Pharmacoeconomic comparison of sequential IV/oral ciprofloxacin versus ceftazidime in the treatment of nosocomial pneumonia

A retrospective, cost-effectiveness analysis was performed on 106 clinically evaluable patients who participated in a multi-centre, randomized study of sequential IV/oral ciprofloxacin therapy versus ceftazidime for the treatment of nosocomial pneumonia. Although nearly half of the ciprofloxacin patients received sequential therapy, the majority were treated with a full IV regimen. Clinical success rates and antibiotic-related adverse events were similar for the ciprofloxacin and ceftazidime groups. Per patient and per day costs of antibiotic acquisition; preparation and administration; treatment of adverse events, and clinical failures were compared. Decision analysis revealed that ciprofloxacin therapy was cost-effective compared to ceftazidime 2 g q8h. Varying the probability of clinical success between 60-99% failed to change the economic decision; costs for ciprofloxacin were always lower than for ceftazidime. Further sensitivity analyses demonstrated that if the ceftazidime price was reduced by 50% (equivalent to 1 g q8h), treatment costs would be similar to ciprofloxacin therapy. Increasing the ciprofloxacin price by 50% (equivalent to a q8h frequency) produced per patient costs similar to ceftazidime, although ciprofloxacin therapy retained a lower cost per day (p < 0.0002). For the treatment of nosocomial pneumonia, ciprofloxacin therapy was cost-effective compared to ceftazidime.     

Oral ciprofloxacin: a pharmacoeconomic evaluation of its use in the treatment of serious infections

The broad spectrum of antibacterial activity and favourable pharmacokinetic profile of ciprofloxacin permit oral treatment of many serious infections which have traditionally necessitated parenteral antibacterial therapy. This has been demonstrated in comparative studies, in which ciprofloxacin was as effective and well tolerated as standard parenteral therapies (usually aminoglycoside/beta-lactam combinations or broad spectrum cephalosporins) in small numbers of patients with infections of the lower respiratory tract, urinary tract, skin and soft tissue, and bones and joints. Oral ciprofloxacin is considerably less expensive than most parenteral therapies, does not necessitate therapeutic drug monitoring and can be administered on an outpatient basis. In addition, administration by the oral route is more comfortable and convenient for the patient. Pharmacoeconomic studies have confirmed that substitution of oral ciprofloxacin for parenteral therapy in the treatment of serious infections can achieve considerable savings in drug acquisition costs, and labour and supplies associated with parenteral drug administration, and may allow early discharge from hospital, resulting in even greater savings. Mean reductions of 43 to 83% were achieved in antibacterial costs in 3 randomised prospective studies, when patients received oral ciprofloxacin instead of various parenteral agents, from the beginning of treatment, or after 3 days' parenteral therapy. It can be concluded that oral ciprofloxacin offers considerable scope for cost avoidance when appropriately substituted for parenteral therapy in the treatment of serious infections.     

Pharmacoeconomic Impact of Once-Daily Aminoglycoside Administration

A retrospective cost analysis compared hospital costs of standard gentamicin dosing and once-daily regimens in 1127 patients. Hospital costs compared were drug/supply/preparation/administration (DSPA; $4.56/500 mg once-daily dose and $3.32/100 mg every 8 hrs standard dose); therapeutic drug monitoring (TDM) ($25/gentamicin level); and nephrotoxicity management. The mean length of therapy was 4.5 days with both regimens. The mean number of blood samples drawn to measure drug levels was 0.65 for once-daily dosing and 1.7 for standard dosing. Mean DSPA and TDM costs/patient for a 4.5-day course of once-daily therapy were $20.52 and $16.25, respectively ($36.77/course of therapy). In comparison, estimated mean DSPA and TDM costs for 4.5 days standard therapy were $44.82 and $42.50, respectively ($87.32/course of therapy). We observed an overall reduction in nephrotoxicity from approximately 4% to 1.2% with the once-daily program, resulting in a nephrotoxicity management cost reduction from $182 to $55/patient exposed to aminoglycosides. The once-daily program resulted in a 58% reduction in aminoglycoside-associated hospital cost and a nephrotoxicity management savings of 70%/patient.     

