ppi-0903 and Bacteremia

This exploratory pooled analysis assessed the efficacy and safety of ceftaroline fosamil and comparators across six phase III clinical trials in adults with community-acquired pneumonia (CAP) or complicated skin and soft-tissue infection (cSSTI) and secondary bacteraemia.. In each trial, FOCUS 1 and 2 (CAP), Asia CAP trial, CANVAS 1 and 2 (cSSTI) and COVERS (cSSTI), patients were randomised to ceftaroline fosamil [600 mg q12h by 1-h i.v. infusion, except in COVERS (600 mg q8h by 2-h i.v. infusion), adjusted for renal function] or comparator. Efficacy assessments included clinical and microbiological responses at test-of-cure visit [microbiological modified intent-to-treat (mMITT) population]. Safety outcomes were assessed.. The pooled mMITT population comprised 1976 patients, of whom 138 had baseline bacteraemia (ceftaroline fosamil, n = 72; comparator, n = 66). Predominant baseline blood pathogens were Staphylococcus aureus (n = 29), Streptococcus pneumoniae (n = 19) and other streptococci (n = 12). Clinical cure rates in bacteraemic patients were 55/72 (76.4%) and 51/66 (77.3%) for ceftaroline fosamil and comparators, respectively, and in non-bacteraemic patients were 822/966 (85.1%) and 717/872 (82.2%). Favourable microbiological response rates in bacteraemic patients were 56/72 (77.8%) for ceftaroline fosamil and 54/66 (81.8%) for comparators, and in non-bacteraemic patients were 825/966 (85.4%) and 719/872 (82.5%). Adverse events in bacteraemic patients were consistent with the known ceftaroline fosamil safety profile or the underlying indications.. These pooled clinical and microbiological efficacy data demonstrate generally favourable outcomes for ceftaroline fosamil in patients with CAP or cSSTI and secondary bacteraemia. [Trial Registration: NCT00621504, NCT00509106; NCT01371838; NCT00424190, NCT00423657; NCT01499277].

Topics: Adult; Bacteremia; Ceftaroline; Cephalosporins; Clinical Trials, Phase III as Topic; Community-Acquired Infections; Humans; Pneumonia; Soft Tissue Infections; Treatment Outcome

Vancomycin and daptomycin are options for the initial treatment of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Treatment options for persistent MRSA bacteremia or bacteremia due to vancomycin-intermediate or vancomycin-resistant strains include daptomycin, ceftaroline, and combination therapies. There is a critical need for high-level evidence from clinical trials to allow optimally informed decisions in the treatment of MRSA bacteremia.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Clinical Trials as Topic; Daptomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Vancomycin

Ceftaroline fosamil is a fifth-generation cephalosporin with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. It has been approved by the EMA and FDA for the treatment of adults and children with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). However, ceftaroline fosamil has a broad spectrum of activity, and a good safety and tolerability profile, so is frequently used off-label. The aim of this systematic review was to summarize the safety and efficacy of off-label use of ceftaroline. The review was conducted according to PRISMA guidelines. MEDLINE, EMBASE and CENTRAL databases (2010-2018) were searched using as the main term ceftaroline fosamil and its synonyms in combination with names of infectious diseases of interest. A total of 21 studies with 1901 patients were included: the most common off-label indications for ceftaroline use were bacteremia (n=595), endocarditis (n=171), osteoarticular infections (n=368), hospital-acquired pneumonia (n=115) and meningitis (n=23). The most common reasons for off-label use were persistent or recurrent infection after standard treatment or non-susceptibility to vancomycin and daptomycin. Clinical success was evaluated in 933 patients, and 724 (77%) of these reached this positive outcome. Incidence of adverse events (AEs) was reported in 11 studies. In 83 (9%) cases there were AEs related to the use of ceftaroline; the most common reported AEs were nausea, vomiting, diarrhea, rash and neutropenia. The review results show that ceftaroline may be used in clinical settings other than those currently approved; however, the use of ceftaroline in these contexts deserves further investigation.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Community-Acquired Infections; Cross Infection; Endocarditis, Bacterial; Healthcare-Associated Pneumonia; Humans; Meningitis; Off-Label Use

