Title
Ceftaroline fosamil for treatment of diabetic foot infections: The CAPTURE study experience
B. A. Lipsky1, C. M. Cannon2, A. Ramani3, A. Jandourek4, A. Calmaggi4, H. D. Friedland4, E. J. C. Goldstein5 1
University of Oxford, Oxford, UK; University of Geneva, Geneva, Switzerland; University of Washington, Seattle, USA 2 University of Kansas Hospital, Department of Emergency Medicine, Kansas City, Kansas, USA 3 Mountainview Medical Practice, Columbia Memorial Hospital, Hudson, NY 4 Cerexa Inc, Oakland, CA; USA 5 UCLA School of Medicine, Los Angeles, CA, and R M Alden Research Laboratory, Santa Monica, CA, USA
Corresponding author: Professor Benjamin A Lipsky, MD, FACP, FIDSA, FRCP Green Templeton College, University of Oxford 79 Stone Meadow, Oxford, UK OX2 6TD [email protected] Tel: 44 (0)1865 559078
Short title: Ceftaroline fosamil treatment of DFIs
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/dmrr.2624
This article is protected by copyright. All rights reserved.
Abstract Background. To ascertain which demographic, clinical and microbiological factors might affect clinical outcomes of patients with diabetic foot infections, excluding known osteomyelitis, by analysing CAPTURE registry study data of patients treated with ceftaroline fosamil. Methods. At participating study centres, we collected data by randomised selection and chart review, including patient demographics, co-morbidities, infecting pathogens, antibiotic use, surgical interventions and clinical response. Evaluable patients were those with data sufficient to determine clinical outcome. Clinical success was defined as clinical cure with no use of other antibiotics, or clinical improvement with a switch to oral antibiotic therapy at the end of intravenous ceftaroline fosamil treatment. Results. Among 201 patients (mean age 61.7 years, mean body mass index 33.2, 57% males), 40% had peripheral vascular disease (PVD). Prior antibiotic therapy had been given to 161 (80%) of the patients, most commonly with vancomycin and/or piperacillintazobactam. Patients received ceftaroline fosamil for a mean duration of 6.1 (range 1 – 30) days, as monotherapy in 130 (65%) patients and concurrently with other antibiotics in 71 (35%). Bacterial pathogens were identified in 114 (57%) of the patients; methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus were isolated from 56 (49%) and 28 (25%) of culture-positive patients, respectively. Clinical success was noted in 81% of patients and was not significantly associated with co-morbidities, pathogen type, or need for surgical intervention. Conclusions. Ceftaroline fosamil treatment of diabetic foot infections was associated with high clinical success, including in patients with obesity, co-morbidities, MRSA or mixed infections, or requiring surgical intervention.
Some of the results of this study have been previously reported in the form of an abstract (Lipsky BA, Calmaggi AC, Goldstein EJC. Ceftaroline fosamil for the treatment of diabetic foot infections: CAPTURE study experience [abstract] Diabetic Foot Global Conference, Los Angeles, 2014).
Keywords: diabetic foot infections, ceftaroline, CAPTURE, MRSA, skin or soft tissue infection, acute bacterial skin and soft tissue infection (ABSSSI), broad-spectrum antibiotic
This article is protected by copyright. All rights reserved.