A multicenter study of lomefloxacin versus ciprofloxacin in the treatment of complicated urinary tract infections

Lomefloxacin is a new difluorinated quinolone antimicrobial agent with broad antibacterial activity and a long half-life which allows once-daily dosing. A multicenter, randomized trial was conducted to compare the safety and efficacy of once-daily oral lomefloxacin with twice-daily oral ciprofloxacin in the treatment of complicated urinary tract infections (UTIs). All 203 patients enrolled in the study had significant bacteriuria of - 10(5) colony-forming units/ml (CFU/ml) and clinical signs and symptoms of UTI such as dysuria, frequency, urgency, pain, or hematuria. Patients were randomized to receive either 400 mg lomefloxacin once daily (n = 101) or 250 mg ciprofloxacin twice daily (n = 102). The predominant baseline pathogen isolated from the patients in both groups was Escherichia coli. At the third visit (5-9 days post-treatment), 97.8% of patients in the lomefloxacin group and 96.8% in the ciprofloxacin group showed satisfactory bacteriologic results. Clinical success was achieved in 98.9% of patients in both treatment groups and there were no statistically significant differences between the two groups. Both drug regimens were well tolerated and no patient discontinued treatment due to adverse events. It was concluded that once-daily lemofloxacin was as effective as twice-daily ciprofloxacin in patients with complicated UTIs.     

Ciprofloxacin extended release: in the treatment of urinary tract infections and uncomplicated pyelonephritis

Ciprofloxacin extended release (XR) is a new oral formulation of a fluoroquinolone that allows once-daily administration while maintaining therapeutic serum levels of the drug. The maximum plasma concentrations (Cmax) of once-daily ciprofloxacin XR 500 mg was higher than that of twice-daily ciprofloxacin immediate release 250 mg and the Cmax of once-daily ciproflocaxin XR 1000 mg was higher than that of twice-daily ciprofloxacin 500 mg. No accumulation of ciprofloxacin XR at steady state was observed in healthy men and all other pharmacokinetic parameters were similar to those of the immediate-release formulation. In patients with uncomplicated urinary tract infection (UTI), bacteriological eradication rates were similar in recipients of ciprofloxacin XR and immediate-release ciprofloxacin at the test-of-cure (TOC) visit, as were rates of persistence or new infection. Clinical cure rates were also similar in the two treatment groups. Bacteriological eradication occurred in 89% of ciprofloxacin XR and 85% of immediate-release ciprofloxacin recipients with complicated UTIs or acute uncomplicated pyelonephritis at the TOC visit. Clinical cure rates were also similar in the two treatment groups. black triangle Ciprofloxacin XR was generally well tolerated in patients with uncomplicated or complicated UTIs or acute uncomplicated pyelonephritis and showed similar tolerability to that of the immediate-release formulation.     

DUE of ciprofloxacin in the treatment of urinary tract infections in hospitalized patients

In this retrospective study of 30 patients with urinary tract infections, a drug usage evaluation indicated that 60% of the patient population sampled were appropriately switched to ciprofloxacin from IV antimicrobial agents; inappropriate use was identified in 40%. The drug's safety profile indicates that patients can be safely removed from IV antimicrobial therapy and continue treatment on ciprofloxacin, a measure which reduces treatment costs. These costs also can be lowered when inappropriate ciprofloxacin use is ruled out in patients with organisms sensitive to less costly oral antimicrobials. Identifying which patients should be removed from parenteral therapy maximizes the economic benefit of ciprofloxacin therapy and optimizes the impact of pharmacy intervention on patient care.     

