Use Of Ceftaroline Research Articles

Ceftaroline for Central Nervous System Infections: Case Report of a Young Infant, and Scoping Review.

Managing health care acquired and device-associated intracranial infections in young children can be challenging given adverse antibiotic side effects and difficulties in achieving adequate central nervous system (CNS) antibiotic concentrations. Ceftaroline is a cephalosporin with a favorable safety profile and activity against methicillin-resistant Staphylococci and several Gram-negative organisms. Published data on the use of ceftaroline for CNS infections in children and adults are limited. We describe a 2-month-old infant with ventriculo-subgaleal shunt-associated methicillin-resistant Staphylococcus epidermidis ventriculitis, which was successfully treated with ceftaroline, in addition to vancomycin and rifampin. We conducted a scoping review of English-language literature retrieved from PubMed, EMBASE and Web of Science that assessed the use of ceftaroline for CNS infections. We identified 22 articles for inclusion in our review, which described 92 unique patients, of whom 2 were <21 years old. Ceftaroline was commonly used in conjunction with other antibiotics to treat infections caused by Staphylococcus aureus , coagulase-negative Staphylococci and Streptococcus pneumoniae . Most case reports described clinical success with ceftaroline, though small case series and cohort studies yielded mixed efficacy assessments. Adverse effects attributed to ceftaroline were rare and included reversible myelosuppression, eosinophilia, hepatotoxicity and nephrotoxicity. Pharmacokinetic/pharmacodynamic studies suggested similar CNS penetration through inflamed meninges as other beta lactam antibiotics. We identified a growing body of published evidence supporting the use of ceftaroline in combination with other agents for the treatment of CNS infections. In absence of clinical trials, additional real-world data are needed to define the efficacy and safety of ceftaroline for children and adults with CNS infections.

Evaluation of In-Vitro Activity of Ceftaroline Against Methicillin-Resistant Staphylococcus aureus Clinical Isolates.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital and community-acquired infections. Fewer drugs, such as vancomycin, teicoplanin, and daptomycin, are effective against it, but they come with high toxicity. Fifth-generation cephalosporins like ceftaroline and second-generation cefuroxime are effective against MRSA. Limited studies are available on ceftaroline resistance in the literature. This study was undertaken to determine ceftaroline resistance in MRSA in a tertiary care hospital in Eastern India. A cross-sectional, hospital-based study was carried out with MRSA isolates obtained from various clinical samples of patients. Identification of the isolates to the species level was performed by an automated Vitek system, and selected samples were genotypically confirmed by detecting the mecA gene via real-time PCR. Out of a total of 334 Staphylococcus aureus isolates examined in this study, the prevalence of MRSA was seen in 59.3% (198/334), and methicillin-sensitive Staphylococcus aureus was in 40.7% (136/334). Of the total 198 MRSA isolates, ceftaroline intermediate MRSA was seen in 8.6% (17/198), and ceftaroline sensitive MRSA was in 91.4% (181/198), respectively. Among the 17 ceftaroline intermediate MRSA isolates, 88.2% (15/17) showed aminimum inhibitory concentration (MIC) of 2 µg/ml, and 11.8% (2/17) showed an MIC of 3 µg/ml. All the remaining 91.4% (181/198) isolates were sensitive to ceftaroline and showed an MIC ≤1 µg/ml. Real-time PCR confirmed the presence of the mecA gene in MRSA isolates. In this present study, not a single isolate was resistant to ceftaroline, suggesting that it, being a safer drug, can be used in place of glycopeptides such as vancomycin or teicoplanin and linezolid, where resistance has already been detected. The rational use of ceftaroline could be useful in clinical settings, and further studies will confirm the findings.

Peri-transplant Treatment with Ceftaroline in Kidney Transplant Recipients at Risk of Donor-derived MRSA Infections: A Case Series

The rising prevalence of MDR pathogens has a significant impact on the recipients' outcome, as this increases the risk of graft complications and makes the management of the peri-transplant phase more difficult. Among the different MDR germs, Methicillin-resistant Staphylococcus aureus (MRSA) represents one of the most frequently isolated pathogens. We report for the first time the off-label use of Ceftaroline in six kidney transplant recipients with donor peritransplantation MRSA bacteremia at the Division of Kidney Transplant Unit of Federico II University Hospital of Naples, Italy, between September and December 2022. Each patient was followed up for the next three months after transplantation, monitoring the clinical and laboratory outcome, the risk of infection, and the efficacy and safety profile of the treatment performed. In the subsequent three months of follow-up to the transplant, none of the six patients showed donor-related infections. In particular, none of the six patients showed MRSA bacteremia or other related MRSA infections. In conclusion, our real-life experience shows that Ceftaroline could represent a valid therapeutic option in the management of solid organ transplant patients with a risk of donor-derived MRSA infection. However, despite the few cases considered, this approach deserves further investigation in ad hoc studies or clinical trials due to our positive results.