Introduction Foot infections are a common and serious complication of diabetes associated with substantial morbidity and are an important proximate cause of amputations and occasionally mortality [1,2,3]. Moderate to severe diabetic foot infections (DFIs) are frequently polymicrobial, with aerobic Gram-positive cocci, especially staphylococci, as the most common causative organisms but Gram-negatives often involved as well [4,5]. In the past 15 years methicillin-resistant Staphylococcus aureus (MRSA) has become an increasingly common pathogen in DFIs [5,6,7]. Treatment of DFIs generally involves surgical intervention (e.g., debridement, incision and drainage) and always requires antimicrobial therapy. For severe infections, systemic antimicrobial therapy should be administered expeditiously, and is usually selected on an empirical basis [8,9]. While clinical trials have shown that many antibiotics are effective in treating DFIs, no specific antimicrobial agent or regimen has been shown to be superior to others [8,10,11,12]. The United States Food and Drug Administration (FDA) has approved many antibiotics for treating skin and soft tissue infections, but only three (ertapenem, linezolid and piperacillin-tazobactam) specifically for „complicated skin and skin structure infections including DFI‟, but not those associated with osteomyelitis [1]. Ertapenem and piperacillin-tazobactam have no antimicrobial activity against MRSA, while linezolid has activity only against Gram-positive pathogens. Ceftaroline, the active metabolite of ceftaroline fosamil (Teflaro®, Forest Laboratories), is a cephalosporin antibiotic with broad spectrum in vitro activity against Gram-positive and Gram-negative pathogens [13]. Unlike many β-lactams, ceftaroline also binds to penicillin binding protein 2a in MRSA, thereby achieving bactericidal activity against these otherwise resistant strains [14,15]. Ceftaroline demonstrates excellent in vitro activity against most of the aerobic pathogens typically found in moderate to severe DFI, including adequate coverage for MRSA and some Gram-negative pathogens [5]. The efficacy of ceftaroline fosamil in patients who were diagnosed with complicated skin and skin structure infections has been evaluated in two Phase III clinical studies, CANVAS 1 and CANVAS 2 [16,17]. However, in accordance with FDA guidance to industry at that time [18], patients with infected diabetic foot wounds were specifically excluded from these studies. The Clinical Assessment Program and Teflaro® Utilization Registry (CAPTURE) was designed to collect information on the routine clinical use of ceftaroline for all types of acute skin and skin structure infections (ABSSSIs), hereafter referred to as skin or soft tissue infections, including DFIs, in the US. Thus, the CAPTURE data allow us to present clinical information on the use of ceftaroline for the treatment of DFIs.
This article is protected by copyright. All rights reserved.
Materials and Methods Study design CAPTURE is a multicentre, retrospective cohort study of adult patients treated with intravenous ceftaroline fosamil for skin or soft tissue infections, including DFIs, but excluding cases associated with osteomyelitis. Each participating institution‟s institutional review or human subjects committee approved the study, which was conducted in compliance with the International Conference on Harmonisation E6 Good Clinical Practice guidance. The analyses in this study are based on data collected from August 2011 to August 2013. We identified medical charts from hospital wards, intensive care units (ICUs) and outpatient antibiotic therapy (OPAT) units through a combined review of pharmacy data and screening logs produced by the investigative site personnel to identify those patients with skin or soft tissue infections . For sites with fewer than 60% of their study population with skin or soft tissue infections , the data were collected for all the eligible patients. For sites that listed more than 60% of patients with skin or soft tissue infections , the contract research organisation randomised the order of charts on the pharmacy list. The sites proceeded sequentially through these randomly ordered lists to identify the patients whose charts were screened as well as the eligible patients whose charts were to undergo full review. To ensure retrospective collection of the data, patients had to have received their final dose of ceftaroline at least 30 days before the start of data collection. All patients received at least four consecutive doses of ceftaroline for skin or soft tissue infections. Study population Patients included in the current study were adults (≥ 18 years) with diabetes mellitus diagnosed with a skin or soft tissue infection of the foot, involving deeper soft tissue or requiring substantial surgical intervention. These included patients with a deep wound infection (post-surgical or traumatic), a major abscess, an infected ulceration, or deep and extensive cellulitis. We excluded patients with known osteomyelitis and those whose patient chart information on ceftaroline dosing or discharge disposition from the hospital was missing. Data Collection For each eligible patient we collected data relating to their demographics, medical and surgical histories, clinical signs and symptoms both at the time of diagnosis and at the end of ceftaroline treatment, and the causative skin or soft tissue pathogen(s). The information provided on specimens processed for culture described them as coming either from a skin or soft tissue source (potentially obtained at bedside, from a surgical procedure or needle aspirate) or blood culture. Other antimicrobial agents administered for skin or soft tissue infection before or during ceftaroline treatment were recorded, as were the location of care (intensive care unit, hospital ward, outpatient parenteral antibiotic therapy units) and the destination of the patient
This article is protected by copyright. All rights reserved.