The utility of ceftaroline for the treatment of methicillin-resistant. 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. 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.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Humans; Methicillin-Resistant Staphylococcus aureus; Retrospective Studies; Staphylococcal Infections; Treatment Outcome

This article reviews recent clinical evidence for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Vancomycin remains the initial antibiotic of choice for the treatment of patients with MRSA bacteremia and endocarditis due to isolates with vancomycin minimum inhibitory concentration ≤2 μg/mL, whereas daptomycin is an effective alternative, and ceftaroline seems promising. Treatment options for persistent MRSA bacteremia or bacteremia due to vancomycin-intermediate or vancomycin-resistant strains include daptomycin, ceftaroline, and combination therapies. There is a critical need for high-level evidence from clinical trials to allow optimally informed decisions in the treatment of MRSA bacteremia and endocarditis.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Vancomycin

To summarize published data regarding the use of ceftaroline as salvage monotherapy for persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia.. PubMed (January 1980-June 2016) was searched using combinations of the search terms methicillin-resistant Staphylococcus aureus, MRSA, bacteremia, ceftaroline, refractory, and persistent Supplemental references were generated through review of identified literature citations.. Available English-language, full-text articles pertaining to the use of ceftaroline for persistent MRSA bacteremia (MRSAB) were included.. The PubMed search yielded 23 articles for evaluation. There are no randomized controlled trials to date-only case series and reports. Four retrospective case series detailing the use of ceftaroline as monotherapy for persistent MRSAB were included. Most patients received at least 4 days of an appropriate anti-MRSA antimicrobial prior to ceftaroline and were able to clear bacteremia within 3 days. The most common rationales for ceftaroline use were progression of disease or nonresponse to current therapy. Higher off-label dosing of ceftaroline is often utilized to achieve optimal pharmacokinetic/pharmacodynamic parameters. Adverse events are not well described due to lack of follow-up; however, neutropenia has been associated with prolonged use.. Treatment options for persistent MRSAB remain few and far between. Ceftaroline is an effective agent for the salvage treatment of MRSAB. Off-label doses up to 600 mg every 8 hours are often used to achieve optimal pharmacokinetic/pharmacodynamic parameters. Because of lack of follow-up in these reports, the incidence of adverse effects of prolonged use of ceftaroline is not well defined.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Female; Humans; Methicillin-Resistant Staphylococcus aureus; Salvage Therapy; Staphylococcal Infections

We report a case of clearance of persistent bacteremia due to daptomycin non-susceptible, vancomycin-intermediate Staphylococcus aureus native mitral valve endocarditis with a combination of ceftaroline and daptomycin, in an 81-year-old medically complex patient who was not an operative candidate.

Topics: Aged, 80 and over; Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Humans; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Ceftaroline fosamil is a new subclass of cephalosporins with high intrinsic activity against various multi-resistant Gram-positive organisms, including Staphylococcus aureus and Streptococcus pneumoniae, as well as against Enterobacteriaceae causing bacteremia and infective endocarditis. Because of its pharmacokinetic profile and pharmacodynamic characteristics, this drug is a good therapeutic option for these infections. Experimental studies have shown good clinical efficacy for the treatment of endocarditis caused by S. aureus, regardless of their sensitivity to methicillin or vancomycin. Clinical experience is limited, although clinical trials and case series have reported a favorable clinical response in patients with bacteremia associated with skin and soft tissue infections, pneumonia, or infective endocarditis. Future studies should define more precisely the role of this new antibiotic in the treatment of these infections.

Topics: Animals; Bacteremia; Ceftaroline; Cephalosporins; Clinical Trials as Topic; Disease Models, Animal; Endocarditis, Bacterial; Humans; Staphylococcal Infections

Data regarding ceftaroline use for meticillin-resistant Staphylococcus aureus bacteraemia (MRSAB) are lacking. Here we review the outcomes of 31 patients with MRSAB treated with ceftaroline, including 9 patients with endocarditis. Clinical success was observed in 23 patients (74.2%). Adverse events associated with prolonged therapy were rare and included eosinophilic pneumonia, rash and diarrhoea. We conclude that ceftaroline can be used for MRSAB.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Staphylococcal Infections; Treatment Outcome; Young Adult

