrence or mortality. RESULTS: Overall, 27 relevant EEs, conducted from the perspective of 12 different countries, were identified. Fidaxomicin was cost-effective versus vancomycin and/or metronidazole in 14 of 24 EEs (58.3%), vancomycin was cost-effective versus fidaxomicin and/or metronidazole in five of 27 EEs (18.5%) and metronidazole was cost-effective versus fidaxomicin and/or vancomycin in two of 13 EEs (15.4%). Fidaxomicin was cost-effective versus vancomycin in most of the EEs evaluating specific patient subgroups. Key cost-effectiveness drivers were cure rate, recurrence rate, time horizon, drug costs and length and cost of hospitalisation. CONCLUSIONS: In most EEs, fidaxomicin was demonstrated to be cost-effective versus metronidazole and vancomycin in patients with CDI. These results have relevance to clinical practice, given the high budgetary impact of managing CDI and increasing restrictions on healthcare budgets. OTHER: This analysis was initiated and funded by Astellas Pharma Inc.

Cost-effectiveness of ceftolozane/tazobactam plus metronidazole compared with piperacillin/tazobactam as empiric therapy for the treatment of complicated intra-abdominal infections based on the in-vitro surveillance of bacterial isolates in the UK.

AIMS: An increase in the prevalence of antimicrobial resistance among gram-negative pathogens has been noted recently. A challenge in empiric treatment of complicated intra-abdominal infection (cIAI) is identifying initial appropriate antibiotic therapy, which is associated with reduced length of stay and mortality compared with inappropriate therapy. The objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam + metronidazole compared with piperacillin/tazobactam (commonly used in this indication) in the treatment of patients with cIAI in UK hospitals. METHODS: A decision-analytic Monte Carlo simulation model was used to compare costs (antibiotic and hospitalization costs) and quality-adjusted life years (QALYs) of patients infected with gram-negative cIAI and treated empirically with either ceftolozane/tazobactam + metronidazole or piperacillin/tazobactam. Bacterial isolates were randomly drawn from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database, a surveillance database of non-duplicate bacterial isolates collected from patients in the UK infected with gram-negative pathogens. Susceptibility to initial empiric therapy was based on the measured susceptibilities reported in the PACTS database. RESULTS: Ceftolozane/tazobactam + metronidazole was cost-effective when compared with piperacillin/tazobactam, with an incremental cost-effectiveness ratio (ICER) of £4,350/QALY and 0.36 hospitalization days/patient saved. Costs in the ceftolozane/tazobactam + metronidazole arm were £2,576/patient, compared with £2,168/patient in the piperacillin/tazobactam arm. The ceftolozane/tazobactam + metronidazole arm experienced a greater number of QALYs than the piperacillin/tazobactam arm (14.31/patient vs 14.21/patient, respectively). Ceftolozane/tazobactam + metronidazole remained cost-effective in one-way sensitivity and probabilistic sensitivity analyses. CONCLUSIONS: Economic models can help to identify the appropriate choice of empiric therapy for the treatment of cIAI. Results indicated that empiric use of ceftolozane/tazobactam + metronidazole is cost-effective vs piperacillin/tazobactam in UK patients with cIAI at risk of resistant infection. This will be valuable to commissioners and clinicians to aid decision-making on the targeting of resources for appropriate antibiotic therapy under the premise of antimicrobial stewardship.

Once-Daily Ceftriaxone Plus Metronidazole Versus Ertapenem and/or Cefoxitin for Pediatric Appendicitis.

BACKGROUND: Appendicitis is a common surgical emergency in pediatric patients, and broad-spectrum antibiotic therapy is warranted in their care. A simplified once-daily regimen of ceftriaxone and metronidazole (CTX plus MTZ) is cost effective in perforated patients. The goal of this evaluation is to compare a historic regimen of cefoxitin (CFX) in nonperforated cases and ertapenem (ERT) in perforated and abscessed cases with CTX plus MTZ for all cases in terms of efficacy and cost. METHODS: A retrospective review compared outcomes of nonperforated, perforated, and abscessed cases who received the historic regimen or CTX plus MTZ. Length of stay, time to afebrile, time to full feeds, postoperative abscess, and wound infection rates, inpatient readmissions, and antibiotic costs were evaluated. RESULTS: There were a total of 841 cases reviewed (494 nonperforated, 247 perforated, and 100 abscessed). Overall, the CTX plus MTZ group had a shorter time to afebrile (P < .001). Treatment groups did not differ in length of stay. Postoperative abscess rates were similar between groups (4.1% vs 3.3%, not significant). Other postoperative complications were similar between groups. Total antibiotic cost savings were over $110 000 during the study period (from November 2010 to June 2013). CONCLUSIONS: Both CFX and/or ERT and CTX plus MTZ result in low abscess and complication rates, suggesting both are effective strategies. Treatment with CTX plus MTZ results in a shorter time to afebrile, while also providing significant antibiotic cost savings. Ceftriaxone plus MTZ is a streamlined, cost-effective regimen in the treatment of nonperforated, perforated, and abscessed appendicitis.