Respiratory syncytial virus hospitalization trends in infants with chronic lung disease of infancy, 1998-2008.

OBJECTIVE: Infants with chronic lung disease of infancy (CLDI) are at high risk for severe respiratory syncytial virus (RSV) illness requiring hospitalization. Palivizumab was first licensed in 1998 for the prevention of RSV disease in high-risk infants, including those with CLDI. We performed a retrospective cohort study of all hospitalized children with CLDI aged <2 years between 1998 and 2008 in the USA to determine trends in rates of hospitalizations due to RSV (RSVH) since the launch of palivizumab. MATERIALS AND METHODS: Data from the United States National Hospital Discharge Survey, a multistage systematic survey sample of US hospitals, were assembled. We defined RSVH using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes of 079.6 (RSV), 466.11 (acute bronchiolitis due to RSV), and 480.1 (pneumonia due to RSV). Quarterly rates of RSVH were assessed for children with CLDI (ICD-9-CM code 770.7) and calculated between 1998 and 2008. Because RSV may be miscoded, the analysis was repeated after expanding the definition of RSVH to include all acute bronchitis and acute bronchiolitis (ABH) (ICD-9-CM = 466). Trends were described using linear regression with seasonal indicators included in the model. RESULTS: On average, about 966 RSVH (range 98-1373 RSVH) per year were found for children <2 years with CLDI in the USA between 1998 and 2008. Over the 11-year period, the predicted rate of RSVH statistically significantly decreased by 48% (from 93.78 to 49.06 RSVH per 1 million children) (P = 0.013). Addition of ABH resulted in a nonstatisically significant decrease of 32% over the 10-year period (P = 0.102). CONCLUSION: These results suggest that there has been a decrease in the rate of RSVH in infants with CLDI between 1998 and 2008. The reasons for this decrease may include improved neonatal intensive care unit and outpatient management of CLDI, and possibly increased use of palivizumab in this high-risk population.

Trends in chronologic age and infant respiratory syncytial virus hospitalization: an 8-year cohort study.

INTRODUCTION: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and young children and the leading cause of hospitalization in infants aged <1 year. METHODS: We examined trends in RSV hospitalization (RSVH) among infants from 1998 to 2006, using the United States (US) National Hospital Discharge Survey (NHDS) database. RSVH was defined by the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 079.6 (RSV), 466.11 (acute bronchiolitis due to RSV), and 480.1 (pneumonia due to RSV). Age at the time of hospitalization was determined using NHDS birth records; RSVH rates were analyzed for infants grouped into three age cohorts (<3 months, 3 to 6 months, and >6 to <24 months). Trends in hospitalization rates were evaluated using linear regression. Relative rates (RR) and 95% confidence intervals (CI) were computed to compare average RSVH rates for infants across age-specific groups. The annual proportion of RSVH by age group was also calculated. RESULTS: Approximately 1.1 million (90,000-147,000 per year) RSVHs in predominantly term children aged <24 months were analyzed. Compared with children aged >6 to <24 months, rates for RSVH were significantly higher among infants aged <3 months (RR, 7.38; 95% CI, 7.35-7.41) and infants aged 3 to 6 months (RR, 5.28; 95% CI, 5.26-5.29). The proportion of RSVH in the first year of life was lowest among infants aged <1 month (9%). [corrected] The greatest proportion of RSVH was observed in children aged 3 to 6 months (14%-23% RSVH per year; chi-square P<0.0001). When the definition of RSVH was expanded to include unspecified hospitalizations for acute bronchiolitis, similar results were observed. CONCLUSION: RRs were highest among the <3- month and 3- to 6-month age groups. The highest proportion of RSVH was among the 3- to 6-month age group. Analysis of the impact of RSV season, clinical practices, and other factors on these trends is warranted.

Prospective, non-comparative study of daptomycin for the treatment of superficial and deep incisional surgical site infections.