Risk of Neutropenia with the Use of Ceftaroline: A Review

Risk of Neutropenia with the Use of Ceftaroline: A Review

Clinical Outcomes of Ceftaroline Fosamil in the Treatment of Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia

Abstract Background Limited evidence exists in the management of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with ceftaroline as salvage therapy. This retrospective study aims to evaluate the use of ceftaroline as salvage therapy in the treatment of persistent MRSA bacteremia (MRSAB). Methods Electronic medical charts of patients who received ceftaroline for the treatment of persistent MRSAB at an academic, quaternary care medical center from January 1, 2015, to December 31, 2021, were reviewed for clinical cure, reinfection, prior antibiotic use, source of infection, microbiological culture clearance, patient mortality, and adverse effects. Primary endpoints included clinical and microbiological success, and secondary endpoints were recurrence of infection and 60-day all-cause mortality. Results Nineteen patient charts were identified, and 9 patients met the inclusion criteria for this analysis. Vancomycin or daptomycin was given for a median of 7 ± 2.3 days, respectively, before the initiation of ceftaroline. The total daily dose of ceftaroline ranged from 400 to 1800 mg depending on the patients' kidney function. Five patients achieved clinical cure and 4 patients died. No patients experienced a recurrence. Three patients (33%) experienced adverse effects while on ceftaroline therapy. Conclusions The use of ceftaroline in persistent MRSAB demonstrated microbiological cure, clinical cure, and minimal reinfection in the reviewed patient population. Ceftaroline may be a potential treatment option for patients with persistent MRSAB as salvage therapy.

Clinical results with the use of ceftaroline and ceftobiprole: real-life experience in a tertiary care hospital

Ceftaroline and ceftobiprole show activity against resistant Gram-positive cocci as well as good tolerability and are increasingly used in diverse infections. No comparative data on the efficacy and safety of ceftaroline and ceftobiprole in real-life are available. In this single-centre, observational, retrospective clinical study, the outcomes of patients treated with ceftaroline or ceftobiprole in our hospital were compared, assessing clinical data, use and drug exposure of study antibiotics, and outcomes. A total of 138 patients were included in this study, including 75 treated with ceftaroline and 63 treated with ceftobiprole. Patients treated with ceftobiprole had more comorbidities [median Charlson comorbidity index 5 (4-7) vs. 4 (2-6) for ceftaroline; P=0.003], a higher prevalence of multiple site infections (P < 0.001) and were more often treated empirically (P=0.004), whilst ceftaroline was more frequently used in patients with healthcare-related infections. No differences were observed in terms of hospital mortality, length of stay, and rates of clinical cure, improvement or failure. The only independent predictor of outcome was Staphylococcus aureus infection. Both treatments were generally well tolerated. In our real-life experience, ceftaroline and ceftobiprole, applied in different clinical scenarios, were comparable in terms of clinical efficacy and tolerability in a range of severe infections with variable aetiology and different levels of clinical severity. We believe our data may support the clinician in choosing the best option for each therapeutic setting.

Changes in the Use of Antibiotics for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Children: A 5-Year Retrospective, Single Center Study

Monitoring antibiotic use in the pediatric population is a challenge, especially when determining a relationship between specific pathogens, infections, and antibiotic use. We retrospectively analyzed the consumption of anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs from 2017 to 2021 at Istituto Giannina Gaslini by means of defined daily dose (DDD) adopted for adults by World Health Organization. We observed a statistically significant increase in the use of daptomycin and ceftaroline, combined with a decrease in the use of vancomycin. In the same period, we observed an increase in the proportion of bloodstream infections due to MRSA with vancomycin minimally inhibitory concentration (MIC mg/L) = 1, that represented the 100% of cases in 2021. This aspect was combined with the observation that in the 59% of cases, where vancomycin plasma concentrations were evaluated, it was not possible to achieve a ratio of the 24-h area under the concentration-time curve and MIC (AUC0-24/MIC) of vancomycin ≥ 400 mg/L. This study confirms that DDD can be used in pediatrics to monitor antibiotic consumption in relationship with infections epidemiology. Moreover, it describes the presence of vancomycin MIC creep for MRSA also in pediatrics and the difficulties in obtaining effective vancomycin plasma concentrations in children.