following discharge from the hospital. Records were made of the reasons for discontinuation of ceftaroline, including those due to adverse events. Statistical Analyses Statistical analyses were performed on the data using SAS® Version 9.2 (SAS Institute Inc., Cary, NC, USA). The data were summarised using primarily descriptive statistics, based on the evaluable population, i.e., patients whose records provided data sufficient to determine a clinical outcome of success or failure. The enrolled population included each patient who met all inclusion and no exclusion criteria. The evaluable population included each patient who met all eligibility criteria and had a clinical outcome of clinical success or clinical failure, based upon investigator judgment and whether or not they were treated with other antibiotics for the infection. No specific criteria were otherwise applied to assess the efficacy of ceftaroline fosamil in patients who underwent surgical procedures, including amputation. Clinical success was defined as one of the following: (a) clinical cure, as determined by the investigator, with no further use of other antibiotics to treat the infection; (b) clinical improvement, as defined by a switch to oral antibiotic, or investigator review of available clinical information (including queries that had been recorded) confirming that a patient was improving on treatment, without evidence of clinical failure, at the time of ceftaroline discontinuation. Clinical outcome was analysed according to: 1) whether ceftaroline was used as monotherapy or as concurrent therapy; 2) whether ceftaroline was used as first-line therapy (i.e., no recent prior antibiotic treatment) or as second-line therapy (after another agent was used); and, 3) by isolated bacterial pathogens. Clinical outcome was also analysed for subsets of patients with what we considered a priori to be key co-morbidities and were consistently collected in this study, i.e., patients who were obese (body mass index [BMI] ≥ 30), who had peripheral vascular disease (PVD), or who had severe infections secondary to trauma with a requirement for surgical intervention.
This article is protected by copyright. All rights reserved.
Results Patient population We enrolled a total of 1,392 clinically evaluable patients diagnosed with skin or soft tissue infections from 46 sites into the CAPTURE study between August 2011 and August 2013. Of these, 201 (14.4%) had diabetes mellitus and were diagnosed with a foot infection (DFI population). The mean age of the DFI population was 61.7 years (SD ± 13.7, range 25–93 years), 115 patients (57.2%) were male and 81 (40.3%) had PVD (Table 1). The mean BMI was 33.2 (SD ± 8.4) and the majority of patients (160/201) were overweight (25.9%) or obese (54.0%). Most (90.0%) of the DFI patients were treated in a general hospital ward during ceftaroline administration; 19 patients were treated in an intensive care unit and one received outpatient parenteral antibiotic therapy. Baseline serum creatinine levels, collected starting in August 2012 of the study, were available for 85 (42.3%) of the 201 DFI subjects; 21 (24.7%) of these had low renal clearance (a serum creatinine of >1.8 mg/dL). Antibiotic therapy Of the 201 evaluable patients in the DFI population, the majority (80.1%) had received other recent antibiotic therapy prior to treatment with ceftaroline; however, the duration of this therapy was not recorded on our data forms. The most common of the previously used agents (see Table 2) included glycopeptides (45%), penicillins (34%), quinolones (14%), cephalosporins (33%), lincosamides (10%) and sulfonamides (5%). Almost all patients (97%) received ceftaroline on a dosing regimen of 600 mg every 12 hours. Patients received ceftaroline for a mean of 6.1 (range 1–30) days; in 130 (64.6%) it was given as monotherapy and in 71 (35.3%) concurrently with one or more other antibiotic agents, including glycopeptides (9%), penicillins (6%), fluoroquinolones (6%) and lincosamides (8%). Microbiology Bacterial pathogens were recovered from 114 (56.7%) of the DFI patients; these were collected from skin, soft tissue or wound cultures in 104 (51.7%), and from blood cultures in 10 (5.0%). S. aureus, either alone or as part of a polymicrobial infection, was recovered from 83 patients (see Table 3). MRSA and methicillin-sensitive S. aureus (MSSA) were isolated as single pathogens from 33 patients and 16 patients, respectively, and as part of a polymicrobial infection from a further 23 and 11 patients, respectively. Infections caused by bacterial pathogens other than S. aureus were recovered from 31 patients. These included isolates of Acinetobacter sp., Bacteroides sp., coagulase-negative staphylococci, corynebacteria, diphtheroids, Escherichia coli, Enterobacter sp. Eikenella sp., Enterococcus faecalis, Klebsiella pneumoniae, Morganella morganii, Pantoea sp., Peptostreptococcus sp., Providencia sp. Pseudomonas spp., Streptococcus agalactiae, S. anginosus/miller, S. viridans, Serratia marcescens, and Stenotrophomonas spp. The number of patients with a gram-negative isolate was small and the vast majority were co-pathogens with a grampositive organism. The most commonly identified were Proteus mirabilis (7 patients),
This article is protected by copyright. All rights reserved.
