Ceftaroline fosamil treatment outcomes compared with standard of care among hospitalized patients with complicated skin and soft tissue infections
Abstract
Aim: Compare clinical and cost outcomes associated with ceftaroline fosamil with other commonly used antibiotics in complicated skin and soft tissue infections. Methods: Retrospective analysis of hospital records from 2010 to 2013 in Premier’s Perspective comparative database for adults with complicated skin and soft tissue infection treated with intravenous ceftaroline fosamil, vancomycin, daptomycin, linezolid or tigecycline. Length of stay, inpatient costs and mortality were compared between propensity score-matched treatment groups. Results & conclusion: Compared with the other commonly used antibiotics, matched patients in the ceftaroline fosamil treatment group had an equivalent (1%) or lower (compared with linezolid, 2%) in-hospital mortality rate, and significantly lower (p < 0.001) average unadjusted and regression-adjusted length of stay and inpatient costs (savings of $3398.80 compared with daptomycin).
First draft submitted: 23 December 2015; Accepted for publication: 12 February 2016; Published online: 1 March 2016
Complicated skin and soft tissue infections (cSSTIs) are most commonly caused by Gram-positive bacteria including methicillin-susceptible Staphylococcus aureus (MSSA) but also methicillin-resistant S. aureus (MRSA) [1,2]. Most cases of cSSTI are mild to moderate in severity and may be treated with a variety of agents, but severe cases require hospitalization and parenteral therapy, representing a significant clinical treatment problem. An estimated 15 million cSSTIs, resulting in over 850,000 hospitalizations, occur each year in the USA [3].
Patients who are hospitalized often require coverage for resistant pathogens but with increasing antibiotic resistance the choice of empirical antibiotic treatment is becoming more difficult [1,2]. The mainstay of treatment for serious MRSA infections has until recently been the glycopeptides vancomycin and teicoplanin [4]. However, concern about the gradual development of resistance and concerns about efficacy [5] highlight the need for newer agents active against Gram-positive bacteria such as linezolid, daptomycin and tigecycline and ceftaroline fosamil, of which the latter two also include some Gram-negative coverage.
The economic impact of hospitalization associated with the increasing number of total MRSA infections is also a major concern and these resistant infections are known to prolong hospital length of stay (LOS) and increase total healthcare costs [6–8]. The mean LOS and cost of hospitalization for a patient with infections due to MRSA is 2.0- and 2.5-times more, respectively, than for patients with infections caused by MSSA [6,7] However, this is not the only burden when considering MRSA infection. Reports from some parts of the world, although not globally, of decreased susceptibility of S. aureus, including MRSA, to vancomycin and also the associated mortality and cost consequences of resistance, highlight the need for alternative antibiotics [9,10].
Ceftaroline, the active metabolite of Ceftaroline fosamil (Zinforo™, Teflaro™), is an oxyimino advanced-generation broad-spectrum cephalosporin which has in vitro activity against S. aureus and MRSA, both of which are associated with cSSTIs [11]. Ceftaroline fosamil has been found to be effective in the treatment of cSSTI in three Phase III trials – CANVAS 1 [12] (NCT00424190), CANVAS 2 [13] (NCT00423657), and COVERS [14] (NCT01499277) – which compared ceftaroline fosamil with vancomycin plus aztreonam for the treatment of cSSTI. In these studies ceftaroline fosamil was found to be noninferior to vancomycin plus aztreonam and was also effective against cSSTI caused by MRSA and other common cSSTI pathogens [15]. Ceftaroline fosamil was also well tolerated and had a safety profile concordant with other antibiotics in the cephalosporin class.
Since its approval in 2010 and commercial availability in the USA in 2011, retrospective studies describing the ceftaroline fosamil treatment of cSSTI in real world settings have reported clinical success rates between 81 and 86% when used as first- or second-line mono- or concurrent therapy [16,17]. However, real world studies comparing clinical and economic outcomes of ceftaroline fosamil with other commonly used antibiotics are not available. Here we assessed, using detailed retrospective data, differences in LOS, inpatient costs, and mortality among hospitalized patients with cSSTI who were receiving treatment with ceftaroline fosamil, compared with one of the four commonly used antibiotics – vancomycin (standard of care), linezolid, daptomycin and tigecycline.
Methods
This was a retrospective, observational, database study drawing on hospitalization records for adults aged 18 years and over with a diagnosis of cSSTI, identified using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes (Box 1). The study was conducted using the Premier Perspective comparative database (PPCD) from which data relevant to the period between 2010 and 2013 were extracted for analysis. The PPCD, believed to be the most comprehensive inpatient database in the USA consists of over 170 million patient records from approximately 500 hospitals. The PPCD database includes anonymized inpatient admission records with details on: admission and discharge dates, diagnosis and procedure codes, admission type, inpatient costs and charges (the cost was used in the analysis and extracted from the database as a single value per patient), drug use and routes of administration, and demographic and hospital characteristics.
Hospital records of patients receiving first-line (the initial treatment for cSSTI within the hospitalization episode for which the insurance claim was raised) intravenous (iv.) treatment with no more than one of the five antibiotics of interest (ceftaroline fosamil, vancomycin, daptomycin, linezolid or tigecycline) were included. Information regarding antibiotic therapy prior to cSSTI-related inpatient admission was not available. Patient records indicating more than one line of antibiotic therapy were not included in the study. Patient records of concomitant antibiotic therapy were included, but only when combined with a single antibiotic from the group of interest. Patient records with concomitant vancomycin and ertapenem use were included, but not those of vancomycin and daptomycin. Furthermore, all records indicating the use of oral vancomycin or oral linezolid therapy during the inpatient stay were excluded, as these may suggest more than one line of antibiotic therapy.