Ceftaroline and Daptomycin Combination Antibiotic Therapy for a Methicillin-Resistant Staphylococcus Aureus Liver Abscess in a Premature Infant.

Staphylococcus aureus is a common bacterial etiology for infections in the neonatal intensive care unit (NICU). Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) can be difficult to treat, even when good source control is obtained. There are few data on treatment of MRSA abscess in the neonatal population. Vancomycin, clindamycin, daptomycin, ceftaroline, and linezolid are often used to treat MRSA infections in pediatric patients. Daptomycin and ceftaroline have been studied in adults as a salvage therapy for refractory MRSA infections. Few data exist on combination therapy for treatment of MRSA infection in neonatal or premature infant patients. This case report describes the successful use of intravenous (IV) daptomycin (6 mg/kg IV every 12 hours) plus ceftaroline (8 mg/kg IV every 8 hours) for 18 days after failure of daptomycin monotherapy to treat multiple hepatic abscesses and an infected thrombus caused by MRSA in a premature female born at 30 weeks of gestation. The patient had increased abscess size after daptomycin monotherapy and treatment was changed to combination therapy. With addition of the ceftaroline, the abscesses resolved entirely on ultrasonography within 3 weeks. While combination therapy was effective in this patient, additional research is needed to determine the most appropriate use for combination therapy for treatment of MRSA infections in the premature infant and neonatal population.

An Update on Treatment Options for Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia: A Systematic Review.

Since the last century, methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has become a major global and public health concern not only in terms of morbidity and mortality but also the duration of hospital stay, healthcare cost, and antimicrobial choices. Especially alarming is the growing antimicrobial resistance due to their misuse and overuse, which has led the world to be exhausted of its effective antibiotic resources. In this review article, we sought to figure out the most efficacious antimicrobial agents to treat MRSA-related bloodstream infections. We compared the data from reviewing reports from 2017 to 2022 and summarized their comparative efficacy and cost-effectiveness. Although we focused on vancomycin and daptomycin, which are the current Infectious Disease Society Of America (IDSA)-recommended antibiotics for MRSA bacteremia treatment, a deep dive into the newer agents revealed better efficacy and treatment outcome in the combination of ceftaroline (β-lactam) with daptomycin compared to traditional standard monotherapy (vancomycin/daptomycin monotherapy). Also, the IDSA recommended high-dose daptomycin (8-10 mg/kg) therapy for MRSA bacteremia treatment to be more effective in cases with vancomycin-reduced susceptibility. Moreover, we did not find any trial or study describing the use of ceftaroline as a monotherapy to compare its efficacy in MRSA bacteremia with the current standard therapy. The upshot is that we need more large-scale clinical trials exploring in-depth effectiveness and adverse effects to decide on newer agents like β-lactams to use as routine therapy for MRSA bacteremia.

Multicenter Cohort Study of Ceftaroline Versus Daptomycin for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection.

BackgroundObservational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin.MethodsMulticenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied.ResultsTwo hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, –5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001).ConclusionsNo difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.

686. Comparing Treatments of Methicillin-Resistant Staphylococcus aureus Infective Endocarditis by People Who Inject Drugs

