Direct medical costs associated with using vancomycin in methicillin-resistant Staphylococcus aureus infections: an economic model

SUMMARY

Objectives: To quantify the direct medical costs associated with using vancomycin, as inpatient treatment, in methicillin-resistant Staphylococcus aureus infections, in four clinical indications: complicated skin and soft tissue infections (SSTI), bacteremia, infective endocarditis (IE), and hospital-acquired pneumonia (HAP).

Research design and methods: A decision-analytic model was constructed to evaluate the cost of administering intravenous vancomycin. Cost inputs included hospitalization, drug procurement, materials, preparation and administration, renal function and drug monitoring, treating adverse events, and treatment failure. Probabilities and lengths of stay and treatment were obtained from the literature, an antimicrobial therapy database and clinical expert opinion. Univariate and multivariate sensitivity analyses were conducted to confirm the robustness of the baseline scenario.

Main outcome measures: The cost of using vancomycin in the four indications, including and excluding hospital cost.

Results: Whereas the drug acquisition price of vancomycin 1?g is $9.01 per dose, when all costs associated with using vancomycin were included, the cost per dose rose to $29–$43 per patient. Total costs per patient receiving multiple doses in a single course of treatment, excluding hospital room costs, were for SSTI, bacteremia, IE, and HAP, $779, $749, $2261, and $768, respectively. Total costs, including hospital length of stay, were for SSTI $23?616, bacteremia $26?446, IE $48?925, and HAP $22?493. In univariate analyses varying per diem hospital costs and length of stay had the greatest impact. Results of the multivariate analysis were comparable to the costs in the baseline scenario for all indications.

Conclusions: This analysis highlights the importance of capturing all costs associated with using a drug and not simply focusing on drug acquisition cost. Future economic analyses should identify and account for the key cost burdens of a particular treatment to calculate its true cost.     

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.     

Direct medical costs associated with using vancomycin in methicillin-resistant Staphylococcus aureus infections: an economic model

OBJECTIVES: To quantify the direct medical costs associated with using vancomycin, as inpatient treatment, in methicillin-resistant Staphylococcus aureus infections, in four clinical indications: complicated skin and soft tissue infections (SSTI), bacteremia, infective endocarditis (IE), and hospital-acquired pneumonia (HAP). Research design and methods: A decision-analytic model was constructed to evaluate the cost of administering intravenous vancomycin. Cost inputs included hospitalization, drug procurement, materials, preparation and administration, renal function and drug monitoring, treating adverse events, and treatment failure. Probabilities and lengths of stay and treatment were obtained from the literature, an antimicrobial therapy database and clinical expert opinion. Univariate and multivariate sensitivity analyses were conducted to confirm the robustness of the baseline scenario. MAIN OUTCOME MEASURES: The cost of using vancomycin in the four indications, including and excluding hospital cost. RESULTS: Whereas the drug acquisition price of vancomycin 1g is US dollars 9.01 per dose, when all costs associated with using vancomycin were included, the cost per dose rose to US dollars 29-US dollars 43 per patient. Total costs per patient receiving multiple doses in a single course of treatment, excluding hospital room costs, were for SSTI, bacteremia, IE, and HAP,US dollars 779, US dollars 749, US dollars 2261, and US dollars 768, respectively. Total costs, including hospital length of stay, were for SSTI US dollars 23616, bacteremia US dollars 26446, IE US dollars 48925, and HAP US dollars 22493. In univariate analyses varying per diem hospital costs and length of stay had the greatest impact. Results of the multivariate analysis were comparable to the costs in the baseline scenario for all indications. CONCLUSIONS: This analysis highlights the importance of capturing all costs associated with using a drug and not simply focusing on drug acquisition cost. Future economic analyses should identify and account for the key cost burdens of a particular treatment to calculate its true cost.     