Comparative analysis of drug distribution costs for controlled versus noncontrolled oral analgesics

Total costs for controlled substance oral analgesics and non-controlled analgesics were compared for patients at a 548-bed university hospital. During 1983, all cost elements involved in drug delivery (excluding large-volume parenterals) were identified. Direct and indirect pharmacy labor costs were determined. Personnel costs were calculated from time studies of nurses (in 1979-80) and pharmacy technicians (in 1982). Other pharmacy costs, based on the hospital's 1982 data, included inventory holding costs, computer services, supplies, and drug acquisition costs. Costs were calculated for four oral analgesics--acetaminophen with codeine, aspirin with codeine, ibuprofen, and zomepirac sodium--used during a 30-day period in 1981. For all medications, total average cost per dose for 1,949,418 doses was $2.44, of which 41% was drug acquisition cost. Personnel costs for pharmacy and nursing accounted for 43% and 11%, respectively, of total costs. For 46% of 5111 oral analgesic doses, frequency of administration was at least four times daily. Average purchase cost per dose for the oral analgesics was $0.15, while total costs for the controlled and non-controlled drugs were $1.02 and $0.50, respectively. For the four oral analgesics in this study, cost was affected by dosage schedule and controlled or noncontrolled status. Calculation of the total average cost per dose is useful in projecting annual costs and in identifying areas for cost reduction.     

Ceftriaxone. A pharmacoeconomic evaluation of its use in the treatment of serious infections

Ceftriaxone possesses a broad spectrum of antimicrobial activity that includes the Gram-positive and Gram-negative aerobes commonly associated with serious infections. Its therapeutic efficacy is comparable to that of other third-generation cephalosporins and aminoglycoside-combination regimens. The most commonly reported adverse events with ceftriaxone are similar in incidence and severity to those reported with other third-generation cephalosporins. Notably, the drug has a favourable pharmacokinetic profile which allows once-daily administration. In comparative studies with other parenteral regimens requiring 3 to 6 daily doses, treatment with once-daily ceftriaxone reduced total antimicrobial drug costs (i.e. acquisition, preparation and administration costs) by 17 to 52%. Ceftriaxone was also more cost effective than ceftazidime and a variety of other antimicrobial treatment regimens (penicillins, cephalosporins, combination regimens) in the treatment of patients with community-acquired pneumonia or bronchopneumonia. This reflected lower drug and hospitalisation costs associated with a reduced length of hospital stay in ceftriaxone recipients. In noncomparative studies, ceftriaxone achieved considerable hospitalisation cost savings in patients with serious infections (mostly bone, joint, skin/skin structure infections), who were able to receive all or part of their antimicrobial therapy as outpatients. In one analysis which evaluated all direct and indirect costs (such as training programmes, transportation, time for visits and supplies) and benefits (such as hospitalisation cost savings, return to work or school, increased productivity) of outpatient ceftriaxone therapy, the overall benefit-cost ratio was approximately 5:1. The studies to date confirm that ceftriaxone is effective, well tolerated, convenient to administer and, when utilised appropriately, offers the potential for cost avoidance in patients with serious infections. Although additional well designed pharmacoeconomic analyses are needed to further evaluate its cost effectiveness, ceftriaxone should be considered an essential third-generation cephalosporin formulatory representative in most clinical settings.     

Ciprofloxacin use under a reserved drug and stepdown promotion program

This study retrospectively evaluated the use of parenteral ciprofloxacin (PC) under the influence of a reserved antimicrobial drug program and an intravenous-oral stepdown program. During the first three months following its formulary introduction, 92 PC treatment courses were initiated. Fifty of these treatment courses in 49 adults were randomly selected for study. The hematology service accounted for 50% of the courses reviewed. The balance were initiated in the intensive care unit (16%), and six other services (34%). PC was used for the treatment of febrile neutropenia (50%), respiratory tract infections (20%), gram-negative sepsis (10%), and five other indications. Initial use of the intravenous formulation was considered appropriate in 92% of courses. Stepdown therapy occurred in 17 (34%) of treatment courses. Of the 26 patients considered candidates for oral therapy, seven patients (27%) were eligible for earlier stepdown and nine patients (35%) did not receive oral drug. According to our criteria, unnecessary use of the intravenous route occurred in 20% of PC treatment days. Mean total cost (acquisition plus delivery) of therapy per course was $668. This cost was higher in the hematology service (mean $990) than any other service (p = 0.0015). When stepdown therapy was employed the mean daily cost of therapy was $43.63 vs. $55.61 when the oral dosage form was not used (p = 0.04). Parenteral drug costs totalling $6245 were avoided by subsequent use of the oral dosage form. If full compliance with stepdown criteria had occurred, an estimated total savings of $10,769 could have been realized.     