Cost per patient was extracted as a single value (the inpatient charge billed to the insurance company) as this was the only cost value uniformly reported in the database. This means that the costs assigned to a patient treated with one of the five antibiotics of interest may include a concomitant nonindex antibody therapy.
Demographic and hospital study measures extracted from the database were: age, sex, race, region, payer type, hospital bed size, teaching status and source and type of admission. Clinical characteristics were comorbidity burden (Charlson Comorbidity Index score) [18], presence of bacteremia and concomitant antibiotic use. Measures of hospital LOS (calculated using the admission and discharge date, assuming a full day on each end), inpatient costs (the total billed cost of a hospital stay after inpatient admission related to cSSTI, adjusted to US$2013 using the medical component of the Consumer Price Index) and in-hospital mortality were of primary interest.
Statistical analyses
Due to the observational, nonrandomized nature of the collected data we used the propensity score method (PSM) to match patient characteristics in the ceftaroline fosamil group with the other four antibiotic groups of interest. Here, the probability of antibiotic treatment in cSSTI patients is conditional to the baseline covariates. Prior to matching, differences in baseline covariates were compared among the comparison groups of interest using the t-test for continuous covariates and the χ2 test for categorical covariates. Following the prematching comparisons, four separate logistic regression models, with a generalized logit link, were used to estimate propensity scores for the following comparison groups: ceftaroline fosamil versus vancomycin, ceftaroline fosamil versus daptomycin, ceftaroline fosamil versus linezolid and ceftaroline fosamil versus tigecycline. Caliper matching with a maximal distance of 0.001 was used to match patients without replacement in their respective treatment groups using the estimated propensity scores such that patients nearest in the ceftaroline fosamil-treatment group were matched with patients in the vancomycin, daptomycin, linezolid and tigecycline treatment groups separately [19]. Following matching, using univariate tests (t-test and χ2), differences in baseline covariates were compared among the comparison groups to assess balance between the groups post matching. Outcomes with respect to mean LOS, inpatient costs and in-hospital mortality were compared between the four study groups using the unadjusted student’s t-test and covariate-adjusted generalized linear regression for LOS and inpatient costs and the χ2 test and Cox proportional hazard regression for in-hospital mortality.
Results
Baseline characteristics
Matched unadjusted covariate analysis
In the unmatched dataset, vancomycin (n = 418,435, used in 93.8% of patients) was the most commonly used antibiotic among patients with cSSTI followed by daptomycin (n = 13,161), tigecycline (n = 6631) and linezolid (n = 5067). Ceftaroline fosamil (n = 2834) was used in 0.6% of patients. Prior to propensity score matching, we observed some significant differences between ceftaroline fosamil and the other treatment groups in terms of demographic and hospital characteristics (Table 1). Notably, ceftaroline fosamil use was generally observed in a slightly more elderly population, with 41.3% of ceftaroline fosamil-treated patients aged 65 years or over compared with 36.1, 36.2, 39 and 37.9% of patients treated on admission with vancomycin, daptomycin, tigecycline and linezolid, respectively. Ceftaroline fosamil was more commonly prescribed to patients admitted from outpatient clinics (91.2%) compared with the alternative antibiotics considered (78.6–81.1%). A higher proportion of patients using ceftaroline fosamil had a discharge disposition of ‘transfer to homecare’ (81.1 vs 75.4, 75.3, 75.2 and 70% for the alternative antibiotics) compared with patients in the other antibiotic groups, potentially indicating a lower use of resources by the ceftaroline fosamil group.
Compared with patients treated with alternative antibiotics, those treated with ceftaroline fosamil demonstrated statistically significant (p < 0.001) higher rates of comorbidity in cases of obesity; skin ulcers; liver disease (with the exception of patients treated with daptomycin); and hypertension (with the exception of patients treated with tigecycline), and statistically significant (p < 0.001) lower rates of comorbidity in cases of diabetes (with the exception of patients treated with vancomycin and daptomycin) and hemiplegia (data not shown). Additionally, in the unmatched data ceftaroline fosamil-treated patients had statistically significant (p < 0.001) fewer coprescribed antibiotic medications (with the exception of patients treated with tigecycline) and duration of therapy was shorter (p < 0.001) than for the alternative antibiotics (with the exception of patients treated with vancomycin).
Logistic regression analysis
Matching of cohorts yielded balanced populations across the antibiotics selected on all demographic measures including age, sex, race, gender and treatment- and admission-characteristics. Most hospital characteristics were also balanced, with the exception of the ceftaroline fosamil and linezolid comparison group, which differed (p < 0.001) with respect to payer type, bed size and type of admission, as illustrated in Table 2.
The matching of cohorts also reduced differences in comorbidity rates across the comparison groups. A number of overall differences remained, notably ceftaroline fosamil treated patients had increased rates (p < 0.001) of skin ulcers, and significantly (p < 0.001) lower rates of diabetes (with the exception of patients treated with vancomycin [p = 0.045] and daptomycin [p = 0.077]) and hemiplegia compared with all other antibiotic comparison groups. Post matching, rates of congestive heart failure and hypertension were balanced across all treatment comparison groups with the exception of the ceftaroline fosamil–linezolid comparison group, which revealed ceftaroline fosamil patients having significantly (p < 0.001) lower rates of congestive heart failure and higher rates of hypertension (Table 3).
A shorter duration of antibiotic treatment was observed for ceftaroline fosamil-treated patients compared with patients treated with the alternative antibiotics, except in the case of vancomycin in which duration of ceftaroline fosamil therapy was longer than that of vancomycin (4.10 vs 3.85 days; p < 0.001).
