A Real-world Multicenter Outpatient Experience of Ceftolozane/Tazobactam.

Background: Ceftolozane/tazobactam (C/T) is indicated for the treatment of complicated intra-abdominal infection (IAI), complicated urinary tract infection (UTI), and hospital-acquired/ventilator-associated bacterial pneumonia caused by susceptible bacteria. As real-world data are limited, we report utilization and associated outcomes of C/T use in the outpatient setting. Methods: This is a multicenter, retrospective study of patients who received C/T between May 2015 and December 2020. Demographics, infection types, C/T utilization characteristics, microbiology, and health care resource utilization were collected. Clinical success was defined as complete or partial symptom resolution at completion of C/T. Persistent infection and discontinuation of C/T were deemed nonsuccess. Logistic regression analysis was used to identify predictors associated with clinical outcomes. Results: A total of 126 patients (median age, 59 years; 59% male; median Charlson index, 5) from 33 office infusion centers were identified. Infection types included 27% bone and joint infection (BJI), 23% UTI, 18% respiratory tract infection (RTI), 16% IAI, 13% complicated skin and soft tissue infection (cSSTI), and 3% bacteremia. The median daily dose of C/T was 4.5 g, primarily administered via elastomeric pumps as intermittent infusion. The most common gram-negative pathogen was P. aeruginosa (63%), 66% of which was multidrug-resistant and 45% carbapenem-resistant. Enterobacterales was identified in 26% of isolates, of which 44% were extended-spectrum beta-lactamase producers. The overall clinical success rate of C/T was 84.7%. Nonsuccessful outcomes were due to persistent infections (9.7%) and drug discontinuations (5.6%). Conclusions: C/T was successfully used in the outpatient setting to treat a variety of serious infections with a high prevalence of resistant pathogens.

Attenuated early pregnancy weight gain by prenatal lifestyle interventions does not prevent gestational diabetes in the LIFE-Moms consortium.

AIMS: To examine the effect of lifestyle (diet and physical activity) interventions on the prevalence of GDM, considering the method of GDM ascertainment and its association with early pregnancy characteristics and maternal and neonatal outcomes in the LIFE-Moms consortium. METHODS: LIFE-Moms evaluated the effects of lifestyle interventions to optimize gestational weight gain in 1148 pregnant women with BMI ≥ 25 kg/m2 and without known diabetes at enrollment, compared with standard care. GDM was assessed between 24 and 31-weeks gestation by a 2-hour, 75-gram OGTT or by local clinical practice standards. RESULTS: Lifestyle interventions initiated prior to 16 weeks reduced early excess GWG compared with standard care (0.35 ± 0.24 vs 0.43 ± 0.26 kg per week, p=<0.0001) but did not affect GDM diagnosis (11.1% vs 11.6%, p = 0.91). Using the 75-gram, 2-hour OGTT, 13. 0% of standard care and 11.0% of the intervention group had GDM by the IADPSG criteria (p = 0.45). The 'type of diagnostic test' did not change the result (p = 0.86). Women who developed GDM were significantly heavier, more likely to have obesity, and more likely to have dysglycemia at baseline. CONCLUSION: Moderate-to-high intensity lifestyle interventions grounded in behavior change theory initiated between 9 and 16-weeks gestation did not affect the prevalence of GDM despite reducing early GWG. CLINICALTRIALS.GOV: NCT01545934, NCT01616147, NCT01771133, NCT01631747, NCT01768793, NCT01610752, NCT01812694.

One-year postpartum anthropometric outcomes in mothers and children in the LIFE-Moms lifestyle intervention clinical trials.