BACKGROUND: Skin infections, including surgical site infections (SSIs), usually involve gram-positive pathogens and continue to be a leading cause of morbidity and death among hospital patients. The increasing prevalence of methicillin-resistant Staphylococcus aureus and other resistant strains accentuates the need for effective and safe therapies for such infections. This exploratory study evaluated the efficacy and safety of daptomycin in patients with gram-positive SSI according to wound classification. METHODS: Eligible patients had an SSI with onset < 30 days after surgery, positive gram stain or culture at least three days before daptomycin therapy began, and three or more clinical signs and symptoms of infection. The incisional SSI was classified as superficial or deep according to the U.S. Centers for Disease Control and Prevention criteria. Patients with organ-space infections were excluded, as were those with major concomitant infections, foreign material in the incision that could not be removed, previous systemic antimicrobial therapy, or creatinine clearance < 30 mL/min. Daptomycin 4 mg/kg was administered intravenously once daily for 7-14 days. The primary efficacy endpoint was clinical response at the end of daptomycin therapy, and the safety assessment was based on adverse events (AEs). RESULTS: Sixty-nine patients were enrolled, 60 of whom were evaluable for efficacy. Extremity wounds predominated among superficial incisional SSIs (n = 30), whereas abdominal wounds predominated among deep SSIs (n = 30). Patients with deep incisional SSI were more likely to be young, male, white, and febrile and to weigh more than patients with superficial SSIs. The overall clinical success rate was 92% (95% confidence interval [CI] 82-97%); the success rate was 100% in superficial incisional SSI and 83% in deep SSI (17% difference; 95% CI 0-33%). Staphylococcus aureus (28/36 methicillin-resistant) was the pathogen isolated most frequently. In 10 patients who were febrile at baseline, the median time to defervescence was five days, and the mean duration of treatment in the series was 11.2 days. Daptomycin was well tolerated. In most patients, AEs were mild or moderate in intensity; in two patients (one superficial, one deep), daptomycin was discontinued because of AEs. CONCLUSIONS: The results of this exploratory study of SSI are consistent with those of previous studies of daptomycin in the treatment of diverse complicated skin and skin-structure infections, and suggest that wound classification should be treated as an important covariate in future studies of daptomycin and other antibiotics.

Interaction of daptomycin with two recombinant thromboplastin reagents leads to falsely prolonged patient prothrombin time/International Normalized Ratio results.

A cluster of patients experiencing elevations of International Normalized Ratio without clinical bleeding in temporal association with daptomycin therapy was identified during postmarketing safety surveillance. A common element was the thromboplastin reagent used for the laboratory assay. The present study evaluated the effect of daptomycin on measured prothrombin time using commercially available thromboplastin reagent kits commonly used in the United States. Thirty reagent kits were obtained. Daptomycin was added to pooled normal human plasma samples to achieve final concentrations of 0-200 microg/ml. Quality control ranges were established for each reagent kit using normal and abnormal control plasmas. Triplicate assays of the prothrombin time were performed on the daptomycin-spiked plasma samples using each of the 30 kits. The activated partial thromboplastin time and thrombin time were also assessed. Statistical comparisons of interest were performed using analysis of variance with the Bonferroni t-test for multiple comparisons; alpha = 0.05 was used. Addition of daptomycin to human plasma samples dose-dependently prolonged measured prothrombin times when two recombinant thromboplastin reagents were utilized. The findings were statistically and clinically significant. No clinically meaningful effect was observed with the other reagents. The activated partial thromboplastin time and thrombin time were not affected. Prolonged International Normalized Ratio patient values were an artifact caused by the interaction of daptomycin with the in-vitro prothrombin time test reagent; an in-vivo anticoagulant effect was not observed. Healthcare providers should consider a possible drug-laboratory test interaction if prolonged prothrombin time or elevated International Normalized Ratio values are observed in patients receiving daptomycin.

Community-phenotype-methicillin-resistant Staphylococcus aureus infections: a retrospective chart review of outcomes after treatment with daptomycin.

BACKGROUND: Daptomycin, a cyclic lipopeptide antibiotic, was approved by the US Food and Drug Administration (FDA) in September 2003 for the treatment of complicated skin and skin structure infections due to susceptible strains of certain gram-positive microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). In May 2006, daptomycin was approved by the FDA for treatment of bacteremia and right-sided endocarditis due to MRSA and methicillin-sensitive S aureus. OBJECTIVE: The aim of this study was to assess the use of daptomycin in community-phenotype (CP)-MRSA infections. METHODS: This was a retrospective chart review of data from patients enrolled in a postlabeling registry who received daptomycin for MRSA infections from January to December 2005. CP-MRSA was defined as MRSA susceptible to clindamycin and trimethoprim/sulfamethoxazole; all other phenotypes were considered other-phenotype MRSA (OP-MRSA). Success rates were calculated by dividing success (defined as cure plus improved) by success and failure (including non-evaluable patients). RESULTS: A database search identified 352 patients (100 patients with CP-MRSA [57 men; 43 women]; 252 patients with OP-MRSA [136 men, 116 women]) who met study criteria. Most patients (79.2%) received gram-positive antibiotics before daptomycin. Compared with OP-MRSA, a greater proportion of patients with CP-MRSA were <50 years of age (50.0% vs 35.7%; P = 0.014) and had fewer underlying diseases (mean [SD], 1.7 [1.3] vs 2.5 [1.5]; P < 0.001). Success rate, time to clinical response, and duration of therapy were similar in both groups. CONCLUSION: Daptomycin was found to be equally effective in treating CP-MRSA and OP-MRSA infections in this selected group of patients.