In-hospital mortality, LOS & inpatient costs
Matched unadjusted covariate analysis
The average unadjusted LOS and inpatient costs were significantly (p < 0.001) lower among patients in the ceftaroline fosamil treatment group than among those in the vancomycin (mean LOS: 5.1 vs 5.6 days; costs: $8051 vs $10,089), daptomycin (LOS: 5.0 vs 6.3 days; costs: $7824 vs $10,227), tigecycline (LOS: 5.2 vs 6.1 days; costs: $8264 vs $11,353) and linezolid (LOS: 5.1 vs 6.4 days; costs: $8081 vs $12,020) treatment groups (data not shown).
Logistic regression analysis
The in-hospital mortality rate was approximately 1% for ceftaroline fosamil, vancomycin, tigecycline and daptomycin groups. In the case of the linezolid-treatment group mortality was 2% representing a significant difference between ceftaroline fosamil and linezolid-associated mortality rates (0.8 vs 2%; p = 0.0004) (Table 4).
Discussion
cSSTIs reportedly account for up to 10% of admissions to infection units in the USA [20] and in the UK [21]. The treatment costs for the management of SSTIs caused by S. aureus can be substantial but vary by factors such as populations studied, cost perspective and antibiotic therapy chosen [22,23]. A large study of Nationwide Inpatient Sample and Census Bureau data in 2009 reported the average associated cost of a S. aureus–SSTI hospitalization at $11,622 [24]. The difference in hospitalization costs associated with different study antibiotics varies according to the metrics being compared. For example daptomycin has been found to be a significant positive predictor of overall costs [23], likely due to lower costs of monitoring and hospitalization compared with vancomycin [25].
The very low number of patients in this large observational sample selected for ceftaroline fosamil therapy may reflect a reservation to use a new drug without empirical data (ceftaroline fosamil was approved in 2010 and became commercially available in the US in 2011). Of those treated, significantly lower inpatient costs and LOS were observed among patients prescribed ceftaroline fosamil as opposed to vancomycin or one of the other three commonly prescribed antibiotics. Additionally, mortality rates were comparable to or lower than (in the case of linezolid) the alternative antibiotics.
Historical metrics for LOS associated with cSSTIs in the USA are consistent with those observed in the current study: For example, a cohort of 900 patients showed median LOS of 5 days for hospital acquired infection and 4 days for community acquired infection [26]. Real world data on the management of cSSTIs in ten European countries, demonstrated longer average LOS (18.5 days ± 19.9) and higher but comparable mortality (3.4%) than observed in this cohort and may indicate differences in the patients studied or in healthcare service provision in Europe versus the USA [27]. Differences in comorbidities across treatment groups suggests that any further consideration of the current data would benefit from factoring in their effect on LOS, costs and mortality for the treatment of cSSTIs.
While a retrospective observational study using this very large PPCD database provides an opportunity for gaining insight into the usefulness of a newly licensed drug, the limitations inherent to this type of analysis may have led to a confounding of the relationship between the antibiotics of interest and the outcomes tested. Thus it is possible that many of the subjects who were treated with ceftaroline fosamil may have been systematically different from subjects given any of the other comparator agents in ways not measured by the variables included in the multivariable analysis. Specific circumstances that would strongly favour the use of ceftaroline fosamil include previous antimicrobial resistance to alternative agents, adverse reactions or risk of these reactions to alternative agents in a specific patient, failure of previously used therapies, need for simultaneous coverage of a second pathogen with a single intravenous drug and ease of use because of the lack of need for monitoring therapeutic levels (as needed for vancomycin). Furthermore, a precise comparison between the outcomes of the study is limited by possible unmeasured confounding variables, such as the possibility that ceftaroline fosamil-treated subjects may have been more likely to have successful therapy, because the drug would otherwise not be chosen to treat an cSSTI. A further limitation is that because the available data did not include admission time to discharge time in hours, LOS was calculated using the admission date to discharge date assuming a full day on each end. As a result, LOS is greater than duration of SSTI therapy, suggesting that patients waited a day before initiation of therapy, which is unlikely. It should also be noted that increased LOS reduces the overall impact of drug cost, thereby creating a bias toward more expensive drugs. An additional limitation was the lack of information available for complications of SSTIs, such as endocarditis, foreign body infection or osteomyelitis, as these may be confounders in the association of drug choice and measured outcomes.
Viewing this research as a pilot study, and bearing in mind its shortcomings, the wide differences between the number of patient records selected for ceftaroline fosamil-treated patients, which was only 0.6%, as opposed to those treated with alternative antibiotics, the current findings capture initial antibiotic prescribing practices of ceftaroline fosamil in the USA and provide a point of departure for further exploring its real-world effectiveness in comparison with other commonly used antibiotics for the treatment of cSSTIs.