Few publications of prospective studies have described patient outcomes in community-acquired bacterial pneumonia (CABP)-associated bacteremia. Our objective, in performing this subgroup analysis, was to assess outcomes in subjects with CABP-associated bacteremia in 2 randomized, double-blind clinical studies comparing treatment with ceftaroline fosamil versus ceftriaxone.. Our analysis summarizes baseline subject demographics, distribution of baseline pathogens isolated from blood cultures, clinical response rates at Day 4, and clinical cure rates at end of therapy and test of cure (8 to 15 days after end of therapy) in subjects with bacteremic CABP in the ceFtarOline Community-acquired pneUmonia trial vS ceftriaxone in hospitalized patients (FOCUS) studies.. In the FOCUS studies, 23 of 614 patients in the ceftaroline fosamil-treated group and 22 of 614 patients in the ceftriaxone-treated group had CABP-associated bacteremia. Baseline demographics were similar between groups. Streptococcus pneumoniae was the most common baseline bloodstream isolate. For subjects with CABP-associated bacteremia, clinical response/cure rates were similar at Day 4 (60.9% vs 59.1%), end of therapy (69.6% vs 72.7%), and test of cure (69.6% vs 68.2%) for ceftaroline fosamil and ceftriaxone, respectively.. In subjects with CABP-associated bacteremia, ceftaroline fosamil demonstrated similar clinical outcomes at Day 4, end of therapy, and test of cure compared with ceftriaxone.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Ceftriaxone; Cephalosporins; Community-Acquired Infections; Double-Blind Method; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Treatment Outcome

Ceftaroline fosamil resulted in higher cure rates than ceftriaxone in patients with community-acquired bacterial pneumonia in 2 randomized trials (FOCUS 1 and FOCUS 2). The present analysis examines the subgroup of patients with Streptococcus pneumoniae infection to determine whether the apparent difference in cure rates persists after adjusting for potential covariates. We retrospectively pooled subjects with S. pneumoniae isolated at baseline in the original studies and employed logistic regression to evaluate the independent relationship between clinical cure and treatment with ceftaroline. Covariates evaluated included demographics, severity of illness, bacteremia, and pathogen characteristics. The final cohort included 139 subjects (69 ceftaroline, 70 ceftriaxone). Unadjusted cure rates were 85.5% and 68.6% (P = 0.009) in the ceftaroline and ceftriaxone groups, respectively. After logistic regression, ceftaroline remained associated with higher cure rates. Our findings indicate that ceftaroline may result in improved outcomes of S. pneumoniae pneumonia. Formal clinical trials are warranted to confirm this hypothesis.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Ceftriaxone; Cephalosporins; Community-Acquired Infections; Female; Humans; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Odds Ratio; Pneumonia, Pneumococcal; Retrospective Studies; Treatment Outcome

The preferred antibiotic salvage regimen for persistent methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) is unclear. We sought to evaluate the effectiveness and safety of vancomycin plus ceftaroline for persistent MRSAB. The primary outcome was time to MRSAB clearance post-ceftaroline initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day readmission for MRSAB, 90-day all-cause mortality, MRSAB-related mortality, and incidence of antibiotic-associated adverse effects.. Single-center, retrospective cohort study between January 1, 2016, and December 31, 2021.. State University of New York Upstate University Hospital, a 748-bed tertiary care, academic medical center in Syracuse, NY.. Adult patients were included if they had blood cultures positive for MRSA ≥72 h, received vancomycin monotherapy initially, and received vancomycin plus ceftaroline for ≥24 h. Patients were excluded if they received other anti-MRSA antibiotics, were pregnant, or were incarcerated. Of the 178 patients identified, 30 unique patients were evaluated.. Patients were medically complex with a median Pitt bacteremia score of 3, 63.3% (19/30) were admitted to the intensive care unit, and 66.7% (20/30) had infective endocarditis. Vancomycin-associated acute kidney injury was observed in 10% (3/30) of patients, which resulted in dose adjustments. No patients experienced ceftaroline-associated neutropenia or Clostridioides difficile infection, but 6.7% (2/30) developed a rash attributed to ceftaroline. Median time to MRSAB clearance post-ceftaroline initiation was 2.6 days. Microbiologic cure occurred in nearly all patients 96.7% (29/30). Median hospital length of stay was 19.5 days, and 6.7% (2/30) of patients had 90-day readmission for MRSAB. 90-day all-cause mortality and MRSAB-related mortality occurred in 26.7% (8/30) and 13.3% (4/30) of patients, respectively.. Vancomycin plus ceftaroline may represent an effective and well-tolerated salvage regimen option for persistent MRSAB.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Humans; Methicillin-Resistant Staphylococcus aureus; Retrospective Studies; Staphylococcal Infections; Vancomycin

