Two drugs facing key patent expirations and potential generic entry from July to August 2020.

A challenge in anticipating generic entry is elucidating which patents and regulatory protections constrain generic entry.

Addressing Neisseria gonorrhoeae Treatment Resistance With the DNA Gyrase A Assay: An Economic Study, United States.

Targeted antibiotics could delay emergence of resistant Neisseria gonorrhoeae. The DNA gyrase subunit A assay predicts susceptibility to ciprofloxacin. A model found that adding a $50 gyrase subunit A test for asymptomatic patients screened for N. gonorrhoeae resulted in cost neutrality. When ciprofloxacin susceptibility was high, a $114 test resulted in savings.

Oral versus intravenous antibiotics for patients with Klebsiella pneumoniae liver abscess: study protocol for a randomized controlled trial.

BACKGROUND: Klebsiella pneumoniae liver abscess is the most common etiology of liver abscess in Singapore and much of Asia, and its incidence is increasing. Current management includes prolonged intravenous antibiotic therapy, but there is limited evidence to guide oral conversion. The implicated K1/K2 capsule strain of Klebsiella pneumoniae is almost universally susceptible to ciprofloxacin, an antibiotic with high oral bioavailability. Our primary aim is to compare the efficacy of early (< one week) step-down to oral antibiotics, to continuing four weeks of intravenous antibiotics, in patients with Klebsiella liver abscess. METHODS/DESIGN: The study is designed as a multi-center randomized open-label active comparator-controlled non-inferiority trial, with a non-inferiority margin of 12%. Eligible participants will be inpatients over the age of 21 with a CT or ultrasound scan suggestive of a liver abscess, and Klebsiella pneumoniae isolated from abscess fluid or blood. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. Participants randomized to active control will receive IV ceftriaxone 2 grams daily to complete a total of four weeks of IV antibiotics. Participants randomized to intervention will be immediately converted to oral ciprofloxacin 750 mg twice daily. At Week four, all participants will undergo abdominal imaging and be assessed for clinical response (CRP < 20 mg/l, absence of fever, plus scan showing that the maximal diameter of the abscess has reduced). If criteria are met, antibiotics are stopped; if not, oral antibiotics are continued, with reassessment for clinical response fortnightly. If criteria for clinical response are met by Week 12, the primary endpoint of clinical cure is met. A cost analysis will be performed to assess the cost saving of early conversion to oral antibiotics, and a quality of life analysis will be performed to assess whether treatment with oral antibiotics is less burdensome than prolonged IV antibiotics. DISCUSSION: Our results would help inform local and international practice guidelines regarding the optimal antibiotic management of Klebsiella liver abscess. A finding of non-inferiority may translate to the wider adoption of a more cost-effective strategy that reduces hospital length of stay and improves patient-centered outcomes and satisfaction. TRIAL REGISTRATION: Clinical trials gov NCT01723150.

Generic substitution, financial interests, and imperfect agency.

Policy makers around the world seek to encourage generic substitution. In this paper, the importance of prescribing physicians' imperfect agency is tested using the fact that some Swiss jurisdictions allow physicians to dispense drugs on their own account (physician dispensing, PD) while others disallow it. We estimate a model of physician drug choice with the help of drug claim data, finding a significant positive association between PD and the use of generics. While this points to imperfect agency, generics are prescribed more often to patients with high copayments or low incomes.

Cost effectiveness of three drugs for the treatment of S. aureus infections in Nigeria.