Klebsiella pneumoniae (5 patients), Pseudomonas aeruginosa (5 patients), and Escherichia coli (5 patients). Susceptibility of isolates to ceftaroline was rarely determined because commercial testing kits for ceftaroline were initially not available and when they were during the latter part of the study period they were used at only a limited number of sites. Severity of wounds Deep or extensive cellulitis was the most common infection type (111 patients, 55.2%), followed by infected ulcers (67, 33.3%) and abscesses (21, 10.5%). A total of 25 (12.4%) patients had infected surgical or traumatic wounds. At least one surgical procedure was required for 94 (46.8%) of the patients (see Table 3). The majority (60/94 [63.8%]) of surgical patients underwent a single surgical procedure, generally amputation (26 patients), debridement (18 patients) or incision and drainage (12 patients). Two surgical procedures were performed on 30 patients and four patients underwent three surgical procedures. Clinical outcome Overall, treatment with ceftaroline was associated with clinical success in 163 of the 201 patients (81.1%) in the DFI population (see Table 3). Clinical success rates were not significantly different in those without PVD (85.8%) compared with those with PVD (74.1%), or among obese patients (88.9%) compared with those in other BMI categories. Similarly, there was no significant difference in clinical success rates in the 21 patients with low renal clearance versus the 64 patients with normal (serum creatinine
Ceftaroline fosamil for treatment of diabetic foot infections: The CAPTURE study experience
B. A. Lipsky1, C. M. Cannon2, A. Ramani3, A. Jandourek4, A. Calmaggi4, H. D. Friedland4, E. J. C. Goldstein5 1
University of Oxford, Oxford, UK; University of Geneva, Geneva, Switzerland; University of Washington, Seattle, USA 2 University of Kansas Hospital, Department of Emergency Medicine, Kansas City, Kansas, USA 3 Mountainview Medical Practice, Columbia Memorial Hospital, Hudson, NY 4 Cerexa Inc, Oakland, CA; USA 5 UCLA School of Medicine, Los Angeles, CA, and R M Alden Research Laboratory, Santa Monica, CA, USA
Corresponding author: Professor Benjamin A Lipsky, MD, FACP, FIDSA, FRCP Green Templeton College, University of Oxford 79 Stone Meadow, Oxford, UK OX2 6TD [email protected] Tel: 44 (0)1865 559078
Short title: Ceftaroline fosamil treatment of DFIs
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/dmrr.2624
This article is protected by copyright. All rights reserved.
Abstract Background. To ascertain which demographic, clinical and microbiological factors might affect clinical outcomes of patients with diabetic foot infections, excluding known osteomyelitis, by analysing CAPTURE registry study data of patients treated with ceftaroline fosamil. Methods. At participating study centres, we collected data by randomised selection and chart review, including patient demographics, co-morbidities, infecting pathogens, antibiotic use, surgical interventions and clinical response. Evaluable patients were those with data sufficient to determine clinical outcome. Clinical success was defined as clinical cure with no use of other antibiotics, or clinical improvement with a switch to oral antibiotic therapy at the end of intravenous ceftaroline fosamil treatment. Results. Among 201 patients (mean age 61.7 years, mean body mass index 33.2, 57% males), 40% had peripheral vascular disease (PVD). Prior antibiotic therapy had been given to 161 (80%) of the patients, most commonly with vancomycin and/or piperacillintazobactam. Patients received ceftaroline fosamil for a mean duration of 6.1 (range 1 – 30) days, as monotherapy in 130 (65%) patients and concurrently with other antibiotics in 71 (35%). Bacterial pathogens were identified in 114 (57%) of the patients; methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus were isolated from 56 (49%) and 28 (25%) of culture-positive patients, respectively. Clinical success was noted in 81% of patients and was not significantly associated with co-morbidities, pathogen type, or need for surgical intervention. Conclusions. Ceftaroline fosamil treatment of diabetic foot infections was associated with high clinical success, including in patients with obesity, co-morbidities, MRSA or mixed infections, or requiring surgical intervention.