Conclusion
This research serves as an initial step toward assessing outcomes associated with ceftaroline fosamil in treating cSSTIs in the real-world setting. In general, mortality associated with ceftaroline fosamil monotherapy treatment (1%) was similar to that in patients treated with vancomycin, daptomycin, and tigecycline but lower than that associated with linezolid (2%). However, significant reductions in LOS and inpatient costs were observed with ceftaroline fosamil treatment compared with other commonly used antibiotics in the management of cSSTI. Further, more detailed, research is required to examine the full clinical and economic impacts of alternative antibiotics for cSSTIs.
| Index antibiotic | p-value | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Characteristics | Ceftaroline fosamil | Vancomycin | Daptomycin | Tigecycline | Linezolid | Ceftaroline fosamil vs vancomycin‡ | Ceftaroline fosamil vs daptomycin‡ | Ceftaroline fosamil vs tigecycline‡ | Ceftaroline fosamil vs linezolid‡ |
| Population size (n) | 2834 | 418,435 | 13,161 | 6631 | 5067 | ||||
| Age (years): | |||||||||
| – Mean (SD) | 59.3 (17.9) | 57.5 (17.8) | 57.6 (17.2) | 58.6 (17.7) | 58.0 (17.9) | <0.0001 | <0.0001 | 0.1122 | 0.0027 |
| – Elderly (≥65 years); n (%) | 989 (41.3) | 151,022 (36.1) | 4761 (36.2) | 2589 (39) | 1918 (37.9) | <0.0001 | <0.0001 | 0.1267 | 0.0122 |
| Sex; n (%): | 0.1054 | 0.0011 | <0.0001 | 0.0002 | |||||
| – Male | 1264 (52.8) | 227,244 (54.3) | 6504 (49.4) | 3171 (47.8) | 2451 (48.4) | ||||
| Race; n (%): | <0.0001 | 0.5634 | 0.0729 | 0.0027 | |||||
| – Whites | 1815 (75.8) | 289,195 (69.1) | 10,093 (76.7) | 4936 (74.4) | 3704 (73.1) | ||||
| Region; n (%): | <0.0001 | <0.0001 | <0.0001 | <0.0001 | |||||
| – South | 1521 (63.5) | 171,328 (40.9) | 6908 (52.5) | 4513 (68.1) | 2901 (57.3) | ||||
| Payer type; n (%): | 0.0019 | <0.0001 | 0.1766 | <0.0001 | |||||
| – Private | 561 (23.4) | 102,298 (24.4) | 3705 (28.2) | 1594 (24) | 1204 (23.8) | ||||
| – Medicare/Medicaid | 1515 (63.2) | 258,600 (61.8) | 8303 (63.1) | 4276 (64.5) | 3413 (67.4) | ||||
| Bed size; n (%): | <0.0001 | <0.0001 | <0.0001 | <0.0001 | |||||
| – 0–199 | 398 (16.6) | 76,892 (18.4) | 1752 (13.3) | 1716 (25.9) | 1056 (20.8) | ||||
| – 200–399 | 1404 (58.6) | 160,656 (38.4) | 4963 (37.7) | 3059 (46.1) | 2277 (44.9) | ||||
| – 400+ | 594 (24.8) | 180,887 (43.2) | 6446 (49) | 1856 (28) | 1734 (34.2) | ||||
| Source of admission; n (%): | <0.0001 | <0.0001 | <0.0001 | <0.0001 | |||||
| – Outpatient | 2185 (91.2) | 328,906 (78.6) | 10,668 (81.1) | 5229 (78.9) | 3987 (78.7) | ||||
| Type of admission; n (%): | <0.0001 | <0.0001 | <0.0001 | <0.0001 | |||||
| – Emergency | 1536 (64.1) | 294,274 (70.3) | 7265 (55.2) | 3961 (59.7) | 3162 (62.4) | ||||
| Discharge status; n (%): | <0.0001 | <0.0001 | <0.0001 | <0.0001 | |||||
| – Died | 15 (0.6) | 4123 (1) | 118 (0.9) | 83 (1.3) | 112 (2.2) | ||||
| – Transferred to home care | 1944 (81.1) | 315,546 (75.4) | 9909 (75.3) | 4985 (75.2) | 3549 (70) | ||||
| – Transferred to other hospital | 380 (15.9) | 88,946 (21.3) | 2934 (22.3) | 1445 (21.8) | 1311 (25.9) | ||||
| – Not yet discharged | 0 (0) | 56 (0) | 1 (0) | 0 (0) | 1 (0) | ||||
| – Other | 44 (1.8) | 8773 (2.1) | 186 (1.4) | 112 (1.7) | 86 (1.7) | ||||
| – Unknown | 13 (0.5) | 991 (0.2) | 13 (0.1) | 6 (0.1) | 8 (0.2) | ||||
| CCI Score: | |||||||||
| – Mean (SD) | 4.57 (2.23) | 4.27 (2.33) | 4.35 (2.42) | 4.53 (2.41) | 4.59 (2.37) | <0.0001 | <0.0001 | 0.399 | 0.72 |
| CCI comorbidities§; n (%): | |||||||||
| – Congestive heart failure | 429 (15.1) | 56,510 (13.4) | 1940 (14.7) | 954 (14.4) | 829 (16.3) | 0.0087 | 0.5412 | 0.3399 | 0.1696 |
| – Chronic pulmonary disease | 660 (23.3) | 86,369 (20.6) | 2854 (21.6) | 1491 (22.5) | 1141 (22.4) | 0.0003 | 0.0498 | 0.3877 | 0.3966 |
| – Mild liver disease | 163 (5.7) | 18,736 (4.5) | 598 (4.5) | 251 (3.8) | 203 (4) | 0.0009 | 0.0054 | <0.0001 | 0.0004 |
| – Hypertension | 1276 (45) | 172,032 (40.9) | 5353 (40.5) | 2870 (43.2) | 2004 (39.4) | <0.0001 | <0.0001 | 0.1202 | <0.0001 |
| – Any tumor | 28 (1) | 7164 (1.7) | 208 (1.6) | 95 (1.4) | 90 (1.8) | 0.0032 | 0.0185 | 0.0805 | 0.0058 |
| – Skin ulcers/cellulitis | 2632 (92.8) | 323,113 (76.9) | 9279 (70.2) | 5401 (81.4) | 3900 (76.7) | <0.0001 | <0.0001 | <0.0001 | <0.0001 |
| – Moderate or severe liver disease | 29 (1) | 3494 (0.8) | 108 (0.8) | 63 (0.9) | 64 (1.3) | 0.2632 | 0.2806 | 0.7382 | 0.3497 |
| Duration of index antibiotic therapy; mean (SD) | 4.1 (2.75) | 3.95 (3.17) | 4.52 (4.25) | 4.62 (3.69) | 4.46 (3.79) | 0.0124 | <0.0001 | <0.0001 | <0.0001 |
| Other concomitant antibiotics; n (%) | 1986 (70.1) | 352,113 (84.2) | 10,398 (79.0) | 4482 (67.6) | 4173 (82.4) | <0.0001 | <0.0001 | 0.0172 | <0.0001 |
†Antibiotic received after inpatient admission related to complicated skin and soft tissue infection.