BACKGROUND: Resistance of microorganisms to existing antimicrobial agents threatens the effective utilization of available resources in sub-Saharan Africa. Cost-effective utilization of antibacterial agents is essential in effective health care delivery in Nigeria. OBJECTIVES: To determine the most cost effective antibacterial agent in the treatment of S. aureus infections in Lagos metropolis. SETTING: The study was carried out in a teaching hospital, a specialist hospital, a referral center and two private hospitals. METHODS: Cost effectiveness analysis of ciprofloxacin, cefuroxime and gentamicin identified to be most effective agent against 463 clinical isolates of S. aureus obtained from the five hospitals was carried out on the basis of societal, health care and third party perspectives using 'decision table" as an analytical model. Criteria considered in the model included degree of efficacy of the agents, adherence tendencies and tolerability. Both direct (cost of drugs, diagnosis/monitoring, personnel and transportation) and indirect (loss of productivity) costs were evaluated. MAIN OUTCOME MEASURES: These include economic outcome as total therapy cost, clinical outcomes as extent of antibacterial effectiveness obtained from degree of antibacterial efficacy, a proxy measurement of cure rates, and adherence tendency. Humanistic outcome was also measured as tolerability prorated from literature reported degree of adverse drug reactions events, risk of infection and pains from drug administration. RESULTS: Ciprofloxacin tablet is a dominant option and much more cost-effective than either cefuroxime or gentamicin in the treatment of S. aureus in Lagos. Regardless of the perspective of analysis, ciprofloxacin has the least cost effectiveness ratio of NGN4214.66 ($28.09), NGN2392.63 ($16.00) and NGN2048.66 ($13.65) from societal, health care and third party payer perspectives, respectively. Sensitivity analysis by increasing the effectiveness index of gentamicin injection-the least cost effective option to the value for the most cost effective option did not change the results. CONCLUSION: Ciprofloxacin should be used as first-line-treatment of S aureus in Lagos as it will lead to significant cost savings in the treatment of S. aureus infections.

Improving quinolone use in hospitals by using a bundle of interventions in an interrupted time series analysis.

The objectives of the present study were to determine the effects of multiple targeted interventions on the level of use of quinolones and the observed rates of resistance to quinolones in Escherichia coli isolates from hospitalized patients. A bundle consisting of four interventions to improve the use of quinolones was implemented. The outcome was measured from the monthly levels of use of intravenous (i.v.) and oral quinolones and the susceptibility patterns for E. coli isolates from hospitalized patients. Statistical analyses were performed using segmented regression analysis and segmented Poisson regression models. Before the bundle was implemented, the annual use of quinolones was 2.7 defined daily doses (DDDs)/100 patient days. After the interventions, in 2007, this was reduced to 1.7 DDDs/100 patient days. The first intervention, a switch from i.v. to oral medication, was associated with a stepwise reduction in i.v. quinolone use of 71 prescribed daily doses (PDDs) per month (95% confidence interval [CI] = 47 to 95 PDDs/month, P < 0.001). Intervention 2, introduction of a new antibiotic guideline and education program, was associated with a stepwise reduction in the overall use of quinolones (reduction, 107 PDDs/month [95% CI = 58 to 156 PDDs/month). Before the interventions the quinolone resistance rate was increasing, on average, by 4.6% (95% CI = 2.6 to 6.1%) per year. This increase leveled off, which was associated with intervention 2 and intervention 4, active monitoring of prescriptions and feedback. Trends in resistance to other antimicrobial agents did not change. This study showed that the hospital-wide use of quinolones can be significantly reduced by an active policy consisting of multiple interventions. There was also a stepwise reduction in the rate of quinolone resistance associated with the bundle of interventions.

Effect of generics on price and consumption of ciprofloxacin in primary healthcare: the relationship to increasing resistance.

BACKGROUND: The introduction of generic versions of drugs has often resulted in an increase in the consumption of the agents involved. In December 2001, generic ciprofloxacin was marketed in Denmark. Our objective was to evaluate, in a community setting, the effect of price on consumption of ciprofloxacin and on ciprofloxacin resistance in Escherichia coli urine isolates. METHODS: We conducted a retrospective ecological study collecting monthly national data on the number of marketed versions and primary healthcare (PHC) sales of ciprofloxacin during January 1995-December 2005. Data were compared with a median price per defined daily dose (DDD) of ciprofloxacin during September 1999-December 2005. Yearly PHC consumption data from seven Danish counties were compared with the antimicrobial resistance profiles of PHC E. coli urine isolates. RESULTS: During 2002, the number of marketed versions increased from 3 to 10, and the median price per DDD decreased by 53%. From 2002 to 2005, the total consumption of oral ciprofloxacin in PHC increased significantly from 0.13 DDD/1000 inhabitant-days to 0.33 DDD/1000 inhabitant-days. During the same period, the frequency of ciprofloxacin resistance increased by 200%. A statistically significant correlation was found between the consumption of ciprofloxacin and the ciprofloxacin resistance rate in E. coli urine isolates, independent of the introduction of generic ciprofloxacin. CONCLUSIONS: After the introduction of generic ciprofloxacin, a significant increase in the total consumption of oral ciprofloxacin in PHC was observed in Denmark. The increase in consumption was significantly correlated with ciprofloxacin resistance in E. coli obtained from urine isolates.