Abstract Background People who inject drugs (PWID) are at high risk for infective endocarditis (IE) with high-mortality pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). Stigma against PWID may cause differences in treatment and outcomes between these patients infected with MRSA IE. Methods Single center retrospective cohort study from August 2006 to February 2021 that includes adult patients diagnosed with IE. Primary outcomes included 90-day all-cause mortality, 60-day MRSA recurrence, 60-day readmission, and hospital length of stay (LOS). Statistical analysis was performed by chi-square, t-test, and Mann-Whitney-U as appropriate. Results A total of 214 patients were diagnosed with MRSA IE; 89 PWID and 125 non-PWID. The mean (SD) age was 47.4±12.4 years (PWID) vs 59.3 ±16.0 years (non-PWID) (p&amp;lt; 0.001). Patients were primarily male (56%), but differed in terms of race 34% African-American (AA) (PWID) vs 66% AA (non-PWID) (p&amp;lt; 0001). Mean APACHE II scores differed between groups: 16(±9.9) (PWID) vs 19(±8.1) (non-PWID) (p&amp;lt; 0.008). Among patients who cleared bacteremia, mean (SD) duration was 5.7(±3.9) days and was not significant between groups (p&amp;lt; 0.64). Valve-type was 93% native and 7% prosthetic and not different between groups (p&amp;lt; 0.16). Infectious Diseases consult did not differ at 96% overall (p&amp;lt; 0.31), but pursuit of source control nearly reached significance at 27% for PWID vs 41% non-PWID (p&amp;lt; 0.06). Similarly, use of combination therapy daptomycin and ceftaroline was nearly significant: 21% (PWID) vs 12% (non-PWID) (p&amp;lt; 0.09). Odds ratio of PWID and combination therapy remained non-significant after regression: 0.39(0.14-1.1,p&amp;lt; 0.07). Primary 90-day mortality was lower in PWID vs non-PWID (15% vs 30%) respectively (p&amp;lt; 0.01), but did not differ in 60-day MRSA recurrence (p&amp;lt; 1.0) at 9%, 60-day readmission (p&amp;lt; 1.0) at 33%, or median LOS (IQR) (p&amp;lt; 0.46) at 15 (10-24) days overall. Conclusion While PWID are significantly younger, less critically ill, and have lower mortality compared to non-PWID, they have similar LOS, MRSA recurrence, and readmission rates. Analyses suggest a potential difference in the pursuit of source control and combination therapy among PWID, however more studies may be needed to achieve significance. Disclosures Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

Impact on in-hospital mortality of ceftaroline versus standard of care in community-acquired pneumonia: a propensity-matched analysis

The purpose of this study is to evaluate the in-hospital mortality of community-acquired pneumonia (CAP) treated with ceftaroline in comparison with standard therapy. This was a retrospective observational study in two centers. Hospitalized patients with CAP were grouped according to the empiric regimen (ceftaroline versus standard therapy) and analyzed using a propensity score matching (PSM) method to reduce confounding factors. Out of the 6981 patients enrolled, 5640 met the inclusion criteria, and 89 of these received ceftaroline. After PSM, 78 patients were considered in the ceftaroline group (cases) and 78 in the standard group (controls). Ceftaroline was mainly prescribed in cases with severe pneumonia (67% vs. 56%, p = 0.215) with high suspicion of Staphylococcus aureus infection (9% vs. 0%, p = 0.026). Cases had a longer length of hospital stay (13 days vs. 10 days, p = 0.007), while an increased risk of in-hospital mortality was observed in the control group compared to the case group (13% vs. 21%, HR 0.41; 95% CI 0.18 to 0.62, p = 0.003). The empiric use of ceftaroline in hospitalized patients with severe CAP was associated with a decreased risk of in-hospital mortality.

Use of Ceftaroline in Hospitalized Patients with and without COVID-19: A Descriptive Cross-Sectional Study.

A single-center cross-sectional study was conducted to describe the use of ceftaroline in a large teaching hospital in Northern Italy, during a period also including the first months of the coronavirus disease 2019 (COVID-19) pandemic. The primary objective was to describe the use of ceftaroline in terms of indications and characteristics of patients. A secondary objective was to describe the rate of favorable clinical response in patients with bloodstream infections (BSI) due to methicillin-resistant Staphylococcus aureus (MRSA-BSI) receiving ceftaroline. Overall, 200 patients were included in the study. Most of them had COVID-19 (83%, 165/200) and were hospitalized in medical wards (78%, 155/200). Included patients with COVID-19 pneumonia were given empirical ceftaroline in the suspicion of bacterial co-infection or superinfection. Among patients with MRSA-BSI, ceftaroline was used as a first-line therapy and salvage therapy in 25% (3/12) and 75% (9/12) of cases, respectively, and as a monotherapy or in combination with daptomycin in 58% (7/12) and 42% (5/12) of patients, respectively. A favorable response was registered in 67% (8/12) of patients. Improving etiological diagnosis of bacterial infections is essential to optimize the use of ceftaroline in COVID-19 patients. The use of ceftaroline for MRSA-BSI, either as a monotherapy or in combination with other anti-MRSA agents, showed promising rates of favorable response.