‡p-values based on student’s t-test for continuous measures and χ2 test for categorical measures.
§Selected CCI comorbidities are presented in this table.
CCI: Charlson Comorbidity Index; SD: Standard deviation.
| Propensity score matched cohorts | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Antibiotic groups | ||||||||||||
| Characteristic | Ceftaroline fosamil | Vancomycin | p-value‡ | Ceftaroline fosamil | Daptomycin | p-value‡ | Ceftaroline fosamil | Tigecycline | p-value‡ | Ceftaroline fosamil | Linezolid | p-value‡ |
| Population size (n) | 2834 | 2834 | 2651 | 2651 | 2606 | 2606 | 2554 | 2554 | ||||
| Age (years): | 0.7175 | 0.786 | Missing | 0.8818 | ||||||||
| – Mean (SD) | 59.3 (17.9) | 59.1 (17.9) | 59.4 (17.9) | 59.5 (17.6) | 59.5 (18.0) | 59.4 (17.8) | 59.0 (17.7) | 59.1 (17.8) | ||||
| Sex; n (%): | 0.8523 | 0.26 | 0.9779 | 0.3135 | ||||||||
| – Male | 1338 (47.2) | 1345 (47.5) | 1275 (48.1) | 1316 (49.6) | 1290 (48.7) | 1291 (48.7) | 1221 (46.1) | 1257 (47.4) | ||||
| Race; n (%): | 0.8026 | 0.0077 | 0.083 | 0.2615 | ||||||||
| – Whites | 2159 (76.2) | 2167 (76.5) | 2036 (76.8) | 2116 (79.8) | 2002 (75.5) | 2054 (77.5) | 1938 (73.1) | 1972 (74.4) | ||||
| Region; n (%): | 0.6603 | 0.0556 | 0.1346 | 0.1116 | ||||||||
| – South | 1769 (62.4) | 1785 (63.0) | 1656 (62.5) | 1723 (65.0) | 1706 (64.4) | 1757 (66.3) | 1573 (59.3) | 1628 (61.4) | ||||
| Payer type; n (%): | 0.9646 | 0.0114 | 0.3455 | 0.0022 | ||||||||
| – Private | 639 (22.5) | 637 (22.5) | 615 (23.2) | 619 (23.3) | 600 (22.6) | 583 (22.0) | 605 (22.8) | 569 (21.5) | ||||
| – Medicare/Medicaid | 1843 (65.0) | 1851 (65.3) | 1715 (64.7) | 1778 (67.1) | 1688 (63.7) | 1733 (65.4) | 1646 (62.1) | 1748 (65.9) | ||||
| Bed size; n (%): | 0.9492 | <0.0001 | 0.0012 | <0.0001 | ||||||||
| – 0–199 | 461 (16.3) | 470 (16.6) | 415 (15.7) | 555 (20.9) | 448 (16.9) | 491 (18.5) | 419 (15.8) | 524 (19.8) | ||||
| – 200–399 | 1650 (58.2) | 1644 (58) | 1531 (57.8) | 1293 (48.8) | 1508 (56.9) | 1377 (51.9) | 1485 (56) | 1283 (48.4) | ||||
| – 400+ | 723 (25.5) | 720 (25.4) | 705 (26.6) | 803 (30.3) | 650 (24.5) | 738 (27.8) | 650 (24.5) | 747 (28.2) | ||||
| Source of admission; n (%): | 0.8863 | 0.284 | 0.3981 | 0.924 | ||||||||
| – Outpatient | 2592 (91.5) | 2595 (91.6) | 2409 (90.9) | 2431 (91.7) | 2364 (89.2) | 2346 (88.5) | 2312 (87.2) | 2310 (87.1) | ||||
| Type of admission; n (%): | 0.9261 | 0.2332 | 0.1127 | 0.0003 | ||||||||
| – Emergency | 1826 (64.4) | 1840 (64.9) | 1683 (63.5) | 1697 (64) | 1676 (63.2) | 1728 (65.2) | 1613 (60.8) | 1658 (62.5) | ||||
| Duration of index antibiotic therapy, mean (SD): | 4.10 (2.75) | 3.85 (3.04) | 0.0011 | 4.12 (2.77) | 4.35 (3.88) | 0.0145 | 4.12 (2.74) | 4.59 (3.57) | <0.0001 | 4.13 (2.81) | 4.34 (3.35) | 0.0158 |
| Other concomitant antibiotics; n (%) | 1986 (70.1) | 1993 (70.3) | 0.8389 | 1895 (71.5) | 1865 (70.4) | 0.3643 | 1815 (69.6) | 1837 (70.5) | 0.5058 | 1935 (75.8) | 1947 (76.2) | 0.6942 |
†Propensity scores were estimated using four separate logistic regression models with a generalized logit link. The caliper (0.001) matching method was used to match patients in the ceftaroline fosamil group with patients in vancomycin, linezolid, tigecycline and daptomycin cohorts.