Some of the results of this study have been previously reported in the form of an abstract (Lipsky BA, Calmaggi AC, Goldstein EJC. Ceftaroline fosamil for the treatment of diabetic foot infections: CAPTURE study experience [abstract] Diabetic Foot Global Conference, Los Angeles, 2014).
Keywords: diabetic foot infections, ceftaroline, CAPTURE, MRSA, skin or soft tissue infection, acute bacterial skin and soft tissue infection (ABSSSI), broad-spectrum antibiotic
This article is protected by copyright. All rights reserved.
Introduction Foot infections are a common and serious complication of diabetes associated with substantial morbidity and are an important proximate cause of amputations and occasionally mortality [1,2,3]. Moderate to severe diabetic foot infections (DFIs) are frequently polymicrobial, with aerobic Gram-positive cocci, especially staphylococci, as the most common causative organisms but Gram-negatives often involved as well [4,5]. In the past 15 years methicillin-resistant Staphylococcus aureus (MRSA) has become an increasingly common pathogen in DFIs [5,6,7]. Treatment of DFIs generally involves surgical intervention (e.g., debridement, incision and drainage) and always requires antimicrobial therapy. For severe infections, systemic antimicrobial therapy should be administered expeditiously, and is usually selected on an empirical basis [8,9]. While clinical trials have shown that many antibiotics are effective in treating DFIs, no specific antimicrobial agent or regimen has been shown to be superior to others [8,10,11,12]. The United States Food and Drug Administration (FDA) has approved many antibiotics for treating skin and soft tissue infections, but only three (ertapenem, linezolid and piperacillin-tazobactam) specifically for „complicated skin and skin structure infections including DFI‟, but not those associated with osteomyelitis [1]. Ertapenem and piperacillin-tazobactam have no antimicrobial activity against MRSA, while linezolid has activity only against Gram-positive pathogens. Ceftaroline, the active metabolite of ceftaroline fosamil (Teflaro®, Forest Laboratories), is a cephalosporin antibiotic with broad spectrum in vitro activity against Gram-positive and Gram-negative pathogens [13]. Unlike many β-lactams, ceftaroline also binds to penicillin binding protein 2a in MRSA, thereby achieving bactericidal activity against these otherwise resistant strains [14,15]. Ceftaroline demonstrates excellent in vitro activity against most of the aerobic pathogens typically found in moderate to severe DFI, including adequate coverage for MRSA and some Gram-negative pathogens [5]. The efficacy of ceftaroline fosamil in patients who were diagnosed with complicated skin and skin structure infections has been evaluated in two Phase III clinical studies, CANVAS 1 and CANVAS 2 [16,17]. However, in accordance with FDA guidance to industry at that time [18], patients with infected diabetic foot wounds were specifically excluded from these studies. The Clinical Assessment Program and Teflaro® Utilization Registry (CAPTURE) was designed to collect information on the routine clinical use of ceftaroline for all types of acute skin and skin structure infections (ABSSSIs), hereafter referred to as skin or soft tissue infections, including DFIs, in the US. Thus, the CAPTURE data allow us to present clinical information on the use of ceftaroline for the treatment of DFIs.
This article is protected by copyright. All rights reserved.