Effectiveness and duration of daptomycin therapy in resolving clinical symptoms in the treatment of complicated skin and skin structure infections.

OBJECTIVE: Compare the rapidity of the resolution of clinical signs and symptoms of complicated skin and skin structure infections (cSSSIs) caused by gram-positive organisms between daptomycin and comparator agents. PATIENTS AND METHODS: A subset of South African patients with gram-positive cSSSIs and no or one comorbid condition from two phase III clinical trials were included in the analysis. Patients were treated with daptomycin (n = 174) or comparator (penicillinase-resistant penicillins [n = 146] or vancomycin [n = 6]). The presence and severity of eight clinical signs and symptoms were evaluated at baseline, day 3 or 4 of treatment, end of therapy, and at test of cure (6-20 days after the last dose). RESULTS: Of the 326 patients included in this analysis, the clinical success rates between daptomycin and comparator treatments was comparable. Overall, the severity of symptoms in the daptomycin-treated patients improved more quickly (p = 0.04) than comparator treatment. At the day 3/4 evaluation, of the eight signs and symptoms, severity significantly decreased for induration (p = 0.03) and erythema (p = 0.05); a statistical trend was noted for necrotic tissue (p = 0.10) and edema (p = 0.10) in daptomycin-treated patients. Daptomycin treatment resulted in a shorter median duration of therapy than those receiving comparator treatment (7 vs. 8 days, p < 0.0001). Both treatments were well tolerated. CONCLUSION: Daptomycin produced a more rapid clinical improvement than comparators, as evidenced by significant reductions in the severity of induration and erythema, with a shorter duration of antibiotic therapy. However, this population was relatively young and healthy; therefore, these results may not be generalizable to all populations.

Efficacy of daptomycin in complicated skin and skin-structure infections due to methicillin-sensitive and -resistant Staphylococcus aureus: results from the CORE Registry.

OBJECTIVE: To characterize postmarketing clinical experience with daptomycin in treating complicated skin and skin-structure infections (cSSSIs) due to culture-confirmed MRSA and MSSA in real-life prescribing situations. RESEARCH DESIGN AND METHODS: The Cubicin Outcomes Registry and Experience 2004 (CORE 2004) is a multicenter observational registry involving 45 separate institutions, designed to characterize infection types, pathogens, and outcomes of patients who were treated with daptomycin. A subset analysis of the CORE 2004 data was conducted to characterize patients with cSSSI due to culture-confirmed MRSA and MSSA, but without bacteremia, endocarditis, osteomyelitis, or other significant infectious processes. Clinical information, including patient demographics, antibiotic treatments, and clinical outcome, was analyzed. Adverse event data were not collected in CORE 2004. MAIN OUTCOME MEASURE: Clinical success (cured or improved) or failure was assessed at the end of daptomycin treatment. RESULTS: A total of 165 patients were identified, including 145 patients (87.9%) with MRSA and 20 patients (12.1%) with MSSA infections. Most patients received daptomycin at a dosage of 4-6 mg/kg intravenously and at a frequency of once every 24 h. Daptomycin dosing frequency was adjusted to once every 48 h or thrice weekly in all seven patients who had received hemodialysis. Prior antibiotic therapy had been administered to 121/163 (74.2%) patients and concomitant antibiotic therapy to 65/165 (39.4%) of patients. Clinical success was achieved with daptomycin in 89.1% of patients overall, including 89.7% and 85.0% of those with MRSA and MSSA, respectively. Among patients with a successful outcome, the total days of daptomycin therapy (median days: MRSA = 13.0, MSSA = 11.0) and the days to clinical response (median days: MRSA = 3.5, MSSA = 2.0) were not significantly different for MRSA and MSSA patients (p = 0.27 and p = 0.15 respectively, median test). CONCLUSIONS: Given the limitations of this registry (which include its retrospective nature; limited numbers of MSSA patients; and lack of specific information on adverse events, type and duration of prior antibiotic therapy, timing and duration of concomitant antibiotic therapy, concomitant surgical interventions, and possible on-therapy dosing adjustments), daptomycin appeared effective in postmarketing clinical practice in the treatment of cSSSI caused by MRSA and MSSA.