BACKGROUND/OBJECTIVES: Excess gestational weight gain (GWG) is a risk factor for maternal postpartum weight retention and excessive neonatal adiposity, especially in women with overweight or obesity. Whether lifestyle interventions to reduce excess GWG also reduce 12-month maternal postpartum weight retention and infant weight-for-length z score is unknown. Randomized controlled trials from the LIFE-Moms consortium investigated lifestyle interventions that began in pregnancy and tested whether there was benefit through 12 months on maternal postpartum weight retention (i.e., the difference in weight from early pregnancy to 12 months) and infant-weight-for-length z scores. SUBJECTS/METHODS: In LIFE-Moms, women (N = 1150; 14.1 weeks gestation at enrollment) with overweight or obesity were randomized within each of seven trials to lifestyle intervention or standard care. Individual participant data were combined and analyzed using generalized linear mixed models with trial entered as a random effect. The 12-month assessment was completed by 83% (959/1150) of women and 84% (961/1150) of infants. RESULTS: Compared with standard care, lifestyle intervention reduced postpartum weight retention (2.2 ± 7.0 vs. 0.7 ± 6.2 kg, respectively; difference of -1.6 kg (95% CI -2.5, -0.7; p = 0.0003); the intervention effect was mediated by reduction in excess GWG, which explained 22% of the effect on postpartum weight retention. Lifestyle intervention also significantly increased the odds (OR = 1.68 (95% CI, 1.26, 2.24)) and percentage of mothers (48.2% vs. 36.2%) at or below baseline weight at 12 months postpartum (yes/no) compared with standard care. There was no statistically significant treatment group effect on infant anthropometric outcomes at 12 months. CONCLUSIONS: Compared with standard care, lifestyle interventions initiated in pregnancy and focused on healthy eating, increased physical activity, and other behavioral strategies resulted in significantly less weight retention but similar infant anthropometric outcomes at 12 months postpartum in a large, diverse US population of women with overweight and obesity.

Lifestyle Interventions Limit Gestational Weight Gain in Women with Overweight or Obesity: LIFE-Moms Prospective Meta-Analysis.

OBJECTIVE: This study aimed to evaluate the effects of varied lifestyle intervention programs designed to ameliorate excess gestational weight gain (GWG) in pregnant women with overweight or obesity compared with standard care, including effects on pregnancy outcomes. METHODS: Seven clinical centers conducted separate randomized clinical trials to test different lifestyle intervention strategies to modify GWG in diverse populations. Eligibility criteria, specific outcome measures, and assessment procedures were standardized across trials. The results of the separate trials were combined using an individual-participant data meta-analysis. RESULTS: For the 1,150 women randomized, the percent with excess GWG per week was significantly lower in the intervention group compared with the standard care group (61.8% vs. 75.0%; odds ratio [95% CI]: 0.52 [0.40 to 0.67]). Total GWG from enrollment to 36 weeks' gestation was also lower in the intervention group (8.1 ± 5.2 vs. 9.7 ± 5.4 kg; mean difference: -1.59 kg [95% CI:-2.18 to -0.99 kg]). The results from the individual trials were similar. The intervention and standard care groups did not differ in preeclampsia, gestational diabetes, cesarean delivery, or birth weight. CONCLUSIONS: Behavioral lifestyle interventions focusing primarily on diet and physical activity among women with overweight and obesity resulted in a significantly lower proportion of women with excess GWG. This modest beneficial effect was consistent across diverse intervention modalities in a large, racially and socioeconomically diverse US population of pregnant women.

Implementing a Breastfeeding Toolkit for Nursing Education.

All health professional organizations recommend exclusive breastfeeding for at least 6 months, with continued breastfeeding for 1 year or more after birth. Women cite lack of support from health professionals as a barrier to breastfeeding. Meanwhile, breastfeeding education is not considered essential to basic nursing education and students are not adequately prepared to support breastfeeding women. Therefore, a toolkit of comprehensive evidence-based breastfeeding educational materials was developed to provide essential breastfeeding knowledge. A study was performed to determine the effectiveness of the breastfeeding toolkit education in an associate degree nursing program. A pretest/posttest survey design with intervention and comparison groups was used. One hundred fourteen students completed pre- and posttests. Student knowledge was measured using a 12-item survey derived with minor modifications from Marzalik's 2004 instrument measuring breastfeeding knowledge. When pre- and posttests scores were compared within groups, both groups' knowledge scores increased. A change score was calculated with a significantly higher mean score for the intervention group. When regression analysis was used to control for the pretest score, belonging to the intervention group increased student scores but not significantly. The toolkit was developed to provide a curriculum that demonstrates enhanced learning to prepare nursing students for practice. The toolkit could be used in other settings, such as to educate staff nurses working with childbearing families.

Real-world daptomycin use across wide geographical regions: results from a pooled analysis of CORE and EU-CORE.