‡p-values based on student’s t-test for continuous measures and χ2 for categorical measures.
SD: Standard deviation
| Antibiotic group | Ceftaroline fosamil (n = 2834) | Vancomycin | p-value‡ | Ceftaroline fosamil | Daptomycin | p-value‡ | Ceftaroline fosamil | Tigecycline | p-value‡ | Ceftaroline fosamil | Linezolid | p-value‡ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Population size (n) | 2834 | 2834 | 2651 | 2651 | 2606 | 2606 | 2504 | 2504 | ||||
| CCI score: mean (SD) | 4.57 (2.23) | 4.57 (2.31) | 0.9488 (NS) | 4.55 (2.23) | 4.56 (2.47) | 0.8562 (NS) | 4.57 (2.22) | 4.60 (2.40) | 0.6062(NS) | 4.55 (2.23) | 4.62 (2.39) | <0.0001 |
| CCI comorbidities, n (%) (significantly different) | ||||||||||||
| Mild liver disease | 147 (5.8) | 85 (3.3) | <0.0001 | |||||||||
| Diabetes | 992 (38.1) | 1121 (43) | 0.0003 | 954 (37.4) | 1082 (42.4) | 0.0003 | ||||||
| Depression | 344 (12.1) | 440 (15.5) | 0.0002 | |||||||||
| Hypertension | 1140 (44.6) | 1005 (39.4 | 0.0001 | |||||||||
| Hemiplegia | 54 (1.9) | 95 (3.4) | 0.0007 | 51 (1.9) | 105 (4) | <0.0001 | 51 (2) | 108 (4.1) | <0.0001 | 51 (2) | 132 (5.2) | <0.0001 |
| Skin ulcers/cellulitis | 2631 (92.8) | 2268 (80) | <0.0001 | 2456 (92.6) | 2001 (75.5) | <0.0001 | 2413 (92.6) | 2154 (82.7) | <0.0001 | 2362 (92.5) | 2034 (79.6) | <0.0001 |
| Obesity | 798 (28.2) | 604 (21.3) | <0.0001 | 740 (27.9) | 601 (22.7) | <0.0001 | 731 (28.1) | 630 (24.2) | 0.0014 | 720 (28.2) | 598 (23.4) | <0.0001 |
| Bacteremia | 24 (0.8) | 84 (3) | <0.0001 | 24 (0.9) | 144 (5.4) | <0.0001 | 22 (0.9) | 63 (2.5) | <0.0001 | |||
| CCI comorbidities, n (%) (not significantly different) | ||||||||||||
| Congestive heart failure | 376 (14.7) | 447 (17.5) | 0.0069 | |||||||||
| Peripheral vascular disease | 323 (12.4) | 389 (14.9) | 0.0078 | |||||||||
| Ulcer disease | 8 (0.3) | 23 (0.8) | 0.0069 | 7 (0.3) | 24 (0.9) | 0.0022 | ||||||
| Mild liver disease | 145 (5.5) | 105 (4) | 0.0096 | |||||||||
| Diabetes | 996 (37.6) | 1097 (41.4) | 0.0045 | |||||||||
| Use of warfarin | 309 (11.7) | 376 (14.2) | 0.0061 | |||||||||
| Diabetes with end-organ damage | 250 (9.6) | 315 (12.1) | 0.0038 | |||||||||
| Any tumor | 28 (1) | 57 (2) | 0.0015 | 26 (1) | 48 (1.8) | 0.01 | 25 (1) | 37 (1.4) | 0.1252 | 22 (0.9) | 44 (1.7) | 0.0064 |
†Propensity scores were estimated using four separate logistic regression models with a generalized logit link. The caliper (0.001) matching method was used to match patients in the ceftaroline fosamil group with patients in vancomycin, linezolid, tigecycline and daptomycin cohorts.
‡p-values based on student’s t-test for continuous measures and χ2 test for categorical measures.
CCI: Charlson Comorbidity Index; SD: Standard deviation.
| Propensity score matched cohorts | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Antibiotic groups | ||||||||||||
| Characteristic | Ceftaroline fosamil | Vancomycin | p-value | Ceftaroline fosamil | Daptomycin | p-value | Ceftaroline fosamil | Tigecycline | p-value | Ceftaroline fosamil | Linezolid | p-value |
| In-hospital mortality; n (%): | 0.3248 | 0.1779 | 0.3742 | 0.0004 | ||||||||
| – Died | 22 (0.8) | 29 (1) | 18 (0.7) | 27 (1) | 20 (0.8) | 26 (1) | 21 (0.8) | 51 (2) | ||||
| – Alive | 2812 (99.2) | 2805 (99) | 2633 (99.3) | 2624 (99) | 2586 (99.2) | 2580 (99) | 2533 (99.2) | 2503 (98) | ||||
| Length of stay (days); mean (SD) | 5.08 (4.48) | 5.6 (5.18) | <0.0001 | 5.12 (4.56) | 6.43 (7.22) | <0.0001 | 5.02 (4.35) | 6.27 (6.3) | <0.0001 | 5.21 (4.63) | 6.08 (5.96) | <0.0001 |
| Inpatient costs ($); mean (SD): | ||||||||||||
| – Overall inpatient admissions costs | 8051.40 (8585.00) | 10,089.10 (12719.40) | <0.0001 | 8081.00 (8773.90) | 12,019.80 (18,855.00) | <0.0001 | 7824.10 (8331.40) | 10,277.50 (15,190.60) | <0.0001 | 8263.90 (8868.10) | 11,352.70 (14,814.10) | <0.0001 |
| – Per day inpatient costs | 1630.10 (861.70) | 1807.40 (1180.20) | <0.0001 | 1615.60 (854.60) | 1959.90 (1864.10) | <0.0001 | 1605.70 (863.70) | 1693.70 (1620.60) | <0.0001 | 1630.00 (870.80) | 1868.90 (1264.90) | <0.0001 |
| – Costs associated with index antibiotic treatment ($); mean (SD) | 434.40 (579.00) | 142.10 (216.40) | <0.0001 | 432.80 (585.60) | 1688.50 (8404.50) | <0.0001 | 423.80 (575.20) | 720.30 (737.00) | <0.0001 | 435.40 (595.50) | 843.50 (972.10) | <0.0001 |
†Antibiotic-received post complicated skin and soft tissue infection related inpatient admission.