Daptomycin versus vancomycin for complicated skin and skin structure infections: clinical and economic outcomes

STUDY OBJECTIVE: To assess the effect of daptomycin compared with vancomycin on the clinical and economic outcomes in patients with complicated skin and skin structure infections. DESIGN: Prospective, open-label study. SETTING: Level 1 trauma center in Detroit, Michigan. PATIENTS: Fifty-three adult patients with complicated skin and skin structure infections at risk for methicillin-resistant Staphylococcus aureus (MRSA) infection who were treated with daptomycin and a matched cohort of 212 patients treated with vancomycin. INTERVENTION: Patients in the prospective arm received intravenous daptomycin 4 mg/kg every 24 hours for at least 3 days but not more than 14 days. Historical controls received at least 3 days of vancomycin dosed to achieve trough concentrations of 5-20 microg/ml. MEASUREMENTS AND MAIN RESULTS: Outcomes evaluated included blinded assessments of clinical resolution, duration of therapy, and costs. The most common diagnoses were cellulitis (31%), abscess (22%), and both cellulitis with abscess (37%). Microbiology differed significantly between groups, with S. aureus found in 27 patients (51%) in the daptomycin group and 167 patients (79%) in the vancomycin group and MRSA in 22 (42%) and 159 (75%), respectively (p<0.001). The proportions of patients with clinical improvement or resolution of their infections on days 3 and 5 were 90% versus 70% and 98% versus 81% in the daptomycin versus vancomycin groups, respectively (p<0.01 for both comparisons), and 100% at the end of therapy in both groups. Among patients with complete resolution of their infections (41 patients [77%] with daptomycin vs 89 patients [42%] with vancomycin, p<0.05), median duration of intravenous therapy was 4 and 7 days, respectively, (p<0.001), and hospital costs were $5027 and $7552 (p<0.001). CONCLUSIONS: Patients receiving daptomycin achieved more rapid resolution of symptoms and clinical cure and had a decreased duration of inpatient therapy compared with those receiving vancomycin. This study suggests that daptomycin is a cost-effective alternative to vancomycin for complicated skin and skin structure infections.     

Comparative costs of ertapenem and piperacillin-tazobactam in the treatment of diabetic foot infections.

PURPOSE: To evaluate potential cost savings, trial data were used to determine the clinical outcomes for i.v. ertapenem given once daily and i.v. piperacillin-tazobactam given every six hours daily in treating diabetic foot infections. METHODS: A cost-minimization analysis (CMA) was conducted on the drug-dosing data of the subset of patients enrolled in a recent double-blind randomized trial who were treated solely as inpatients and were clinically evaluable at fi nal assessment (n = 99). Cost per dose was calculated from (a) average hospital acquisition price per dose for ertapenem ($40.52) or piperacillin-tazobactam ($13.58), (b) average U.S. wages and benefits for labor, based on nine published time-and-motion studies of i.v. antibiotic preparation and administration ($3.10), and (c) consumable supplies, using a 40% discount off the manufacturer list price ($2.90). For each patient, the actual number of antibiotic doses given was multiplied by total cost per dose. RESULTS: There were no significant differences between antibiotic groups with respect to patient demographics, percentage with a severe wound, and mean days of i.v. therapy. Compared with piperacillin-tazobactam, patients treated with ertapenem received significantly fewer mean doses (25.5 versus 7.5; p < 0.0001) and lower antibiotic-related costs ($502.76 versus $355.55, respectively; p < 0.001). The $147.21 difference between groups accounts for approximately 3% of total hospital Medicare reimbursements for these infections. CONCLUSION: A CMA of treatment of diabetic foot infections showed that, compared with piperacillin-tazobactam given four times daily i.v., ertapenem given once daily i.v. was associated with lower drug acquisition and supply costs and less time and labor devoted to preparation and administration of i.v. therapy.     

Linezolid: a pharmacoeconomic review of its use in serious Gram-positive infections

Linezolid (Zyvox), the first available oxazolidinone antibacterial agent, has good activity against Gram-positive pathogens, including multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Randomised multicentre trials in patients with various types of serious Gram-positive infections showed that clinical cure rates with linezolid were similar to those with vancomycin or teicoplanin. In some subgroup analyses, which must be interpreted with a degree of caution, clinical advantages were noted for linezolid (e.g. versus vancomycin in confirmed MRSA nosocomial pneumonia and MRSA-complicated skin and soft tissue infections). Although generally well tolerated, gastrointestinal adverse effects are relatively common with linezolid and it has been associated with thrombocytopenia and myelosuppression. The oral bioavailability of linezolid is approximately 100%, thus allowing sequential intravenous-to-oral administration without changing the drug or dosage regimen. Healthcare resource use data from various countries indicate that this practical advantage translates into at least a trend towards reduced length of hospital stay compared with vancomycin, which may offset its several-fold higher acquisition cost. Modelled analyses from the US, despite some limitations, indicate that, compared with vancomycin, linezolid is associated with lower total hospitalisation costs for the treatment of patients with cellulitis and has a favourable incremental cost-effectiveness ratio of approximately US30,000 dollars per QALY gained (2001 value) for patients with ventilator-associated pneumonia. Broadly similar results have also been reported in modelled analyses from other countries. In conclusion, for patients with serious Gram-positive infections, including those caused by suspected or proven multidrug-resistant pathogens such as MRSA, linezolid is an effective and generally well tolerated therapeutic option. Linezolid is currently the only antibacterial agent with good activity against MRSA that can be administered orally (as well as intravenously). It may be particularly useful as an alternative to vancomycin in patients who have impaired renal function, poor or no intravenous access, require outpatient therapy, or who have been unable to tolerate glycopeptides. Healthcare resource use studies and pharmacoeconomic analyses generally support the use of linezolid in some subgroups of patients, although results should be interpreted with due consideration of the study limitations.     