Major Aspects of Detection and Monitoring of Adverse Reactions Associated with Cephalosporin Antibiotic Treatment

Widespread use of cephalosporin antibiotics in clinical practice calls for greater attention to the risk of adverse drug reactions. Information on serious or unexpected adverse events reported during post-marketing experience is submitted to national and international pharmacovigilance databases. Analysis of these reports helps to identify new adverse drug reactions.The aim of the study was to analyse the safety profile of cephalosporin antibiotics based on spontaneous reports in the international VigiBase database.Materials and methods: the analysis of the adverse reaction profile of cephalosporin antibiotics was based on MedDRA system organ classes and included spontaneous reports submitted to VigiBase from the moment of its creation until August 2020.Results: the authors identified the most clinically significant adverse reactions for different cephalosporin generations. They compared and analysed information on adverse events in VigiBase and in patient information leaflets of medicinal products authorised in the Russian Federation. It was demonstrated that some serious events described in VigiBase spontaneous reports for V-generation cephalosporins are not included in the “Side effects” section of the patient information leaflets. According to VigiBase, the use of ceftaroline was associated with the development of generalised exfoliative dermatitis, Stevens–Johnson syndrome, tubulointerstitial nephritis, while the use of ceftolozane was associated with acute kidney injury, renal insufficiency, sepsis, pneumonia, and respiratory insufficiency.Conclusion: reporting of unexpected and serious adverse drug reactions to cephalosporin antibiotics is an important task of healthcare practitioners. Availability of information on class-specific and generation-specific serious adverse reactions will help predict and prevent their development.

225. Antimicrobial Stewardship Program Interventions Targeting Intravenous Vancomycin Use at a Community Hospital Improves Prescribing and Safety

BackgroundIntravenous vancomycin (VAN) continues to be a workhorse for suspected or documented methicillin-resistant Staphylococcus aureus (MRSA) infections. VAN over-prescribing, and suboptimal dosing or monitoring can be detrimental to efficacy, safety, and resource utilization. A local antimicrobial stewardship program (ASP) was implemented in September 2015 as an expansion of a pre-existing health-system ASP. The local ASP included an infectious diseases (ID) pharmacist, partial FTE ID physician, ASP software, and a goal to decrease inappropriate vancomycin use and improve safety.MethodsWe performed a serial cross-sectional study assessing the impact of ASP interventions on VAN consumption and AKI incidence at a single-center community hospital from October 2015 through March 2018. ASP interventions included a revised vancomycin dosing and monitoring guideline, education, and prospective audit and feedback by clinical pharmacists working under the guidance of ID pharmacist and physician. Antibiotic days of therapy (DOT) were tracked and reported quarterly with Theradoc® software. Acute kidney injury was defined as an increase of ≥0.5 mg/dL or 50% in serum creatinine from baseline in all hospitalized patients with baseline <2 mg/dL.ResultsFigure 1 demonstrates MRSA antibiotic utilization and AKI over time. VAN use declined from a peak quarterly use of 119 DOT/1,000 PD to a minimum of 74 DOT/1,000 PD (37.8% decrease). During the same timeframe AKI/1,000 PD decreased over 50%. R2 values of the trends are 76.5% and 83.1%, respectively. The use of VAN alternatives daptomycin (DAP), linezolid (LNZ), and ceftaroline (CPT) remained stable. There were 809 ASP recommendations made regarding VAN over-prescribing (primarily to de-escalate or discontinue VAN therapy) and 340 ID pharmacist interventions to improve VAN dosing and monitoring.Figure 1.ConclusionASP initiatives, education, and interventions were associated with reduced VAN use and reduction in AKI at a community hospital.Disclosures All authors: No reported disclosures.

Experience with ceftaroline for treatment of methicillin-resistant Staphylococcus aureus pneumonia in a community hospital

ABSTRACTBackground: Methicillin-resistant Staphylococcus aureus (MRSA) is an organism causing significant mortality and morbidity with nosocomial infections. Ceftaroline is a new cephalosporin antibiotic that has activity against MRSA. In the USA, this antibiotic has not been approved for use in pneumonia caused by MRSA.Objectives: To review the use of ceftaroline in MRSA pneumonia in a US hospital and evaluate its clinical success.Methods: A retrospective study was conducted in an urban community hospital assessing the use of ceftaroline for MRSA pneumonia.Results: The clinical success was comparable to the currently approved treatment for MRSA pneumonia.Conclusion: The results of our study showed a favorable result for the treatment of MRSA pneumonia. Well-designed studies need to be performed for further validation of these results.

Evaluation of a Second-Sign Process for Antimicrobial Prior Authorization.