Antibiotic therapy costs

The total cost of antibiotics, rather than acquisition costs alone was estimated. Preparation and administration costs, laboratory and monitoring costs, and labour costs are considered separately for the major antibiotics used within Christchurch Hospital. The oral route of antibiotic administration is by far the cheapest. The cost of infusion therapy compared with an IV push is considerable. This added about +15-+30 in equipment costs and another +20-+30 in labour costs and often constituted over 50% of the total cost of therapy. The cost of adverse reactions and differences in efficacy should ultimately be included but it was impossible to quantitate these factors in terms of absolute costs. Acquisition costs alone are a poor guide to the true costs of therapy. The cost of administering the drug should be considered in the contexts of efficacy, toxicity and impact on the environment. We contend that these considerations should be implied to the overall impact on the hospital budget, rather than the pharmacy costs alone.     

Evaluation of an antibiotic intravenous to oral sequential therapy program

AIM: This study was designed to analyse the drug consumption difference and economic impact of an antibiotic sequential therapy focused on quinolones. METHOD: We studied the consumption of quinolones (ofloxacin/levofloxacin and ciprofloxacin) 6 months before and after the implementation of a sequential therapy program in hospitalised patients. It was calculated for each antibiotic, in its oral and intravenous forms, in defined daily dose (DDD/100 stays per day) and economical terms (drug acquisition cost). At the beginning of the program ofloxacin was replaced by levofloxacin and, since their clinical uses are similar, the consumption of both drugs was compared during the period. RESULTS: In economic terms, the consumption of intravenous quinolones decreased 60% whereas the consumption of oral quinolones increased 66%. In DDD/100 stays per day, intravenous forms consumption decreased 53% and oral forms consumption increased 36%. CONCLUSIONS: Focusing on quinolones, the implementation of a sequential therapy program based on promoting an early switch from intravenous to oral regimen has proved its capacity to alter the utilisation profile of these antibiotics. The program has permitted the hospital a global saving of 41420 dollars for these drugs during the period of time considered.     

Potential cost savings of oral versus intravenous etoposide in the treatment of small cell lung cancer

An economic analysis was conducted on a randomised multicentre study comparing the use of intravenous (IV) etoposide versus oral etoposide treatment regimens in patients with small cell lung cancer. 41 patients received cisplatin 100 mg/m 2 intravenously (IV) on study day 1 and etoposide 120 mg/m 2 IV on study days 1, 2, and 3 (IV regimen); and 42 patients received cisplatin 100 mg/m 2 IV and etoposide 120 mg/m 2 IV on study day 1 and 240 mg/m 2 orally (equivalent to 120 mg/m 2 IV) on study days 2 and 3 (oral regimen). The results of the study from which these data were extracted showed equal efficacy between groups. Based on a retrospective review of resource use in the clinical trial, patient healthcare costs were examined in the following areas: antineoplastic drugs, IV fluids, supplies used for chemotherapy administration, and chemotherapy administration procedure fees. The total cost per course of therapy was $US2002 for the IV regimen and $US1653 for the oral regimen. This represented a 17% savings for patients receiving the oral regimen.     

A new ciprofloxacin stepdown program in the treatment of high-risk febrile neutropenia: a clinical and economic analysis