BACKGROUND: Pooled data from two large registries, Cubicin(®) Outcomes Registry and Experience (CORE; USA) and European Cubicin(®) Outcomes Registry and Experience (EU-CORE; Europe, Latin America, and Asia), were analyzed to determine the characteristics and clinical outcomes of daptomycin therapy in patients with Gram-positive infections across wide geographical regions. METHODS: Patients receiving at least one dose of daptomycin between 2004 and 2012 for the treatment of Gram-positive infections were included. Clinical success was defined as an outcome of 'cured' or 'improved'. Post-treatment follow-up data were collected for a subset of patients (CORE: osteomyelitis and orthopedic foreign body device infection; EU-CORE: endocarditis, intracardiac/intravascular device infection, osteomyelitis, and orthopedic device infection). Safety was assessed for up to 30 days after daptomycin treatment. RESULTS: In 11,557 patients (CORE, 5482; EU-CORE, 6075) treated with daptomycin (median age, 62 [range, 1-103] years), the most frequent underlying conditions were cardiovascular disease (54.7 %) and diabetes mellitus (28.0 %). The most commonly treated primary infections were complicated skin and soft tissue infection (cSSTI; 31.2 %) and bacteremia (21.8 %). The overall clinical success rate was 77.2 % (uncomplicated SSTI, 88.3 %; cSSTI, 81.0 %; osteomyelitis, 77.7 %; foreign body/prosthetic infection (FBPI), 75.9 %; endocarditis, 75.4 %; and bacteremia, 69.5 %). The clinical success rate was 79.1 % in patients with Staphylococcus aureus infections (MRSA, 78.1 %). An increasing trend of high-dose daptomycin (>6 mg/kg/day) prescribing pattern was observed over time. Clinical success rates were higher with high-dose daptomycin treatment for endocarditis and FBPI. Adverse events (AEs) and serious AEs possibly related to daptomycin therapy were reported in 628 (5.4 %) and 133 (1.2 %) patients, respectively. CONCLUSIONS: The real-world data showed that daptomycin was effective and safe in the treatment of various Gram-positive infections, including those caused by resistant pathogens, across wide geographical regions.

ASHP therapeutic position statement on strategies for identifying and preventing pneumococcal resistance.

The incidence of MDRSP continues to increase, causing significant morbidity and mortality. Health care providers should seize the opportunity to promote the judicious use of antimicrobials and vaccinate patients with the pneumococcal vaccines as a means to lessen this significant health problem. Pharmacists are poised to play a key role in patient care by assessing for the need and administering vaccines in compliance with the current guidelines. A pharmacist should have a key role on the antimicrobial stewardship team.

In vitro 24-hour time-kill studies of vancomycin and linezolid in combination versus methicillin-resistant Staphylococcus aureus.

Many clinicians are trying unique strategies, including vancomycin and linezolid in combination, for treatment of patients who do not respond to conventional therapy against methicillin (meticillin)-resistant Staphylococcus aureus. In our study, which illustrated in vitro activity only, no synergistic activity was seen when the two agents were combined. Conversely, antagonistic activity occurred in three of five strains when linezolid was added to vancomycin. Our results indicate that vancomycin and linezolid in combination should be avoided.

Azithromycin for the secondary prevention of coronary artery disease: a meta-analysis.

PURPOSE: A meta-analysis of randomized, controlled trials that evaluated the effect of the macrolide antibiotic, azithromycin, on clinical outcomes in patients with coronary artery disease (CAD) was conducted. METHODS: A systematic literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews was conducted using specific search terms. Randomized, controlled trials comparing azithromycin or placebo in secondary CAD patients with adequately reported data on mortality and clinical cardiac endpoints were included. A random-effects model was used. RESULTS: Six studies (n=13,778) met the inclusion criteria. The trials varied in their design. On meta-analysis, azithromycin resulted in a nonsignificant reduction in mortality versus placebo (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.77-1.09; p=0.31). Four trials reported the rate of nonfatal myocardial infarction (MI). Azithromycin did not have an effect on the rate of nonfatal MI versus placebo (OR, 0.95; 95% CI, 0.80-1.13; p=0.57). Five trials reported rates of hospitalization in which no significant difference was seen with azithromycin versus placebo (OR, 0.97; 95% CI, 0.80-1.17; p=0.76). Six trials were used to evaluate the composite cardiovascular endpoint. Again, no significant benefit was seen with azithromycin versus placebo (OR, 0.93; 95% CI, 0.84-1.03; p=0.218). CONCLUSION: Meta-analysis showed that azithromycin does not appear to reduce the frequency of recurrent cardiac events in patients with CAD. Results from ongoing trials may clarify the role of azithromycin in the secondary prevention of coronary events.