An Economic Evaluation of Sequential IV/po Moxifloxacin Therapy Compared to IV/po Co-amoxiclav With or Without Clarithromycin in the Treatment of Community-Acquired Pneumonia

doi:10.1378/chest.124.2.526

Chest

Volume 124, Issue 2, August 2003, Pages 526-535

https://doi.org/10.1378/chest.124.2.526 Get rights and content

Study objective

To evaluate costs, clinical consequences, and cost-effectiveness from a German and French health-care system perspective of sequential IV/po moxifloxacin monotherapy compared to co-amoxiclav with or without clarithromycin (AMC ± CLA) in patients with community-acquired pneumonia (CAP) who required parenteral treatment.

Methods

Costs and consequences over 21 days were evaluated based on clinical cure rates 5 to 7 days after treatment and health resource use reported for the TARGET multinational, prospective, randomized, open-label trial. This trial compared sequential IV/po monotherapy with moxifloxacin (400 mg qd) to IV/po co-amoxiclav (1.2 g IV/625 mg po tid) with or without clarithromycin (500 mg bid) for 7 to 14 days in hospitalized patients with CAP. Since no country-by-treatment interaction was found in spite of some country differences for length of hospital stays, resource data (antimicrobial treatment, hospitalization, and out-of-hospital care) from all centers were pooled and valued using German and French unit prices to estimate CAP-related cost to the German Sickness Funds and French public health-care sector, respectively.

Results

Compared to AMC ± CLA, treatment with moxifloxacin resulted in 5.3% more patients achieving clinical cure 5 to 7 days after therapy (95% confidence interval [CI], 1.2 to 11.8%), increased speed of response (1 day sooner for median time to first return to apyrexia, p = 0.008), and a reduction in hospital stay by 0.81 days (95% CI, − 0.01 to 1.63) within the 21-day time frame. Treatment with moxifloxacin resulted in savings of €266 and €381 for Germany and France respectively, primarily due to the shorter length of hospital stay. Cost-effectiveness acceptability curves show moxifloxacin has a ≥ 95% chance of being cost saving from French and German health-care perspectives, and higher probability of being cost-effective at acceptability thresholds up to €2,000 per additional patient cured.

Conclusion

IV/po monotherapy with moxifloxacin shows clinical benefits including increased speed of response and is cost-effective compared to IV/po AMC ± CLA in the treatment of CAP.

Section snippets

The TARGET Study

The TARGET study⁷ was a multinational, multicenter, randomized, open-label, phase III clinical trial designed to examine the safety and efficacy of sequential IV/po moxifloxacin compared to a standard regimen of sequential IV/po co-amoxiclav with or without clarithromycin (IV or oral). The study population was adult patients newly hospitalized with radiologic evidence of CAP and requiring initial parenteral therapy. Exclusion criteria included the presence of coexisting disease considered

Primary Clinical Outcomes

A total of 622 study patients with clinical signs and symptoms, including radiology, confirming the CAP diagnosis were included in the economic analysis. More than half of the patients had a diagnosis of severe CAP according to the 1993 American Thoracic Society criteria.²² The mean ages of patients in the moxifloxacin and AMC ± CLA groups were 55.2 years and 55.9 years, respectively; a total of 64.1% and 64.5% of patients were male, 28% and 29% had preexisting bronchopulmonary disease, and 59%

Discussion

Our study has presented the results of a cost-effectiveness analysis in which the difference in costs and outcomes of moxifloxacin vs a standard antimicrobial therapy, AMC ± CLA, has been assessed in the treatment of patients with CAP from the perspectives of health-care payers in Germany and France. We believe that the conduct of the economic study as an integral part of the TARGET clinical trial⁷ adds to the validity of the economic conclusions. Germany and France represent two important

ACKNOWLEDGMENT

The authors thank the following people for contributing to this study: Jacqueline Gough and Dan Pericak of Innovus Research Inc., Burlington, ON, for statistical analysis; Professor Gérard de Pouvourville, INSERM U 537, Le Kremlin Bicêtre, France, for advice on costing methods for France; Karine Séjean, of the Faculté de Médecine, Saint-Antoine, Paris, for costing of resource items for that country; and Felicitas Ku¨hne, a consultant to Innovus, for costing of resource items for Germany.

