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Ceftriaxone

A Pharmacoeconomic Evaluation of its Use in the Treatment of Serious Infections

  • Pharmacoeconomic Drug Evaluation
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Summary

Synopsis

Ceftriaxolle possesses a broad spectrum of antimicrobial activity that indudes the Gram-positive and Gra-Negative aerobes commonly associated with serious infections. lts therapeutic efficacy is comparable to that of other third-generation cephalosporins and aminoglycoside-combinalion 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 pharcokinetic profile which allows once-daily administration.

In comparative studies with other parenteral regimens requiring 3 10 6 daily doses, treatment with once,daily ceftrioxone 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 regimem (penicillins, cephaosporins, combination regimens) in the treatment a 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 patients. 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 a administer and, when utilised appropriately, offers the potenial for cost avoidance in patients with serious infections. Although additional well designed pharmacoeonomic analyses are needed to further evaluate its cost effectiveness, ceftriaxone should be considered an essential third-generaion cephalolporin formulary, represetative in most clinical settings.

Diseose and Treatment Considerations

Treatment of serious infections traditionally requires hospitalisation and administration of intravenous antimicrobial agents. Besides hospitalisation costs, the major factors contributing toward the total direct costs of treatment include antimicrobial drug acquisition and administration costs, monitoring costs and costs arising from adverse effects or treatment failure. For some infections (e.g. osteomyelitis, skin/skin structure infections, bacterial endocarditis), clinically stable patients usually remain in hospital for extended periods of time solely to receive parenteral antimicrobials.

Ceftriaxone is a third-generation cephalosporin with a broad spectrum of activity in vitro which includes Gram-positive and Gram-negative aerobic and some anaerobic bacteria. Following parenteral administration of therapeutic dosages. ceftriaxone allains concentrations suffic ient to inhibit growth of the majority of bacteria in most body tissues and nuids. and has a plasma elimination half-life of around 8 hours. allowing once-daily administration.

Clinical trials havc shown that ceftriaxone is effective and well tolerated in eradicating susceptible bacteria in a wide range of serious infections, including those of the respiratory tract. blood. urinary tract, skin/skin structure. CSF, bone and joints. and infections in neutropenic patients. Data from comparative trials indicate that ceftriaxone is as effective as other third-generation cephalosporins and aminoglycoside/β-lactam combinations in treating serious infections in hospitalised patients. Like most other third-generation cephalosporins, ceftriaxone shou ld not be administered empirically in severe hospital-acquired infections of unknown aetiology if Pseudomonas aeruginosa is the suspected pathogen. Ceftriaxone has also demonstrated efficacy in treating adults and children with ostcomye litis, skin/skin structure infections. lower respiratory tract infections, urinary tract infections. infections in immunocompromised patients, bacteraemia and bacterial endocarditis in an outpatient setting (administered either entirely in the outpatient setting or after an initial period of hospitalisation).

Phormocoeconomic Benefits and Costs

The potential of ceftriaxone to save costs in hospitalised patients depends upon its comparable efficacy with other third-generation cephalosporins or combination regimens, and lower overall treatment costs as a result of its once-daily admi nistrat ion schedule. Preparation and administration costs and nursing time associated with once-daily administration of ceftriaxone are generally lower than those of antimicrobials which require mulliplc daily administrations.

The potential for the greatest cost avoidance may occur in patients who must remain hospitalised solely 10 receive parenteral antimicrobial treatment. With its convenient administration schedule, ceftriaxone offers the potential for significant cost avoid.mce in patients who are able to complete all or part of their antimicrobial regimen in an outpatient selling. The largest cost savi ngs will be realised in countries wi th national health insurance schemes or. in the US. in those institutions with a high proportion of prospective payment status patients. However, the lack of adequate insurance coverage or government restrictions related to outpatient administration of antimicrobials may be a deterrent for some patients.

Since ceftriaxone is generally well tolerated, the costs associated with adverse events are not expected to be significant, although studies which include these costs in their pharmacoeconomic analysis are needed to confirm this, Ceftriaxone monotherapy eliminates the costs associated with plasma drug concentration monitoring as well as the risk of additional costs incurred as a result of aminoglycoside toxicity.

Pharmocoeconomic Analyses

Cost-minimisation analyses in hospitali sed patients showed that once-daily ceftriaxone, when compared with antimicrobial regimens requiring 3 to 6 daily doses, reduced total antimicrobial drug COStS by 17 to 52% and saved approximately 40 min/day of nursing lime associated with parenteral therapy administration. In 3 comparisons in palients with community-acquired pneumonia, ceftriaxone was more cost effective than ceftazidime and a variety of other antimicrobial treatment regimens (penicillins, cephalosporins, combination regimens) as a result of lower drug and hospitalisation costs associated with a reduced length of hospital stay. However, the reliability of 2 of these studies was compromised by use of comparator agents which may not have provided adequate antibacterial activity for the treatment of community-acquired pneumonia: the refore more studies are needed before any definitive conclusions can be drawn about the effect of ceftriaxone treatment on the length of stay hospital.

Ceftriaxone offers a convenient administration schedule for parenteral therapy in outpatient settings. Charges associated with ceftriaxone outpatient treatment (emergency room visits, laboratory tests and hospitalisation) in febrile children with sickle cell disease were SUS 1195 lower per febrile episode than those associated with inpatient treatment. In noncomparative retrospective studies, significant hospitalisation cost savings (range $US4354 to $US7800 per patient) were realised when patients received some or all of their treatment with ccftriaxone as outpatients. A benefit-cost ratio of 5:1 was calculated for outpatient ceftriaxone treatment when costs associated with transponation, training programmes, supplies, time for outpatient visits. hospitalisation and increased productivity were evaluated.

In the outpatient studies discussed above, it was unclear how hospitalisation costs were determined and none of these analyses included costs of adverse effects or treatment failure. Thus, well designed comparative studies with other antimicrobials are needed 10 further facilitate the pharmacocconomic positioning of ceftriaxone in the outpatient setting.

Ceftriaxone is effective and well tolerated, and possesses a favourable pharmacokinetic profile which allows once-daily administration. Although the decision to grant formulary status to a particular third-generation cephalosporin should be based on institution-specific data regarding acquisition, administration and hospitalisation costs and antimicrobial susceptibilities, the available data suggests that ceflriaxone offers the potential for cost savings in the treatment of hospitalised patients and outpatients with serious infections.

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Davis, R., Bryson, H.M. Ceftriaxone. Pharmacoeconomics 6, 249–269 (1994). https://doi.org/10.2165/00019053-199406030-00009

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