Infection due to device or graft: 996.6x
Surgical site infection: 998.5x, 999.3x
Nonhealing surgical wound: 998.83
Decubitis ulcer: 707.x
Skin and subcutaneous tissue infections: 686.x
Erysipelas: 35
Carbuncle and furuncle: 680.x
Cellulitis and abscess of finger and toe: 681.x
Other cellulitis and abscess: 682.x
Acute lymphadenitis: 683
Pilonidal cyst with abscess: 685
Other local infections of skin and subcutaneous tissues: 686.x, except 686.1
Chronic ulcer of skin: 707.x
Abrasion or friction burn with infection: 910-917.1, 919.1
Blister, infected: 910-917.3, 919.3
Insect bite, nonvenomous, infected: 910-917.5, 919.5
Superficial foreign body, infected: 910-917.7, 919.7
Other superficial injury of specified site, infected: 910-917.9, 919.9
Post-traumatic wound infection: 958.3
Amputation stump infection (chronic): 997.62
Infection due to other internal vascular device, implant, and graft (excludes central lines): 996.62
Diabetes foot infection: 250.7x plus 681.10, 682.6, 682.7, 707.10-707.19, 785.4, 891.1, 891.2, 892.1, 892.2, 893.1, 893.2, 894.1, 894.2.
Osteomyelitis: 730.xx
Cellulitis and decubitus ulcers, ulcers of the skin: 680.xx, 681.xx, 682.xx, 683, 684, 685.0, 685.1, 686.1, 686.8, 686.9,709.4, 728.0, 729.3, 729.30, 729.39, 707, 707.0, 707.0x, 707.1, 707.8-707.15, 707.19
Trauma- or surgery-related: 872.xx-875.xx, 876.0, 876.1, 877.0, 877.1, 878.xx-887.xx, 890.xx-897.xx, 910.1, 910.3, 910.7, 910.9, 911.1, 911.3, 911.7, 911.9, 912.1, 912.3, 912.7, 912.9, 913.1, 913.3, 913.7, 913.9, 914.1, 914.3, 914.7, 914.9, 915.1, 915.7, 915.9, 916.1, 916.7, 916.9, 917.1, 917.3, 917.5, 917.7, 917.9, 919.3, 919.7, 958.3, 996.6, 996.60, 996.62, 996.66, 996.69, 997.62, 998.51, 998.59
Other serious skin infections: 040.0, 728.86, 729.4, 940.x- 949.x
Ceftaroline fosamil was approved in the USA in 2010 for the treatment of complicated skin and skin structure infections (cSSTIs) and became commercially available in the USA in 2011.
Real world studies demonstrate clinical success rates between 81 and 86% when used as first- or second-line mono- or concurrent therapy for cSSTIs but real-world clinical and health economic outcomes compared with other frequently used antibiotics are unknown
This retrospective study of hospital records from 2010 to 2013 compared clinical and cost outcomes associated with ceftaroline fosamil with other commonly used antibiotics in cSSTIs.
Compared with the other commonly used antibiotics, propensity score matched patients in the ceftaroline fosamil treatment group had lower (p < 0.001) average unadjusted length of stay and inpatient costs and a similar in-hospital mortality rate (∼1%).
Limitations of administrative claims data such as potential misclassification due to coding errors, missing data, limited clinical information and attrition bias should be considered in interpreting the study findings.
Financial & competing interests disclosure
This work was funded by AstraZeneca (AZ). S Karve and J Hackett are current employees of AZ. J Levinson was an employee of AZ at the time of conduct of this study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Medical writing support was provided by E Gibson and A Battersby, who are employed by Wickenstones Ltd, who were supported by AZ to complete this study and assist with the writing of the manuscript.
Open access
This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
References
Papers of special note have been highlighted as: • of interest
1.
Pollack CV, Amin A, Ford WT et al. Acute bacterial skin and skin structure infections (ABSSSI): practice guidelines for management and care transitions in the emergency department and hospital. J. Emerg. Med. 48(4), 508–519 (2015).
2.
Dryden MS. Complicated skin and soft tissue infection. J. Antimicrob. Chemother. 65(Suppl. 3), iii35–iii44 (2010).
3.
Chambers HF. Pharmacology and the treatment of complicated skin and skin-structure infections. N. Engl. J. Med. 370(23), 2238–2239 (2014).
4.
Stevens DL, Bisno AL, Chambers HF et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin. Infect. Dis. 41(10), 1373–1406 (2005).
5.
Gould IM, David MZ, Esposito S et al. New insights into methicillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance. Int. J. Antimicrob. Agents. 39(2), 96–104 (2012).