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Comparative analysis of length of stay, total costs, and treatment success between intravenous moxifloxacin 400 mg and levofloxacin 750 mg among hospitalized patients with community-acquired pneumonia
2009, Value in Health
This study aimed to evaluate the length of stay (LOS), costs, and treatment consistency among patients hospitalized with community-acquired pneumonia (CAP) initially treated with intravenous (IV) moxifloxacin 400 mg or IV levofloxacin 750 mg.
Adults with CAP receiving IV moxifloxacin or IV levofloxacin for ≥3 days were identified in the Premier Perspective comparative database. Primary outcomes were LOS and costs. Secondary outcomes included treatment consistency, which was defined as 1) no additional IV moxifloxacin or levofloxacin after ≥1 day off study drug; 2) no switch to another IV antibiotic; and 3) no addition of another IV antibiotic.
A total of 7720 patients met inclusion criteria (6040 receiving moxifloxacin; 1680 receiving levofloxacin). Propensity matching created two cohorts (1300 patients each) well matched for demographic, clinical, hospital, and payor characteristics. Before the patients were matched, mean LOS (5.87 vs. 5.46 days; P = 0.0004) and total costs per patient ($7302 vs. $6362; P < 0.0001) were significantly greater with moxifloxacin. After the patients were matched, mean LOS (5.63 vs. 5.51 days; P = 0.462) and total costs ($6624 vs. $6473; P = 0.476) were comparable in both cohorts. Treatment consistency was higher for moxifloxacin before (81.0% vs. 78.9%; P = 0.048) and after matching (82.8% vs. 78.0%; P = 0.002).
In-hospital treatment of CAP with IV moxifloxacin 400 mg or IV levofloxacin 750 mg was associated with similar hospital LOS and costs in propensity-matched cohorts.
Medico-economic aspects of pulmonology
2009, Revue des Maladies Respiratoires Actualites
Antibiotic therapy for community acquired Streptococcus pneumoniae pneumonia: clinical relevance of antibiotic resistance
2006, Medecine et Maladies Infectieuses
L'apparition de souches de Streptococcus pneumoniae de sensibilité diminuée aux β-lactamines et multirésistantes a peu modifié les recommandations d'antibiothérapies dans le cadre des pneumonies communautaires. Les raisons de ce faible impact clinique de ce phénomène microbiologique sont nombreuses : fréquence élevée de souches ayant une simple diminution de sensibilité aux β-lactamines mais très faible pourcentage de souches résistantes aux β-lactamines ; existence d'une relation complexe entre l'acquisition de résistance aux β-lactamines et une moindre virulence des souches de S. pneumoniae ; les modèles expérimentaux animaux de pneumonies bactériémiques létales à pneumocoque n'ont démontré qu'un ralentissement de la bactéricidie des β-lactamines, en particulier de l'amoxicilline, sur des souches résistantes et tolérantes. L'ensemble de ces données « préclinique » permet de comprendre la très faible influence de cette « résistance microbiologique » du pneumocoque aux β-lactamines dans le risque d'échec de la prise en charge d'une pneumonie à pneumocoque selon les schémas thérapeutiques actuels recommandés pour ces molécules. L'importance de la multirésistance, d'autant plus fréquente que les souches sont déjà résistantes aux β-lactamines, rend inutilisable en traitement probabiliste les macrolides. En revanche, la résistance aux fluoroquinolones (FQ) à visée antipneumococcique reste basse, inférieure à 3 %, de même pour les kétolides (< 1 %). Seule une vision stratégique globale d'utilisation de ces nouvelles molécules permettra de leur préserver une activité à long terme. La mortalité élevée des pneumonies à pneumocoques hospitalisées ne pourra être réduite qu'à travers une meilleure compréhension de la complexe relation hôte–bactérie.
The emergence of Streptococcus pneumoniae strains with reduced susceptibility to β-lactams and with multiple drug resistance has not led to major changes in recommendations for antibiotic therapy in patients with acute community-acquired pneumococcal pneumonia. Numerous factors explain the limited clinical impact of this major microbiological change. The frequency of intermediate strains is high but the frequency of resistant strains to β-lactams is very low. There is a complex relation between the acquisition of resistance to β-lactams and the decreased virulence of S. pneumoniae strains. The only finding in studies of humanized experimental animal models of lethal bacteremic pneumonia caused by resistance and tolerant strains was a slowing in the kinetics of β-lactams bactericidal activity, especially for amoxicillin. Taken together, this preclinical data shows that microbiological resistance of pneumococci to β-lactams has very little influence on a possible failure of recommanded treatment regimens for pneumococcal pneumonia. The high rate of multiple drug resistance, particularly among β-lactam resistant strains, rules out the probabilistic use of macrolides. Conversely, fluoroquinolone (FQ) resistance remains low, inferior to 3%, and the same is true for ketolides (< 1%). Only a global strategy of patient management in the use of these new drugs could ensure their long-term activity. The high mortality rate of hospitalized S. pneumoniae pneumonia will only be improved with a better understanding of the complex host–bacteria interactions.
Factors affecting cost of patients with severe community-acquired pneumonia in intensive care unit
2019, Turkish Thoracic Journal
Economic evaluation of community acquired pneumonia management strategies: A systematic review of literature
2019, PLoS ONE
Early clinical assessment of the antimicrobial activity of finafloxacin compared to ciprofloxacin in subsets of microbiologically characterized isolates
2018, Antimicrobial Agents and Chemotherapy