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.     

Clinical experience of quinupristin-dalfopristin for the treatment of antimicrobial-resistant gram-positive infections

Data regarding clinical administration, outcomes, and costs of quinupristin-dalfopristin treatment in 48 patients with serious gram-positive infections in a large teaching hospital were analyzed retrospectively. Thirty-six patients had vancomycin-resistant Enterococcus faecium (VREF) infections, 10 had methicillin-resistant Staphylococcus aureus (MRSA) or Staphylococcus epidermidis (MRSE) infections, and 2 were treated empirically Overall, 67% of the patients were clinically cured, and 56% had bacteriologic eradication; overall response rate was 48%. Patients with VREF bacteremia had the highest clinical cure (82%) and bacteriologic eradication (73%) rates. Mortality rate was 31%, but 6 of 15 patients who died were treated successfully with quinupristin-dalfopristin. Length of hospital stay was significantly shorter among patients who lived versus those who died (p<0.05). Similarly, the mean hospital cost/patient was significantly lower in patients who lived than in those who died ($35,244 vs $122,922). Quinupristin-dalfopristin is effective in the treatment of both VREF and MRSA or MRSE infections in patients who fail to respond to, or are intolerant of, vancomycin.     

Cost analysis of 2 empiric antibacterial regimens containing glycopeptides for the treatment of febrile neutropenia in patients with acute leukaemia.

OBJECTIVE: Patients with cancer-associated neutropenia are at high risk of developing severe infections which can be fatal if treatment is not promptly administered. For this reason, fever is treated as soon as possible with broad spectrum antibacterial therapy. The objective of this study was to conduct a cost analysis in Italy comparing 2 empiric glycoprotein-containing antibacterial regimens for the treatment of febrile neutropenia in patients with acute leukaemia. DESIGN AND SETTING: A retrospective cost analysis was conducted, using the records of 527 febrile neutropenic patients with acute leukaemia who participated in an 18-month multicentre (29 Italian haematological units) randomised trial during 1991. All patients received either of the following 2 empiric intravenous regimens, each containing 3 antibacterial agents: ceftazidime (2 g, 3 times daily) and amikacin (15 mg/kg/day, in 3 separate doses) plus teicoplanin (6 mg/kg, in a single dose) or vancomycin (30 mg/kg/day, in 2 separate doses). Economic analyses were carried out from a hospital perspective. Only the direct costs per patient, i.e. mean antibacterial treatment and management cost, mean overall treatment failure cost and mean cost of adverse effects, were included. MAIN OUTCOME MEASURES AND RESULTS: No differences were found in the clinical response, defined as the improvement in the rate of fever or infection (if documented), between the 2 regimens. However, tolerability, defined as the incidence of adverse effects probably or definitely related to the assigned treatment, was reported to be better with the teicoplanin-rather than the vancomycin-containing regimen. CONCLUSIONS: Thus retrospective cost analysis showed that despite the higher acquisition cost of teicoplanin relative to vancomycin, the lower incidence of adverse effects associated with teicoplanin and its ease of administration (single daily dose) resulted in equivalent overall treatment costs between teicoplanin- and vancomycin containing regimens.     