• Reviews recent literature on the rise in methicillin-resistant Staphylococcus aureus resistance to newer antibiotics.
6.
Holmberg SD, Solomon SL, Blake PA. Health and economic impacts of antimicrobial resistance. Rev. Infect. Dis. 9(6), 1065–1078 (1987).
7.
Boyce JM, Landry M, Deetz TR, DuPont HL. Epidemiologic studies of an outbreak of nosocomial methicillin-resistant Staphylococcus aureus infections. Infect. Control. 2(2), 110–116 (1981).
8.
Engemann JJ, Carmeli Y, Cosgrove SE et al. Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection. Clin. Infect. Dis. 36(5), 592–598 (2003).
• Highlights the treatment costs associated with methicillin-resistant Staphylococcus aureus compared with methicillin-susceptible Staphylococcus aureus.
9.
Rubinstein E, Keynan Y. Vancomycin revisited – 60 years later. Front. Public Heal. 2, 217 (2014).
10.
Dhand A, Sakoulas G. Reduced vancomycin susceptibility among clinical Staphylococcus aureus isolates (’the MIC Creep’): implications for therapy. F1000 Med. Rep. 4, 4 (2012).
11.
European Medicines Agency. Assessment report for ceftaroline fosamil. Procedure No.: EMEA/H/C/002252 (2012). www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002252/WC500132587.pdf
12.
Corey GR, Wilcox MH, Talbot GH, Thye D, Friedland D, Baculik T. CANVAS 1: the first Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J. Antimicrob. Chemother. 65(Suppl. 4), iv41–iv51 (2010).
13.
Wilcox MH, Corey GR, Talbot GH, Thye D, Friedland D, Baculik T. CANVAS 2: the second Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J. Antimicrob. Chemother. 65(Suppl. 4), iv53–iv65 (2010).
14.
Dryden M, Wilson D, Iaconis J, Gonzalez J. A Phase III trial of ceftaroline fosamil 600 mg q8h versus vancomycin plus aztreonam in patients with cSSTI with systemic inflammatory response or underlying comorbidities. In: European Congress of Clinical Microbiology and Infectious Diseases. Copenhagen, Denmark, 25–28 April 2015.
15.
Corey GR, Wilcox M, Talbot GH et al. Integrated analysis of CANVAS 1 and 2: Phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection. Clin. Infect. Dis. 51(6), 641–650 (2010).
16.
Santos PD, Davis A, Jandourek A, Smith A, David Friedland H. Ceftaroline fosamil and treatment of acute bacterial skin and skin structure infections: CAPTURE study experience. J. Chemother. 25(6), 341–346 (2013).
• This was the first study to demonstrate real-world efficacy of ceftaroline fosamil treatment of complicated skin and skin structure infections (cSSTIs).
17.
Guervil DJ, Kaye KS, Hassoun A, Cole P, Huang X-Y, Friedland HD. Ceftaroline fosamil as first-line versus second-line treatment for acute bacterial skin and skin structure infections (ABSSSI) or community-acquired bacterial pneumonia (CABP). J. Chemother. doi:1973947815Y0000000010 (2015) (Epub ahead of print).
18.
Charlson ME, Charlson RE, Peterson JC, Marinopoulos SS, Briggs WM, Hollenberg JP. The Charlson comorbidity index is adapted to predict costs of chronic disease in primary care patients. J. Clin. Epidemiol. 61(12), 1234–1240 (2008).
19.
Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm. Stat. 10(2), 150–161 (2011).
20.
Lee SY, Kuti JL, Nicolau DP. Antimicrobial management of complicated skin and skin structure infections in the era of emerging resistance. Surg. Infect. (Larchmt). 6(3), 283–295 (2005).
21.
Nathwani D, Moitra S, Dunbar J, Crosby G, Peterkin G, Davey P. Skin and soft tissue infections: development of a collaborative management plan between community and hospital care. Int. J. Clin. Pract. 52(7), 456–460 (1998).
22.
Maragakis LL, Perencevich EN, Cosgrove SE. Clinical and economic burden of antimicrobial resistance. Expert Rev. Anti. Infect. Ther. 6(5), 751–763 (2008).
23.
Marton JP, Jackel JL, Carson RT, Rothermel CD, Friedman M, Menzin J. Costs of skin and skin structure infections due to Staphylococcus aureus: an analysis of managed-care claims. Curr. Med. Res. Opin. 24(10), 2821–2828 (2008).
24.
Suaya Ja, Mera RM, Cassidy A et al. Incidence and cost of hospitalizations associated with Staphylococcus aureus skin and soft tissue infections in the United States from 2001 through 2009. BMC Infect. Dis. 14(1), 296 (2014).
25.
Muszbek N, Chapman R, Browne C et al. Using daptomycin in hospitalised patients with cSSTI caused by Staphylococcus aureus has an impact on costs. Chemotherapy 59(6), 427–434 (2013).
26.
Zervos MJ, Freeman K, Vo L et al. Epidemiology and outcomes of complicated skin and soft tissue infections in hospitalized patients. J. Clin. Microbiol. 50(2), 238–245 (2011).
27.
Garau J, Ostermann H, Medina J, Avila M, McBride K, Blasi F. Current management of patients hospitalized with complicated skin and soft tissue infections across Europe (2010–2011): assessment of clinical practice patterns and real-life effectiveness of antibiotics from the REACH study. Clin. Microbiol. Infect. 19(9), E377–E385 (2013).
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Ceftaroline fosamil treatment outcomes compared with standard of care among hospitalized patients with complicated skin and soft tissue infections. (2016) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2015-0024
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