The costs of treatment of early and chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.

The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.

A prospective, controlled, randomized, non-blind, comparative study of the efficacy and safety of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in empirical therapy for febrile neutropenic patients.

BACKGROUND: Empirical antibiotic treatment for febrile neutropenia is well established. The best regimen is still controversial. The purpose of this study was to evaluate the efficacy, safety, and cost of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in neutropenic febrile patients. METHODS: Ninety-five patients with febrile neutropenia were included in a prospective, controlled, randomized, non-blind, comparative study. Patients were randomly assigned to one of the treatment groups (63 to the ceftriaxone/ciprofloxacin group and 32 to the ceftazidime/amikacin group) and evaluated as successes or failures according to defined criteria. Daily assessments were made of all patients and all adverse events were recorded. RESULTS: The overall incidence of documented infections was 45.9%: 24/47 (51.1%) in the ceftriaxone/ciprofloxacin group and 10/27 (37%) in the ceftazidime/amikacin group. There was a significant difference in clinical efficacy between the groups (p=0.011) at the end of therapy. The ceftriaxone/ciprofloxacin group had an overall incidence of resolution and improvement of 95.7% in comparison to 75% in the ceftazidime/amikacin group. Thirty-nine organisms were isolated, 26 (66.67%) gram-negative and 13 (33.33%) gram-positive. There was a low incidence of adverse events in both groups. CONCLUSION: The combination of a single, high dose of ceftriaxone plus ciprofloxacin daily was more effective than the standard combination of thrice daily ceftazidime plus amikacin with no significant adverse events in either group.

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.

[Cost-effectiveness of the treatment of acute and chronic rhinosinusitis at the IMSS]. / Costo-efectividad del tratamiento de rinosinusitis aguda y crónica en el IMSS.

INTRODUCTION: Rhinosinusitis is one of the more common diseases encountered in outpatient visits to health care. The objective of this study was to determine the most cost-effective antibiotic treatment for patients with acute (RSA) and chronic rhinosinusitis (RSC) that is available at the Mexican Institute of Social Security (IMSS). METHODS: Cost-effectiveness analysis of RSA and RSC treatment from an institutional perspective. Effectiveness outcome was defined as the percentage of cure. A decision tree with a Bayesian approach included the following therapeutic alternatives: ciprofloxacin, gatifloxacin, trimetoprim/sulfametoxazol (TMP/SMX), amoxicilin/clavulanic acid (AAC) and clindamicin. RESULTS: Treatment for RSA with AAC showed a mean cost per cured patient of $ 878 pesos. The remaining antibiotics had a higher cost per unit of success, and therefore the results showed that AAC was the best alternative considering this criterion. The therapy that showed a larger percentage of cured patients in RSC was clindamicin; however, the therapeutic alternative with the lowest cost per successful unit was the one based on ciprofloxacin, which dominates gatifloxacin and AAC. CONCLUSIONS: The most cost-effective alternative in the antibiotic treatment of patients with RSA was ACC while for RSC it was ciprofloxacin; sensitivity analysis showed the strength of the base study results.

Authorized generic drugs, price competition, and consumers' welfare.

The growing frequency of authorized generics has important implications for the welfare of prescription drug consumers. Authorized generic entry could affect the timing of generic entry, brand-name and generic prices, and generic penetration. We reviewed 1999-2003 data and found that generic entry in the absence of short-run exclusivity restrictions benefits consumers through lower short-run prices. We suggest that these benefits likely also result from authorized generics. We posit that long-run prices and shares are likely essentially unaffected by authorized generics and that potential costs to consumers from any delayed generic entry are likely small.