Linezolid for the treatment of infections caused by Gram-positive pathogens in China

In this randomised, double-blind, comparator-controlled, multicentre study conducted in China, 142 hospitalised patients aged 18-75 years with pneumonia (n=80) or complicated skin and soft-tissue infection (cSSTI) (n=62) due to suspected or known Gram-positive pathogens were randomised (1:1) to receive either linezolid 600mg (n=71) or vancomycin 1g in patients aged 60 years (n=71) intravenously every 12h. The duration of treatment was 10-21 days for patients with pneumonia and 7-21 days for patients with cSSTI. Clinical outcomes were assessed at end-of-treatment (EOT) visit and follow-up (FU) visit 7-28 days post therapy. Staphylococcus aureus was the most common pathogen at baseline and most of these isolates were resistant to meticillin. All isolates were susceptible to linezolid and vancomycin. For the evaluable patients, the effective treatment rate for linezolid was higher than that for vancomycin at EOT (86.9% (53/61) vs. 61.7% (37/60)) and at FU (83.1% (49/59) vs. 64.9% (37/57)). Pathogen eradication rates for the microbiologically evaluable patients at FU were 79.2% (42/53) for linezolid and 61.5% (32/52) for vancomycin. The incidence of drug-related adverse events (AEs) was 25.4% (18/71) for linezolid and 16.9% (12/71) for vancomycin. Four (5.6%) linezolid-treated and eight (11.3%) vancomycin-treated patients discontinued the study drug because of an AE. Linezolid was well tolerated and effective for the treatment of infections caused by Gram-positive pathogens, including meticillin-resistant S. aureus.     

Cefuroxime axetil: an updated review of its use in the management of bacterial infections

Cefuroxime axetil, a prodrug of the cephalosporin cefuroxime, has proven in vitro antibacterial activity against several gram-positive and gram-negative organisms, including those most frequently associated with various common community-acquired infections. In numerous randomised, controlled trials, 5 to 10 days' treatment with oral cefuroxime axetil (250 or 500 mg twice daily) was an effective treatment in patients with upper (URTI) and lower respiratory tract infections (LRTI) as assessed by clinical and bacteriological criteria. The drug was as effective as several other cephalosporins, quinolones, macrolides and amoxicillin/clavulanic acid. Shorter courses (5 to 10 days') of cefuroxime axetil were at least as effective as a 10 day course. Furthermore, sequential therapy with intravenous cefuroxime (750 mg 2 or 3 times daily for 2 to 5 days) followed by oral cefuroxime axetil (500 mg twice daily for 3 to 8 days) proved an effective treatment in adult patients with community-acquired pneumonia (CAP). This approach provided similar efficacy to intravenous ampicillin/sulbactam followed by oral amoxicillin/clavulanic acid, a full parenteral course of cefuroxime, or intravenous then oral azithromycin or clarithromycin. Additionally, cefuroxime axetil was an effective treatment in patients with genitourinary, skin and soft-tissue infections, and erythema migrans associated with early stage Lyme disease. The drug is well tolerated by adult and paediatric patients, with adverse effects that are consistent with those of other cephalosporins. The majority of adverse events (primarily gastrointestinal disturbances) were mild to moderate in intensity and reversible upon discontinuation of treatment, with very few serious adverse events reported. Conclusions: Cefuroxime axetil is a broad spectrum antibacterial agent with a pharmacokinetic profile that permits convenient twice-daily administration. The drug is an effective and well tolerated treatment in patients with various infections, including otitis media, pharyngitis, sinusitis, CAP and acute exacerbations of chronic bronchitis. Cefuroxime axetil proved effective as a component of intravenous/oral sequential therapy in the treatment of CAP, although there are currently no dosage recommendations available for this regimen in some countries. Cefuroxime axetil may be considered as an empirical therapy for a range of community-acquired infections, including those in which beta-lactamase-producing strains of common respiratory pathogens are identified as the causative organisms. In an era of rapidly emerging bacterial resistance, empirical treatment with bacterial agents, potentially preventing the emergence of bacterial resistance to agents such as cefuroxime axetil may ensure the appropriate use of newer antibacterial agents, potentially preventing the emergence of bacterial resistance to these newer drugs.     