STUDY OBJECTIVE: To determine treatment outcomes and economic impact of a ciprofloxacin stepdown program for high-risk febrile neutropenic adults from the hospital's perspective. DESIGN: Unblinded, two-phase, single-center study. SETTING: Adult leukemia and stem cell transplant unit. PATIENTS: High-risk adults with febrile neutropenia. INTERVENTION: Two conditions were analyzed: a multidisciplinary ciprofloxacin stepdown program involving a reduction in parenteral ciprofloxacin dose from 400 to 200 mg (i.v.-i.v.) and conversion to oral ciprofloxacin (i.v.-p.o.) when criteria were met; and no i.v.-i.v. stepdown program. MEASUREMENTS AND MAIN RESULTS: Forty-six sequential treatment courses were compared with 42 treatment course from 6-month periods in preintervention (P1) and postintervention (P2) phases. Assessed parameters were clinical and microbiologic outcomes, adverse drug reactions (ADRs), and direct medical resource use and costs (1998 $Canadian) for the episode of febrile neutropenia. A decision analytic model was used to map probabilities and costs and to conduct sensitivity analyses. To supplement standard statistical testing, 1,000 bootstrap samples were created, and the mean cost difference was calculated between phases for each sample. Patient demographics, percentage i.v.-p.o. stepdown, and duration of therapy were similar between phases. Clinical success (83% P1, 81% P2), microbiologic eradication (15% P1, 24% P2), and possible ADRs (6% P1, 9% P2) did not differ. Intravenous-to-intravenous dose stepdown occurred in 33% of P2 and no P1 treatment courses (p<0.001). Resource use and costs were similar between phases, although a reduction was seen in the drug's mean total cost/day ($58 P1, $52 P2, p=0.04). There was also a trend toward a decrease in mean total treatment costs ($4,843 P1, $3,493 P2, p=0.08). In 1,000 bootstrap samples, 99.8% showed a cost advantage for P2. The model was robust to sensitivity analyses. CONCLUSION: This intervention influenced administration of ciprofloxacin without apparent compromise of patient outcomes and resulted in a reduction in total costs of treating febrile neutropenia.     

Cost effectiveness of oral triptan therapy: a trans-national comparison based on a meta-analysis of randomised controlled trials

OBJECTIVE: The objective of this study was to appraise the relative cost effectiveness of oral triptan therapy in the management of acute migraine, comparing the results obtained using drug cost data from six different countries, USA, UK, Canada, Germany, Italy and The Netherlands. METHOD: A meta-analysis of randomised placebo controlled trials of single dose oral triptans was carried out in order to calculate aggregate Numbers Needed to Treat (NNT) for each triptan and dose. Cost effectiveness ratios were then derived for each treatment by applying mean drug acquisition costs for each country to these NNTs. Using a graphical plot for each country, incremental cost effectiveness comparisons were then made versus sumatriptan 100 mg, the most commonly used oral triptan. RESULTS: When analysed in terms of 2-h pain one country to another. When compared to free outcomes, rizatriptan 10 mg and eletriptan 40 and 80 mg were the most effective oral triptans. Rizatriptan 10mg has the most advantageous absolute cost effectiveness ratio in all six countries studied, although levels of statistical significance compared to other agents varied from sumatriptan 100mg, rizatriptan 10 mg and eletriptan 40 mg are most consistently the cost effective treatment choices, both being cost dominant in five out of six countries studied. CONCLUSIONS: There are systematic differences in triptan efficacy that have an impact on treatment choice. Differences in pricing structure between countries mean that hierarchies of cost effectiveness will vary. Country-specific data should therefore be examined before defining treatment strategies.     

Drug formulations intended for the global market should be tested for stability under tropical climatic conditions

RATIONALE OBJECTIVE: The quality of drugs imported into developing countries having a tropical climate may be adversely affected if their formulations have not been optimized for stability under these conditions. The present study investigated the influence of tropical climate conditions (class IV: 40 degrees C, 75% relative humidity) on the drug content, in vitro dissolution and oral bioavailability of different formulations of two essential drugs marketed in Tanzania: diclofenac sodium and ciprofloxacin tablets. METHODS: Before and after 3 and 6 months storage under class IV conditions the drug content and in vitro dissolution were evaluated using United States Pharmacopoeia (USP) 24 methods. Following a randomized four-period cross-over study, the pharmacokinetic parameters of drug formulations stored for 3 months under class IV conditions were compared with those stored at ambient conditions. RESULTS: Drug content and drug release from all tested ciprofloxacin formulations were within USP-24 requirements and remained stable during storage at simulated tropical conditions. Oral bioavailability was also not influenced by tropical conditions. The dissolution rate of two diclofenac formulations (Diclo 50 manufactured by Camden and Dicloflame 50 manufactured by Intas) reduced significantly during storage under class IV conditions. After oral administration Camden tablets stored for 3 months under class IV conditions showed a reduction in C(max) (90% CI of C(max) ratio: 0.59 - 0.76). This reduction was smaller than expected based on the in vitro tests. CONCLUSIONS: Some drug formulations imported into Tanzania are not optimized for stability in a tropical climate. Manufacturers and regulatory authorities should pay more attention to the WHO recommendations for testing the stability of drugs under tropical climate conditions. Efforts should be made to improve the in vitro tests to better predict the bioavailability.     