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: The current study was fully supported financially by Bayer and conducted by Innovus Research Inc., an independent contract research organization under the direction of Michael Drummond. Clinical outcomes were based on the report of the TARGET study designed and conducted by Bayer.

: Dr. Rolf Kubin, a clinician employed by Bayer and experienced in the treatment of CAP in Europe, provided input as required throughout the study. Analyses of cost and cost-effectiveness were conducted by Innovus Research Inc., and a project team including individuals from Innovus and Bayer reviewed the analysis plan, study report and manuscript, and agreed by consensus on final manuscript content.

: Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]).

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Chest

Clinical InvestigationsPNEUMONIAAn Economic Evaluation of Sequential IV/po Moxifloxacin Therapy Compared to IV/po Co-amoxiclav With or Without Clarithromycin in the Treatment of Community-Acquired Pneumonia*

Study objective

Methods

Results

Conclusion

Section snippets

The TARGET Study

Primary Clinical Outcomes

Discussion

ACKNOWLEDGMENT

Infect Dis Clin North Am

Chest

Respir Med

Community-acquired pneumonia

N Engl J Med

Community-acquired pneumonia: the annual cost to the National Health Service in the UK

Eur Respir J

Guidelines for management of adult community-acquired lower respiratory tract infections

Eur Respir J

Guidelines for the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy, and prevention

Am J Respir Crit Care Med

A randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community acquired pneumonia requiring initial parenteral treatment

Antimicrob Agents Chemother

Should clinical trials with concurrent economic analyses be blinded?

JAMA

Transferability of economic evaluation results

Estimating country-specific cost-effectiveness from multinational clinical trials

Health Econ

Rote Liste 2001. Arzneimittelverzeichnis fu¨r Deutschland [medication listing for Germany]

Die private Krankenversicherung. Zahlenbericht 1999/2000

Ministère de l’Emploi de la Solidarité, Paris. Programme de Médication des Systèmes d’Information (PMSI)

Gebu¨hrenordnung fu¨r A¨rzte (GOA¨)

Clinical Investigations
PNEUMONIA
An Economic Evaluation of Sequential IV/po Moxifloxacin Therapy Compared to IV/po Co-amoxiclav With or Without Clarithromycin in the Treatment of Community-Acquired Pneumonia^*