Topical fenticonazole in dermatology and gynaecology: current role in therapy

Fenticonazole is an imidazole derivative with a broad spectrum of antimycotic activity against dermatophytes and yeasts in in vitro and clinical studies. Fenticonazole exerts its unique antimycotic mechanism of action in the following three ways: (i) inhibition of the secretion of protease acid by Candida albicans; (ii) damage to the cytoplasmic membrane; and (iii) by blocking cytochrome oxidases and peroxidises. Fenticonazole has also been shown to exhibit antibacterial action, with a spectrum of activity that includes bacteria commonly associated with superinfected fungal skin and vaginal infections, and antiparasitic action against the protozoan Trichomonas vaginalis. Therefore, fenticonazole may be an ideal topical alternative to multi-agent treatment of mixed infections involving mycotic, bacterial, dermatophyte and/or Trichomonas spp.Open-label clinical studies show that fenticonazole, in different pharmaceutical preparations administered once or twice daily, is effective in the treatment of superficial mycoses of the skin. In particular, fenticonazole is very effective (often with 100% of patients achieving a negative mycological assay) in pityriasis versicolor and candidiasis. For example, a large (n = 760) study showed fenticonazole 2% cream, spray or powder to be associated with a mycological response in 100% of patients with pityriasis versicolor, 96.3% of those with tinea infections and 95.2% of patients with Candida infections. Comparative clinical studies show fenticonazole once or twice daily to be at least as effective as six different topical antimycotics (miconazole, clotrimazole, econazole, bifonazole, naftifine and cyclopyroxolamine) in the treatment of superficial mycoses of the skin. Intravaginal administration of fenticonazole is associated with a high rate of microbiological efficacy in patients with vaginal candidiasis, trichomoniasis, mixed infection and bacterial vaginosis. Intravaginal fenticonazole is at least as effective as clotrimazole and shows similar efficacy to miconazole in patients with vaginal candidiasis. Fenticonazole has a rapid onset of action and clinical efficacy is generally observed within days of commencing treatment.Topical fenticonazole is very well tolerated; adverse events are generally mild to moderate in severity and transient. The most frequent adverse events are burning sensation/cutaneous irritation and itch when applied to the skin. In a large, open-label study in superficial mycoses of the skin, the incidence of adverse events was <5% and these were rarely responsible for treatment discontinuation. Burning sensation is the most common adverse event seen with fenticonazole when administered intravaginally. However, this symptom of vaginal fungal infection was often present in patients prior to drug administration.Given the rising incidence of superficial fungal, and possibly mixed, infections, topical fenticonazole represents an important part of the topical antimycotic armamentarium.     

Linezolid: in infants and children with severe Gram-positive infections

Linezolid is an oxazolidinone antibacterial agent that has inhibitory activity against a broad range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. The systemic clearance and, therefore, the area under the plasma concentration-time curve and elimination half-life of linezolid change with increasing age in pediatric patients. With the exception of pre-term neonates aged <1 week, systemic clearance is more rapid in pediatric patients aged 0-11 years than in adolescents. The pharmacokinetic profile of linezolid is similar in adolescents and adults. Linezolid was as effective as vancomycin in the treatment of pediatric patients with Gram-positive infections (clinical cure rate 89.3% vs 84.5%), and as effective as cefadroxil in the treatment of children and adolescents with Gram-positive uncomplicated skin and skin structure infections (91.0% vs 90.0%) in the clinically evaluable population of two randomized, comparator-controlled trials. The clinical cure rate with linezolid was 92.4% in a noncomparative trial in hospitalized pediatric patients with community-acquired pneumonia. All patients with proven pneumococcal pneumonia were considered cured. Linezolid is generally well tolerated. The most common drug-related adverse events in the comparator-controlled trials were diarrhea, nausea, and headache; most events were mild to moderate in severity.     

Benefit-risk assessment of linezolid for serious gram-positive bacterial infections

