1817 Ceftaroline Fosamil for the Treatment of Hospital-acquired Pneumonia (HAP) and ID WEEK 2015 San Diego, CA Ventilator-associated Pneumonia (VAP): CAPTURE Study Experience David J Guervil, PharmD Memorial Hermann-Texas Medical Center, 1 2 3 4 1 2 3 4 7–11 October G Udeani, DJ Guervil, LB Johnson, KS Kaye Corpus Christi Medical Center, Corpus Christi, TX; Memorial Hermann-Texas Medical Center, Houston, TX; St. John Hospital and Medical Center, Detroit, MI; Detroit Medical Center and Wayne State University, Detroit, MI Houston, TX | [email protected] Clinical success Abstract Materials and Methods Table 1. Relevant medical history (N = 44 ) Table 2. Patients with pathogens isolated (N = 44) Clinical success was 77% overall: 83% in patients with HAP and 64% in patients with VAP (Figure 2) Background. Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are serious infections increasingly Data were collected for patients at participating centers in the US by random ordering and sequential review of patient charts Pathogen Number of patients, n (%) Condition Number of patients, n (%) Success rates of 74% and 80% were seen in patients with a history of smoking and structural lung disease associated with resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). CAPTURE is a multicenter registry between September 2013 and February 2015 Any pathogen 28 (63.6) study describing patients (pts) treated with ceftaroline fosamil (CPT-F) in the US. Clinical study experience for the use of CPT-F in treatment Smoking 23 (52.3) Among patients who had any pathogen isolated, clinical success rate was 64% (18/28), and was 62% (13/21) among patients with of pts with HAP/VAP, defined according to ATS/IDSA guidelines, is presented. Inclusion criteria included MRSA MRSA isolated; the one patient with MSSA was also a clinical success Structural lung disease 21 (47.7) Methods. Data were collected from participating sites by randomly ordered chart review between Sep 2013 and Feb 2015, which included • male or female, ≥ 18 years of age 20 (45.5) Figure 3 demographics, disease characteristics, antibiotic use, location of care, pathogens isolated, and clinical response. Evaluable pts were those 1 Escherichia coli 3 (6.8) Clinical success rates by antibiotic therapy and location of care are shown in • final diagnosis of HAP or VAP according to ATS/IDSA criteria Gastroesophageal reflux with a clinical outcome determined. Clinical success was defined as clinical cure or clinical improvement. 11 (25.0) • success rate among patients in the general hospital ward was 100%, and for patients in the ICU, 67% • patient had received ≥ 4 consecutive intravenous (IV) doses of ceftaroline fosamil Pseudomonas aeruginosa 2 (4.5) Results. In the evaluable population 44/1274 (3%) had HAP/VAP, 30 had HAP and 14 had VAP. Demographics: 57% male; mean age 60.5 • in patients who had received prior antibiotic therapy, the success rate was 82% Prior pneumonia 10 (22.7) years (SD ± 17.4, range 18–91); and 43% required mechanical ventilation. The most commonly reported comorbidities were smoking, Exclusion criteria included Klebsiella oxytoca 2 (4.5) • in patients who received ceftaroline fosamil as monotherapy, the success rate was 83% 52%; structural lung disease, 45%; and gastroesophageal reflux (GERD), 25%. Antibiotics were administered prior to CPT-F in 86%, most • missing data: information on the patient’s ceftaroline fosamil dosing or hospital admission or discharge Congestive heart failure 8 (18.2) commonly vancomycin, 68%; piperacillin-tazobactam, 43%; and levofloxacin, 20%. Concurrent antibiotics were administered in 45% of Morganella morganii 1 (2.3) • the success rate was 70% in patients who received concurrent antibiotic treatment pts; most commonly vancomycin, 14%. Most pts were treated in the ICU, 68%. The overall mean (± SD) duration of CPT-F therapy was 6.9 • charts from which data were previously extracted for this study Alcoholism 7 (15.9) ± 3.4 days; 6.8 ± 3.3 days for ICU pts; and 7.2 ± 3.6 days for general hospital ward pts. Ten pts, 23%, all treated in ICU, had associated Haemophilus influenzae Data collection included 1 (2.3) bacteremia. Pathogens were isolated from 64% of pts; most commonly MRSA, 48% and Escherichia coli, 7%. Clinical success rates are Figure 2. Clinical success by diagnosis and by comorbidities Stroke 4 (9.1) MSSA shown in the table. • patient demographics, relevant medical history, disease characteristics 1 (2.3) • location of care and supplemental oxygen use Hemodialysis 100 Conclusions. Clinical success with CPT-F was favorable in pts with HAP/VAP, particularly considering comorbidities, high level of acuity 2 (4.5) Other pathogens 1 (2.3) and ventilator dependence; and the fact that most received CPT-F as 2nd-line therapy. • previous, concurrent, and subsequent use of antibiotics MRSA, methicillin-resistant Staphylococcus aureus; 80 Clinical success rates n/N (%) • duration of ceftaroline fosamil use