A second-sign prospective restriction of select broad-spectrum antimicrobials was fully implemented in January 2015 as a pediatric antimicrobial stewardship program (ASP) initiative to help ensure the most appropriate empiric use of ceftaroline, cefepime, fidaxomicin, linezolid, and vancomycin (intravenous). The objective of this evaluation is to assess the effectiveness of a forced second-sign process in the electronic medical record as a pediatric ASP strategy. We anticipated that the second-sign process for antibiotics would increase the appropriateness of empiric antibiotic use, as defined by preapproved criteria, clinical pathways, national guidelines, and pediatric-specific infectious diseases reference texts, while not causing significant delay in the initial administration of antibiotic therapy. This was a retrospective before and after intervention chart review conducted from July 2014 to June 2015. The study was conducted at a 187-bed, freestanding teaching children's hospital that included the following: level-1 pediatric trauma center, 18-bed pediatric intensive care unit, and 32-bed neonatal intensive care unit. A total of 1178 orders were identified, and 389 met inclusion criteria. The vast majority of second-sign orders were for vancomycin (92%), 61% were written for males, and the median age was 6 years old. Appropriateness of second-sign restricted antibiotic use significantly increased after second-sign implementation (84.5% to 92.9%, P = .01). The secondary outcome of time from initial order entry to medication administration was not different between the before and after groups (median time, 184.5 [interquartile range, 110.25-280.75] vs 174 [interquartile range, 104-228] minutes; P = .342). The use of a second-sign approval process for antimicrobial restriction can lead to increased appropriateness of antibiotic use at a pediatric hospital, without causing a delay in administration.

Current Clinical Trials on the Use of Ceftaroline in the Pediatric Population.

The rate of antibiotic resistance in children continues to rise requiring the use of new antibiotics. Ceftaroline fosamil, a newer-generation cephalosporin, was recently approved for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia in children aged >2months. Ceftaroline provides coverage against staphylococcal and streptococcal infections, including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. Pediatric dosing differs from adult dosing, but it maintains a similar pharmacokinetic profile and offers similar efficacy in terms of time above the minimum inhibitory concentration as compared to the adult population. The clinical safety and efficacy of this antibiotic has been assessed in three pediatric clinical trials that led to its approval by the US Food and Drug Administration, and each trial is described within this review. This article will also discuss the ongoing trials assessing the possibility of expanding the indications of this antibiotic to late-onset sepsis, meningitis and osteomyelitis in the pediatric population.

Ceftaroline for Severe Methicillin-Resistant Staphylococcus aureus Infections: A Systematic Review

Ceftaroline is approved by the Food and Drug Administration for acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia, including cases with concurrent bacteremia. Use for serious methicillin-resistant Staphylococcus aureus (MRSA) infections has risen for a multitude of reasons. The aim of this article is to review the literature evaluating clinical outcomes and safety of ceftaroline prescribed for serious MRSA infections. We conducted a literature search in Ovid (Medline) and PubMed for reputable case reports, clinical trials, and reviews focusing on the use of ceftaroline for treatment of MRSA infections. Twenty-two manuscripts published between 2010 and 2016 met inclusion criteria. Mean clinical cure was 74% across 379 patients treated with ceftaroline for severe MRSA infections. Toxicities were infrequent. Ceftaroline treatment resulted in clinical and microbiologic cure for severe MRSA infections. Close monitoring of hematological parameters is necessary with prolonged courses of ceftaroline.

Ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus bacteremia.

The utility of ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) is reviewed. Ceftaroline was originally approved for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSIs) but recently received an additional approval for the treatment of S. aureus bacteremia (SAB) associated with ABSSSIs. Ceftaroline has demonstrated efficacy for the treatment of MRSAB, including isolates with elevated minimum inhibitory concentrations to conventional therapy when used alone or in combination with other agents. In multiple studies, ceftaroline has displayed rapid bloodstream eradication, even in the setting of refractory MRSAB or infective endocarditis. The clinical resolution of MRSAB or SAB in patients who received ceftaroline ranged from 31.0% to 83.3%; studies used varying definitions for clinical resolution and included differing proportions of patients with endocarditis. The use of ceftaroline in treatment-refractory patients and assorted populations makes absolute effectiveness difficult to determine. Ceftaroline has been shown to be effective in patients who have not responded to other agents for MRSAB, making it an attractive option for such patients. Although the approved dosing regimen for ceftaroline fosamil is 600 mg every 12 hours for patients with normal renal function for the treatment of ABSSSIs and CABP, there is some debate about whether more frequent doses (i.e., every 8 hours) are needed for MRSAB. Ceftaroline has been used to successfully treat SAB, including endocarditis. Therapy with ceftaroline may be considered when antibiotic resistance or previous treatment failure precludes the use of first-line agents.