Linezolid is an oxazolidinone, a new class of antibacterial with a unique mechanism of action, namely inhibition of the formation of a functional 70S initiation complex in the 50S bacterial ribosomal subunit. Linezolid is highly active against multidrug-resistant Gram-positive cocci, including meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate and vancomycin-resistant S. aureus, and vancomycin-resistant enterococci; its spectrum of activity also includes some anaerobic bacteria.Linezolid has been studied in several randomized controlled trials for the treatment of patients with community-acquired and nosocomial pneumonia, skin and soft tissue infections (SSTIs), urinary tract infections and bacteraemia. The available evidence suggests that linezolid is at least as effective as vancomycin for patients with nosocomial pneumonia, and there are some retrospective analyses supporting its superiority in comparison with vancomycin for MRSA nosocomial pneumonia, including ventilator-associated pneumonia. Linezolid is more effective than glycopeptides, macrolides and beta-lactams for SSTIs. The limited available data for the treatment of patients with bacteraemia suggest that it may be a better treatment option than vancomycin and beta-lactams for these patients, but questions have arisen regarding patients with catheter-related bacteraemias.Compared with other antibacterials, linezolid is associated with a greater frequency of adverse events, mainly nausea, vomiting, diarrhoea and headaches. Thrombocytopenia also occurs more frequently in patients taking linezolid but there is no increased frequency of anaemia. Other adverse events potentially related to linezolid therapy include fungal infections (moniliasis), hypertension and serotonin-like syndrome, tongue discolouration and taste alterations, dizziness, insomnia, rash and Clostridium difficile-related diarrhoea. The majority of adverse events develop after prolonged administration (i.e. >2 weeks) and subside shortly after discontinuation of linezolid. Peripheral or optic neuropathy, another possible adverse effect, is associated with an even longer duration of treatment (3-6 months).In conclusion, linezolid is an important treatment option for the treatment of patients with multidrug-resistant, Gram-positive bacterial infections. However, in order to reduce the possibility of development of resistance and preserve its activity, the use of linezolid should be restricted to treatment of patients with infections associated with high morbidity and mortality, particularly those caused by multidrug-resistant bacteria.     

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.     

Cefpodoxime proxetil. An appraisal of its use in antibacterial cost-containment programmes, as stepdown and abbreviated therapy in respiratory tract infections

Cefpodoxime proxetil is an orally administered prodrug which is converted in vivo to the third generation cephalosporin cefpodoxime. Cefpodoxime has a similar spectrum of antibacterial activity to the parenteral cephalosporins ceftriaxone and cefotaxime and a long elimination half-life, which allows once- or twice-daily administration. Cefpodoxime proxetil has proven efficacy in the treatment of community-acquired pneumonia and upper respiratory tract, skin and soft tissue and urinary tract infections. It has been evaluated for use in cost-containment programmes, as stepdown (parenteral-to-oral conversion) therapy in the treatment of community-acquired pneumonia and as abbreviated therapy in upper respiratory tract infections. Substituting oral for parenteral therapy can achieve considerable savings (in acquisition, delivery and labour costs). Moreover, oral administration has advantages for the patient in terms of comfort and mobility, avoids the hazards of parenteral delivery and may allow earlier discharge from hospital, or even allow home treatment from the outset in low-risk patients. As hospitalisation is usually the major cost component in treating serious infections, considerable savings can be made in this way. Pharmacy-driven stepdown programmes in 2 US hospitals have achieved cost savings by targeting patients with community-acquired pneumonia for early conversion from intravenous ceftriaxone therapy to oral cefpodoxime proxetil. Costs were compared with those from a control group of patients who continued to receive intravenous ceftriaxone until physicians deemed that oral therapy (with various agents) was appropriate. In one study, duration of parenteral therapy in the cefpodoxime proxetil group was reduced from 6.18 to 3.82 days and duration of hospitalisation was reduced from 10.06 to 6.23 days (p < 0.02), with corresponding hospitalisation cost reductions of $US7300 per patient. However, clinical trial data relating to the efficacy of cefpodoxime proxetil as stepdown therapy in patients initially requiring parenteral antibacterials are lacking. Abbreviated (4-to 7-day) cephalosporin regimens appear to be as effective as traditional 10-day penicillin regimens in the treatment of upper respiratory tract infections. Short regimens may improve patient compliance and tolerability, thereby reducing the costs of adverse effects and treatment failures. Data from preliminary clinical studies suggest that a 5-day course of cefpodoxime proxetil is as effective as an 8-day course of amoxicillin/clavulanic acid in treating either acute otitis media or sinusitis, and as effective as a 10-day course of amoxicillin/ clavulanic acid and more effective than a 10-day course of phenoxymethyl- penicillin in the treatment of pharyngotonsillitis. Cefpodoxime proxetil tended to be better tolerated and was associated with better compliance than penicillin-based regimens. Indeed, a pharmacoeconomic study showed that a 10-day regimen of cefpodoxime proxetil was associated with lower costs for treating adverse effects and treatment failures than a 10-day regimen of amoxicillin/clavulanic acid in the treatment of acute otitis media in children. A 5-day course of cefpodoxime proxetil had a lower cost per patient treated per month free of recurrence than a 10-day course of phenoxymethylpenicillin (non-generic) or amoxicillin/clavulanic acid in the treatment of recurrent pharyngotonsillitis. Thus, evidence to date suggests that cefpodoxime proxetil has potential for use as stepdown therapy in community-acquired pneumonia and in abbreviated therapy courses in upper respiratory tract infections. These preliminary observations require confirmation in well designed studies.     