MSSA, methicillin-susceptible Staphylococcus aureus • clinical response Overall 34/44 (77) 60 Antibiotic use ICU 20/30 (67) The evaluable population consisted of enrolled patients who had available information on clinical response to determine a clinical GHW 14/14 (100) outcome (clinical success or clinical failure) 40 Before starting treatment with ceftaroline fosamil, 38 (86%) patients had received prior antibiotic treatment, most frequently of patients % ≥ 1 comorbidity 33/43 (77) Clinical success was defined as: • vancomycin (30 patients [68%]) Smoking 20 17/23 (74) • clinical cure with no further need for antibiotics, or • piperacillin/tazobactam (19 patients [43%]) Structural lung disease 16/20 (80) • clinical improvement with switch to oral antibiotic treatment, or • levofloxacin (9 patients [20%]) 34/44 25/30 9/14 33/43 17/23 16/20 8/11 12/19 0 GERD 8/11 (73) • in some cases, review of information that the patient was improving on treatment without evidence of failure or discontinuation • cefepime (7 patients [16%]) Monotherapy 20/24 (83) 2nd-line therapy 31/38 (82) The mean duration of ceftaroline fosamil therapy was 6.9 ± 3.4 days; range, 3–17 days Pathogen isolated 18/28 (64) Results Most patients (93%) received ceftaroline fosamil every 12 h MRSA 13/21 (62) Ceftaroline fosamil was administered as monotherapy in 24 (55%) patients Figure 3. Clinical success by location of care and antibiotic usage Introduction Data records for 1274 patients were collected from participating centers • 20 (45%) patients received concurrent antibiotic treatment 17 centers contributed a total of 44 (3%) patient charts to either the HAP (n = 30) or the VAP (n = 14) data sets 19 (43%) patients continued treatment with other antibiotics after completion of ceftaroline fosamil 100 • 6 (14%) received vancomycin Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection in the US and is associated with high mortality Patient and baseline characteristics • no other individual subsequent antibiotic was given to more than three patients 80 and morbidity. It occurs at a rate of 5–10 per 1000 hospital admissions and the rate is increased 6–20-fold in mechanically ventilated Mean age was 60.5 ± 17.4 years; 17 (39%) patients were ≥ 65 years in age and 25 (57%) patients were male 1 patients. Ventilator-associated pneumonia (VAP) occurs in 9%–27% of all intubated patients 60 14 (32%) patients were in the general hospital ward during ceftaroline fosamil treatment, and 30 (68%) were in ICU Figure 1. Clinical signs and symptoms of HAP/VAP HAP and its sub-type VAP are associated with resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA) 33 (75%) patients were receiving supplemental oxygen: 9 (64%) in the general hospital ward and 24 (80%) in ICU 40 of patients % Ceftaroline fosamil is a cephalosporin antibiotic approved by the FDA for the treatment of community-acquired bacterial pneumonia 100 19 (43%) patients required support with mechanical ventilation: 2 (14%) in the general hospital ward and 17 (57%) in ICU █ Day of diagnosis █ End of treatment █ Day of diagnosis █ End of treatment and acute bacterial skin and skin structure infections. It has been approved for similar indications in the EU 20 Patients’ relevant medical history are summarized in Table 1 Ceftaroline has broad-spectrum in vitro activity against 80 14/14 20/30 3/6 31/38 20/24 14/20 0 • 98% of patients had at least one comorbidity • Gram-positive bacteria such as S. aureus and Streptococcus pneumoniae, including their resistant phenotypes (e.g., MRSA and General ICU First-line Second-line Monotherapy Concurrent • the most commonly reported comorbidities were smoking (52%) and structural lung disease (45%) multidrug-resistant S. pneumoniae [MDRSP]) hospital ward therapy therapy therapy 60 • Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Haemophilus influenzae. Ceftaroline, like other Disease characteristics cephalosporins, is not active against producers of extended-spectrum β-lactamases of patients % At the time of diagnosis, 84% of patients had two or more clinical signs and symptoms 40 • Ceftaroline targets the bacterial penicillin-binding proteins (PBPs) to inhibit synthesis of the bacterial cell wall, producing Overall, the most common signs and symptoms were bactericidal activity Conclusion 20 » PBP2a in MRSA – unlike other β-lactams approved in the US • at the time of diagnosis: abnormal auscultatory findings, in 36 (82%) patients; dyspnea, in 29 (66%); and sputum production, Clinical success rates were favorable when ceftaroline fosamil was used in the treatment of patients in 22 (50%) » PBP2x in MDRSP 11 6 11 6 10 5 8 4 3 1 0 0 19 12 9 8 25 13 14 13 7 1 4 4 with HAP/VAP in general hospital wards or ICUs • at the end of treatment: abnormal auscultatory findings, in 19 (43%) patients; dyspnea, in 17 (39%); and sputum production, 0 » These favorable outcomes were seen despite patients with significant comorbidities, high levels PBPs 1a and 3 in E.