Economic evaluation of oral ofloxacin versus standard parenteral therapy in the treatment of pneumonia

The purpose of this study was to examine how inpatient use of oral ofloxacin, a fluoroquinolone antibiotic, affects utilisation of healthcare resources in the treatment of pneumonia. We collected data via chart review from a recent multicentre trial that randomised hospitalised adult patients with pneumonia to oral ofloxacin or standard parenteral therapy of the investigators' choice. We followed a total of 126 patients from randomisation until rule-out of pneumonia, death, loss to follow-up, or 30 days following cure, whichever occurred first. For each patient, we collected data on all inpatient antibiotic usage, duration of stay in hospital, and the utilisation of selected healthcare services following discharge from hospital. While length of stay did not differ between ofloxacin and standard-therapy patients (9.2 vs 11.1 days, respectively; p = 0.28), the cost of inhospital antibiotic therapy for those who received ofloxacin was one-fifth that of patients who were randomised to parenteral therapy ($US47 vs $US268). Costs of outpatient antibiotic therapy were slightly higher for the group receiving ofloxacin ($US26 vs $US3). No difference was noted in the rate of hospital readmission during follow-up. Our study therefore suggests that the use of oral ofloxacin among inpatients with pneumonia reduces the costs of antibiotic treatment compared to standard parenteral therapy.     

Pharmacoepidemiology of ciprofloxacin: analysis of use patterns and cost impact

The pharmacoepidemiology and cost impact of ciprofloxacin use were evaluated after unrestricted availability in a 238-bed community teaching hospital. The medical records on all patients treated with oral ciprofloxacin over 6 months were reviewed. To determine if the availability of ciprofloxacin altered antibiotic usage patterns and outcome variables, a group of control patients from a period prior to ciprofloxacin availability were matched and compared to patients who had received the drug. Ciprofloxacin was used as both initial and replacement for parenteral therapy in a variety of infections. A successful clinical outcome was achieved in approximately 90% of patients treated with ciprofloxacin and resulted in an estimated cost avoidance of approximately $165/course. However, comparisons with the matched-control group revealed no differences in overall antibiotic costs or length of hospital stay. These results suggest that unrestricted availability of oral ciprofloxacin does not ensure changes in outcome variables related to cost. Educational and patient targeting programs may be necessary to promote earlier conversion of appropriate patients to newer oral therapies.     

Adverse testicular effects of some quinolone members in rats.

In the last few years, a marked decrease in male fertility has been reported. Environmental factors were recently suspected for this effect. Among those factors is the misuse of drugs and in particular antibiotics. Quinolones are a group of antibacterial agents with broad-spectrum activity. Testicular impairment of some quinolone members is controversial; a matter which stimulated our attention to investigate the adverse testicular effects of the most familiar quinolone members, namely: ofloxacin, ciprofloxacin and pefloxacin. They were given to rats in doses of 72, 135 and 72 mg kg(-1) day(-1) p.o., respectively, for 15 consecutive days. Ofloxacin was also used to establish a dose-response relationship in doses of 36, 72 and 360 mg kg(-1) day(-1) p.o. for 15 consecutive days. Results revealed that ofloxacin, ciprofloxacin and pefloxacin reduced testicular LDH-X activity by 39.8%, 62.7% and 60.7%, respectively. Moreover, sperm count, motility and daily sperm production were markedly decreased. Ofloxacin induced a dose-dependent decrease in testicular LDH-X activity, sperm count and motility. Furthermore, daily sperm production showed a marked reduction which amounted to 26.1% and 40. 0% following administration of ofloxacin (72, 360 mg kg(-1) day(-1) x 15 days), respectively. Moreover, administration of ofloxacin resulted in marked testicular histopathological changes. It is concluded that, ofloxacin, ciprofloxacin and pefloxacin significantly impaired both testicular function and structure in rats.