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.     

Vancomycin vs teicoplanin in the treatment of Gram-positive infections: a pharmacoeconomic analysis in a Turkish University Hospital

OBJECTIVE: The aim of this study was to estimate and compare the costs of vancomycin and teicoplanin in the treatment of Gram-positive hospital infections in Turkey using a cost minimisation analysis. SETTING: Hacettepe University Hospital, Ankara, Turkey. METHOD: The health-care provider's perspective was considered within formal pharmacoeconomic assessment methodology. The records of 76 patients who had been hospitalised and treated for Gram-positive infections at Hacettepe University Hospital between 16 July 2003 and 22 November 2003 were retrospectively evaluated to obtain individual data on resources and associated costs. MAIN OUTCOME MEASURE: From a cost minimisation perspective, hospital directors may consider teicoplanin to be a relevant option in addition to vancomycin. RESULT: The estimated mean treatment cost per patient was 1,780 TRY (1,101 EUR) for teicoplanin and 1,429 TRY (884 EUR) for vancomycin, with statistical analysis failing to reveal any significant difference between the two drugs in terms of these total costs (p = 0.33). This cost minimisation analysis shows that the average costs of vancomycin and teicoplanin per patient observed did not differ significantly. CONCLUSION: Other potential advantages of one drug over the other, as reported by other authors, such as differing safety profiles or advantages in administration, may ultimately decide which is preferred.     

Cost implications of malpractice and adverse events

The ninth most common allegation against hospitals in 1989 was infection/contamination exposure, with the average claim costing nearly $34,000. Most malpractice claims are associated with inpatient surgery, according to 1990 statistics, and the average cost of a claim for infection and contamination related to surgery was over $64,000 in 1990. Physicians currently pay as much as $50,000 annually for malpractice insurance, and hospitals in some major metropolitan areas pay $8,000 per bed for insurance. An estimated 5% of hospitalized patients acquire nosocomial infections at an annual cost of approximately $10 billion. Prolonged hospitalization, usually for parenteral antibiotic treatment, accounts for more than three-fourths of this cost. To reduce the costs of malpractice, nosocomial infections can be prevented through infection-control programs, or damages can be reduced by treating infections with more efficacious and safer drugs that decrease the pain and suffering associated with the infection.     

Ertapenem: a review of its use in the management of bacterial infections

Ertapenem, a carbapenem antibacterial, has in vitro activity against many Gram- negative (including Enterobacteriaceae) and Gram-positive aerobic and anaerobic bacteria that are commonly associated with various infections.Once-daily parenteral (intravenous or intramuscular) ertapenem 1g was as effective as comparator antimicrobial agents (piperacillin/tazobactam or ceftriaxone +/- metronidazole) in patients with bacterial infections in randomised, double-blind, multicentre clinical trials. Response rates with ertapenem were 84% and 87% (combined microbiological and clinical) in patients with complicated intra-abdominal infections (CIAI), 82% (clinical) in patients with complicated skin and skin structure infections (CSSSI), 86% and 92% (microbiological) in patients with complicated urinary tract infections (CUTI), 92% (clinical) in patients with community-acquired pneumonia (CAP) associated with typical pathogens and 94% (clinical) in patients with acute pelvic infection. Respective response rates were statistically equivalent to those with comparators (81-94%). The efficacy of ertapenem was equivalent to that of piperacillin/tazobactam in patients infected with Enterobacteriaceae or anaerobes and to ceftriaxone in patients infected with Enterobacteriaceae. Ertapenem was generally well tolerated by patients with bacterial infections, with most adverse events being mild to moderate in severity. The most common ertapenem-associated adverse events were diarrhoea, infused vein complication, nausea, headache, vaginitis in females, phlebitis and/or thrombophlebitis and vomiting. CONCLUSION: Ertapenem is a broad-spectrum parenteral antibiotic with activity against many Gram-negative (including Enterobacteriaceae) and Gram-positive aerobic and anaerobic bacteria and is suitable for once-daily administration. Ertapenem has a role in the treatment of CAP associated with typical respiratory pathogens and is of particular value in the treatment of polymicrobial infections (such as CIAI, CSSSI, CUTI and acute pelvic infections), especially where Enterobacteriaceae and anaerobic bacteria are involved.