[Good clinical practices and inpatient antibiotics: optimization of fluoroquinolone switch therapy]. / Bon usage des antibiotiques: optimisation du relais per os des fluoroquinolones.

OBJECTIVE: Intravenous-to-oral switch therapy is strongly recommended in the medical literature. The aim of this study was to assess how we can improve fluoroquinolone switch therapy. METHODS: In this comparative prospective study, we analyzed 243 intravenous ciprofloxacin treatments and assessed the impact of promoting a switch to oral step-down therapy. RESULTS: This study found that switches from intravenous to oral therapy increased, mainly in medical wards, and led to significant savings in direct costs. DISCUSSION: Promoting switch therapy has improved clinical practices in antibiotic use and led to lower direct and probably indirect drug-related costs. CONCLUSION: Our findings will help define the role of switch therapy in improving clinical practices in inpatient antibiotic use.

An economic evaluation of two ototopical treatments for acute otitis media in tympanostomy tube patients.

OBJECTIVE: The goal of this research was to determine the cost-effectiveness of ciprofloxacin 0.3%/dexamethasone 0.1% (CD) otic suspension versus ofloxacin 0.3% otic solution (OFX) for treatment of acute otitis media in tympanostomy tube patients. METHODS: A decision-analytic model was used to emulate the ototopical treatment of acute otitis media in patients with tympanostomy tubes. The economic outcome was the cost per otorrhea-free day (OFD) achieved per episode of care. Three tiers of antimicrobial therapy were modeled, with each successive tier representing the retreatment of clinical failures from the preceding tier. First-tier therapy compared CD and OFX using outcome measures obtained from a randomized clinical trial (n = 599). Second-tier therapy modeled the use of amoxicillin/clavulanate (ACA) using outcome measures obtained from a physician survey and medical literature. Third-tier therapy was modeled as pathogen-specific and curative. It could follow one of three pathways: 1) intramuscular ceftriaxone; 2) oral fluconazole; or 3) hospitalization for intravenous antibiotics. Third-tier outcomes were based on a physician survey. Cost data were obtained from standard references and presented from a payer perspective. RESULTS: The expected therapeutic costs were 249.40 dollars for the CD pathway and 265.44 dollars for the OFX pathway. The estimated number of OFDs per episode of care was 25.88 for the CD pathway and 23.86 for the OFX pathway. The cost-effectiveness ratios for CD and OFX therapies were 9.64 dollars and 11.13 dollars per OFD, respectively. CONCLUSION: CD is both more effective and less costly than OFX for the treatment of acute otitis media in patients with tympanostomy tubes.

Doxycycline plus streptomycin versus ciprofloxacin plus rifampicin in spinal brucellosis [ISRCTN31053647].

BACKGROUND: The optimal treatment regimen and duration of the therapy is still controversial in spinal brucellosis. The aim of this study is to compare the efficacy, adverse drug reactions, complications and cost of ciprofloxacin plus rifampicin versus doxycycline plus streptomycin in the treatment of spinal brucellosis. METHODS: The patients diagnosed as spinal brucellosis between January 2002 to December 2004 were enrolled into the study. Patients were enrolled into the two antimicrobial therapy groups (doxycycline plus streptomycin vs. ciprofloxacin plus rifampicin) consecutively. For the cost analysis of the two regimens, only the cost of antibiotic therapy was analysed for each patient. RESULTS: During the study period, 31 patients with spinal brucellosis were enrolled into the two antimicrobial therapy groups. Fifteen patients were included in doxycycline plus streptomycin group and 16 patients were included in ciprofloxacin plus rifampicin group. Forty-two levels of spinal column were involved in 31 patients. The most common affected site was lumbar spine (n = 32, 76%) and involvement level was not different in two groups. Despite the disadvantages (older age, more prevalent operation and abscess formation before the therapy) of the patients in the ciprofloxacin plus rifampicin group, the duration of the therapy (median 12 weeks in both groups) and clinical response were not different from the doxycycline plus streptomycin. The cost of ciprofloxacin plus rifampicin therapy was 1.2 fold higher than the cost of doxycycline plus streptomycin therapy. CONCLUSION: Classical regimen (doxycycline plus streptomycin), with the appropriate duration (at least 12 weeks), is still the first line antibiotics and alternative therapies should be considered when adverse drug reactions were observed.