Materials and Methods Study design CAPTURE is a multicentre, retrospective cohort study of adult patients treated with intravenous ceftaroline fosamil for skin or soft tissue infections, including DFIs, but excluding cases associated with osteomyelitis. Each participating institution‟s institutional review or human subjects committee approved the study, which was conducted in compliance with the International Conference on Harmonisation E6 Good Clinical Practice guidance. The analyses in this study are based on data collected from August 2011 to August 2013. We identified medical charts from hospital wards, intensive care units (ICUs) and outpatient antibiotic therapy (OPAT) units through a combined review of pharmacy data and screening logs produced by the investigative site personnel to identify those patients with skin or soft tissue infections . For sites with fewer than 60% of their study population with skin or soft tissue infections , the data were collected for all the eligible patients. For sites that listed more than 60% of patients with skin or soft tissue infections , the contract research organisation randomised the order of charts on the pharmacy list. The sites proceeded sequentially through these randomly ordered lists to identify the patients whose charts were screened as well as the eligible patients whose charts were to undergo full review. To ensure retrospective collection of the data, patients had to have received their final dose of ceftaroline at least 30 days before the start of data collection. All patients received at least four consecutive doses of ceftaroline for skin or soft tissue infections. Study population Patients included in the current study were adults (≥ 18 years) with diabetes mellitus diagnosed with a skin or soft tissue infection of the foot, involving deeper soft tissue or requiring substantial surgical intervention. These included patients with a deep wound infection (post-surgical or traumatic), a major abscess, an infected ulceration, or deep and extensive cellulitis. We excluded patients with known osteomyelitis and those whose patient chart information on ceftaroline dosing or discharge disposition from the hospital was missing. Data Collection For each eligible patient we collected data relating to their demographics, medical and surgical histories, clinical signs and symptoms both at the time of diagnosis and at the end of ceftaroline treatment, and the causative skin or soft tissue pathogen(s). The information provided on specimens processed for culture described them as coming either from a skin or soft tissue source (potentially obtained at bedside, from a surgical procedure or needle aspirate) or blood culture. Other antimicrobial agents administered for skin or soft tissue infection before or during ceftaroline treatment were recorded, as were the location of care (intensive care unit, hospital ward, outpatient parenteral antibiotic therapy units) and the destination of the patient
This article is protected by copyright. All rights reserved.
following discharge from the hospital. Records were made of the reasons for discontinuation of ceftaroline, including those due to adverse events. Statistical Analyses Statistical analyses were performed on the data using SAS® Version 9.2 (SAS Institute Inc., Cary, NC, USA). The data were summarised using primarily descriptive statistics, based on the evaluable population, i.e., patients whose records provided data sufficient to determine a clinical outcome of success or failure. The enrolled population included each patient who met all inclusion and no exclusion criteria. The evaluable population included each patient who met all eligibility criteria and had a clinical outcome of clinical success or clinical failure, based upon investigator judgment and whether or not they were treated with other antibiotics for the infection. No specific criteria were otherwise applied to assess the efficacy of ceftaroline fosamil in patients who underwent surgical procedures, including amputation. Clinical success was defined as one of the following: (a) clinical cure, as determined by the investigator, with no further use of other antibiotics to treat the infection; (b) clinical improvement, as defined by a switch to oral antibiotic, or investigator review of available clinical information (including queries that had been recorded) confirming that a patient was improving on treatment, without evidence of clinical failure, at the time of ceftaroline discontinuation. Clinical outcome was analysed according to: 1) whether ceftaroline was used as monotherapy or as concurrent therapy; 2) whether ceftaroline was used as first-line therapy (i.e., no recent prior antibiotic treatment) or as second-line therapy (after another agent was used); and, 3) by isolated bacterial pathogens. Clinical outcome was also analysed for subsets of patients with what we considered a priori to be key co-morbidities and were consistently collected in this study, i.e., patients who were obese (body mass index [BMI] ≥ 30), who had peripheral vascular disease (PVD), or who had severe infections secondary to trauma with a requirement for surgical intervention.
This article is protected by copyright. All rights reserved.