Optimizing treatment of antimicrobial-resistant Neisseria gonorrhoeae.

The increasing prevalence of ciprofloxacin-resistant Neisseria gonorrhoeae has required replacing inexpensive oral ciprofloxacin treatment with more expensive injectable ceftriaxone. Further, monitoring antimicrobial resistance requires culture testing, but nonculture gonorrhea tests are rapidly replacing culture. Since the strategies were similar in effectiveness (> 99%), we evaluated, from the healthcare system perspective, cost-minimizing strategies for both diagnosis (culture followed by antimicrobial susceptibility tests versus nonculture-based tests) and treatment (ciprofloxacin versus ceftriaxone) of gonorrhea in women. Our results indicate that switching from ciprofloxacin to ceftriaxone is cost-minimizing (i.e., optimal) when the prevalence of gonorrhea is > 3% and prevalence of ciprofloxacin resistance is > 5%. Similarly, culture-based testing and susceptibility surveillance are optimal when the prevalence of gonorrhea is < 13%; nonculture-based testing is optimal (cost-minimizing) when gonorrhea prevalence is > or = 13%.

The impact of a pharmacist-managed dosage form conversion service on ciprofloxacin usage at a major Canadian teaching hospital: a pre- and post-intervention study.

BACKGROUND: Despite cost containment efforts, parenteral (IV) ciprofloxacin appears to be overutilized at Vancouver General Hospital. In November 2003, the Pharmacist-managed intravenous to oral (IV-PO) Dosage Form Conversion Service was implemented, enabling autonomous pharmacist-initiated dosage form conversion for ciprofloxacin. This study evaluates characteristics of ciprofloxacin use prior to and following implementation of this conversion service. METHODS: This was a single-centre, two-phase (pre/post), unblinded study. Phase I occurred between November 12, 2002 and November 11, 2003 (365 days), and Phase II between November 12, 2003 and March 11, 2004 (120 days). All patients receiving ciprofloxacin IV during these periods were reviewed. The primary endpoint was IV:PO ciprofloxacin use ratio. Secondary endpoints were total number of ciprofloxacin doses, proportion of inappropriate IV ciprofloxacin doses, cost of therapy between phases, and estimated cost avoidance with the intervention. RESULTS: Two hundred ciprofloxacin IV treatment courses were evaluated (100 per phase). The IV:PO ciprofloxacin use ratio was 3.03 (Phase I) vs. 3.48 (Phase II). Total number of doses and ratio of IV to total doses across phases were similar (p = 0.2830). IV-PO ciprofloxacin conversion occurred in 27/100 (27%) of IV courses in Phase I and 23/100 (23%) in Phase II. Proportion of inappropriate ciprofloxacin IV doses decreased between Phases I and II (244/521 (47%) vs. 201/554 (36%) (p = 0.0005), respectively). Furthermore, the proportion of pharmacist-preventable inappropriate ciprofloxacin IV doses was reduced between Phases I and II (114/244 (47%) vs. 65/201 (32%) (p = 0.0026). Proportional cost avoidance associated with total inappropriate IV use was 7,172 Can dollars/16,517 Can dollars (43%) (in Canadian dollars) in Phase I vs. 6,012 Can dollars/17,919 Can dollars (34%) in Phase II (p = 0.001). Similarly, proportional cost avoidance associated with pharmacist-preventable inappropriate IV doses was reduced from 3,367 Can dollars/16,517 Can dollars (20%) in Phase I to 1,975 Can dollars/17,919 Can dollars (11%) in Phase II (p = 0.001). CONCLUSION: While overall utilization of ciprofloxacin remained unchanged and the proportion of IV to total doses was stable during the study period, the proportion of inappropriate IV doses and its associated costs appear to have declined subsequent to implementation of a Pharmacist-managed IV-PO Dosage Form Conversion Service. Such a program may be a beneficial adjunct in facilitating appropriate and cost-effective usage of ciprofloxacin.