Results Patient population We enrolled a total of 1,392 clinically evaluable patients diagnosed with skin or soft tissue infections from 46 sites into the CAPTURE study between August 2011 and August 2013. Of these, 201 (14.4%) had diabetes mellitus and were diagnosed with a foot infection (DFI population). The mean age of the DFI population was 61.7 years (SD ± 13.7, range 25–93 years), 115 patients (57.2%) were male and 81 (40.3%) had PVD (Table 1). The mean BMI was 33.2 (SD ± 8.4) and the majority of patients (160/201) were overweight (25.9%) or obese (54.0%). Most (90.0%) of the DFI patients were treated in a general hospital ward during ceftaroline administration; 19 patients were treated in an intensive care unit and one received outpatient parenteral antibiotic therapy. Baseline serum creatinine levels, collected starting in August 2012 of the study, were available for 85 (42.3%) of the 201 DFI subjects; 21 (24.7%) of these had low renal clearance (a serum creatinine of >1.8 mg/dL). Antibiotic therapy Of the 201 evaluable patients in the DFI population, the majority (80.1%) had received other recent antibiotic therapy prior to treatment with ceftaroline; however, the duration of this therapy was not recorded on our data forms. The most common of the previously used agents (see Table 2) included glycopeptides (45%), penicillins (34%), quinolones (14%), cephalosporins (33%), lincosamides (10%) and sulfonamides (5%). Almost all patients (97%) received ceftaroline on a dosing regimen of 600 mg every 12 hours. Patients received ceftaroline for a mean of 6.1 (range 1–30) days; in 130 (64.6%) it was given as monotherapy and in 71 (35.3%) concurrently with one or more other antibiotic agents, including glycopeptides (9%), penicillins (6%), fluoroquinolones (6%) and lincosamides (8%). Microbiology Bacterial pathogens were recovered from 114 (56.7%) of the DFI patients; these were collected from skin, soft tissue or wound cultures in 104 (51.7%), and from blood cultures in 10 (5.0%). S. aureus, either alone or as part of a polymicrobial infection, was recovered from 83 patients (see Table 3). MRSA and methicillin-sensitive S. aureus (MSSA) were isolated as single pathogens from 33 patients and 16 patients, respectively, and as part of a polymicrobial infection from a further 23 and 11 patients, respectively. Infections caused by bacterial pathogens other than S. aureus were recovered from 31 patients. These included isolates of Acinetobacter sp., Bacteroides sp., coagulase-negative staphylococci, corynebacteria, diphtheroids, Escherichia coli, Enterobacter sp. Eikenella sp., Enterococcus faecalis, Klebsiella pneumoniae, Morganella morganii, Pantoea sp., Peptostreptococcus sp., Providencia sp. Pseudomonas spp., Streptococcus agalactiae, S. anginosus/miller, S. viridans, Serratia marcescens, and Stenotrophomonas spp. The number of patients with a gram-negative isolate was small and the vast majority were co-pathogens with a grampositive organism. The most commonly identified were Proteus mirabilis (7 patients),
This article is protected by copyright. All rights reserved.
Klebsiella pneumoniae (5 patients), Pseudomonas aeruginosa (5 patients), and Escherichia coli (5 patients). Susceptibility of isolates to ceftaroline was rarely determined because commercial testing kits for ceftaroline were initially not available and when they were during the latter part of the study period they were used at only a limited number of sites. Severity of wounds Deep or extensive cellulitis was the most common infection type (111 patients, 55.2%), followed by infected ulcers (67, 33.3%) and abscesses (21, 10.5%). A total of 25 (12.4%) patients had infected surgical or traumatic wounds. At least one surgical procedure was required for 94 (46.8%) of the patients (see Table 3). The majority (60/94 [63.8%]) of surgical patients underwent a single surgical procedure, generally amputation (26 patients), debridement (18 patients) or incision and drainage (12 patients). Two surgical procedures were performed on 30 patients and four patients underwent three surgical procedures. Clinical outcome Overall, treatment with ceftaroline was associated with clinical success in 163 of the 201 patients (81.1%) in the DFI population (see Table 3). Clinical success rates were not significantly different in those without PVD (85.8%) compared with those with PVD (74.1%), or among obese patients (88.9%) compared with those in other BMI categories. Similarly, there was no significant difference in clinical success rates in the 21 patients with low renal clearance versus the 64 patients with normal (serum creatinine