This study aimed to evaluate both efficacy and safety of combination therapy with daptomycin plus ceftaroline (DAP/CPT) versus alternative therapy in the treatment of persistent methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB).. This retrospective, single-centre study investigated adult patients who underwent a change in antibiotic therapy for persistent MRSAB. Daptomycin plus ceftaroline was compared with alternative therapy after initial treatment with vancomycin or DAP monotherapy was modified. The primary outcome was in-hospital mortality, and several secondary efficacy and safety outcomes were evaluated.. A total of 68 patients with persistent MRSAB had initial therapy switched to DAP/CPT (n = 43) or alternative therapy (n = 25). In-hospital mortality was similar with DAP/CPT versus alternative therapy (16.3% vs. 16%; P = 1.0). On average, the total duration of bacteraemia was numerically 1 day less in patients switched to DAP/CPT (11.4 days vs. 12.5 days; P = 0.5). Daptomycin plus ceftaroline was de-escalated in 81% of patients after receiving combination therapy for an average of 12.5 days. Secondary outcomes, including rates of adverse events and emergence of antimicrobial resistance, were similar between the two groups.. Switching to DAP/CPT after approximately 1 week of persistent MRSA bacteraemia may result in similar clinical outcomes when compared with alternative therapy. Rates of adverse events and emergence of antimicrobial resistance were low without a statistically significant difference observed between DAP/CPT and alternative therapy. These findings, as well as the impact of earlier switch or prolonged treatment with the combination, require further investigation.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Daptomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus

Improvements in blood culture techniques and molecular-based diagnostics have led to increased recognition of Kingella kingae as an invasive human pathogen causing bacteremia, septic arthritis, osteomyelitis and endocarditis in young children. Serious disease and potentially life-threatening complications of infection due to K. kingae necessitate timely identification and appropriate antimicrobial therapy. Ceftaroline is a fifth-generation broad spectrum cephalosporin that possesses activity against Gram-negative and Gram-positive pathogens similar to third-generation cephalosporins, but also includes methicillin-resistant Staphylococcus aureus . This study reports the in vitro activity of ceftaroline and comparator agents against an international collection of K. kingae isolates.. A collection of 308 K. kingae isolates was obtained primarily from children with bacteremia, endocarditis, osteoarticular infections or from asymptomatic pediatric carriers. Isolates were tested for antibiotic susceptibility using Clinical and Laboratory Standard Institute broth microdilution methodology and screened for β-lactamase production using a nitrocefin chromogenic test.. Ceftaroline inhibited all K. kingae isolates at ≤0.06 mg/L (MIC 50/90 , 0.015/0.03 mg/L). Ceftaroline MICs were similar to results with ceftriaxone (MIC 50/90 , 0.015/0.015 mg/L), meropenem (MIC 50/90 , 0.015/0.015 mg/L) and ampicillin-sulbactam (MIC 50/90 , 0.06/0.06 mg/L). Ceftaroline MICs were slightly lower than MICs for cefuroxime and amoxicillin/clavulanate (MIC 50/90 , 0.06/0.12 mg/L). MICs were high for clindamycin (MIC 50/90 , 2/4 mg/L) and oxacillin (MIC 50/90 , 4/8 mg/L). Sixteen isolates (5.2%) yielded a positive nitrocefin test indicating production of β-lactamase; ceftaroline demonstrated equivalent MICs against β-lactamase - positive and β-lactamase - negative strains (MIC 50/90 , 0.015/0.3 mg/L).. The potent activity of ceftaroline against this large international collection of K. kingae isolates supports further clinical evaluation in children.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Ceftaroline; Cephalosporins; Child; Child, Preschool; Endocarditis; Humans; Kingella kingae; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests

The combination of daptomycin and ceftaroline used as salvage therapy is associated with higher survival and decreased clinical failure in complicated methicillin-resistant Staphylococcus aureus (MRSA) infections that are resistant to standard MRSA treatment. This study aimed to evaluate dosing regimens for coadministration of daptomycin and ceftaroline in special populations including paediatrics, renally impaired (RI), obese and geriatrics that generate sufficient coverage against daptomycin-resistant MRSA.. Physiologically based pharmacokinetic models were developed from pharmacokinetic studies of healthy adults, geriatric, paediatric, obese and RI patients. The predicted profiles were used to evaluate joint probability of target attainment (PTA), as well as tissue-to-plasma ratios.. The adult dosing regimens of 6 mg/kg every (q)24h or q48h daptomycin and 300-600 mg q12h ceftaroline fosamil by RI categories achieved ≥90% joint PTA when the minimum inhibitory concentrations in the combination are at or below 1 and 4 μg/mL against MRSA. In paediatrics, wherein there is no recommended daptomycin dosing regimen for S. aureus bacteraemia, ≥90% joint PTA is achieved when the minimum inhibitory concentrations in the combination are up to 0.5 and 2 μg/mL for standard paediatric dosing regimens of 7 mg/kg q24h daptomycin and 12 mg/kg q8h ceftaroline fosamil. Model predicted tissue-to-plasma ratios of 0.3 and 0.7 in the skin and lung, respectively, for ceftaroline and 0.8 in the skin for daptomycin.. Our work illustrates how physiologically based pharmacokinetic modelling can inform appropriate dosing of adult and paediatric patients and thereby enable prediction of target attainment in the patients during multitherapies.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Child; Daptomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus

Treatment of late-onset neonatal staphylococcal sepsis is sometimes challenging with feared side effects of vancomycin, increasing minimal inhibitory concentrations and questions about catheter management. In case of failure, ceftaroline was administered as a compassionate treatment in 16 infants (gestational age of less than 32 weeks and less than 28 postnatal days), whose first-line treatment failed. We report 11 successes and no severe adverse drug reactions. Larger data are required to confirm these encouraging results.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Humans; Infant; Infant, Newborn; Neonatal Sepsis; Sepsis; Staphylococcal Infections; Vancomycin

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Communicable Diseases; Daptomycin; Humans; Pharmacists; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus

Infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) are still associated with significant morbidity and mortality. Treatment failures of cefazolin (CFZ) have been reported and probably related to the inoculum effect. New treatments for severe MSSA infections are needed and ceftaroline fosamil (CPT) could be an option. Our aim was to describe the clinical characteristics of five patients with complicated MSSA bacteremia failing CFZ and successfully treated with CPT. We performed a retrospective chart review in a Hospital in Buenos Aires, Argentina; in a 12-month period, five patients (24%) of 21 with MSSA bacteremia experienced CFZ failure and were salvaged with CPT. The median time of CFZ therapy was 10 days before changing to CPT; four patients had evidence of metastatic spread and 2 had endocarditis. All patients experienced microbiological and clinical cure with CPT, which was used as monotherapy in 4 and in combination with daptomycin in another. One patient discontinued CPT due to neutropenia on day 23 of treatment. In patients with MSSA BSI failing current therapy, CPT could be a good therapeutic option.. Las infecciones causadas por Staphylococcus aureus sensible a la meticilina (SASM) todavía se asocian con una morbilidad y mortalidad significativas. Se han informado fallas en el tratamiento de cefazolina (CFZ) probablemente relacionadas con efecto inóculo. Nuevos tratamientos son necesarios para estas infecciones y ceftarolina fosamil (CPT) podría ser una opción. Nuestro objetivo fue describir las características clínicas de cinco pacientes con bacteriemia por SASM complicada con falla a CFZ y que fueron exitosamente tratados con CPT. Realizamos una revisión retrospectiva de historias clínicas en un hospital de Buenos Aires, Argentina; en un período de 12 meses, cinco pacientes (24%) de 21 con bacteriemia por SASM experimentaron falla a CFZ y fueron tratados con CPT. La mediana de tiempo de la terapia con CFZ fue de 10 días antes de cambiar a CPT; cuatro pacientes presentaban evidencia de diseminación metastásica y 2 tenían endocarditis. Todos los pacientes experimentaron curación microbiológica y clínica con CPT, que se utilizó como monoterapia en 4 y en combinación con daptomicina en otro. Un paciente interrumpió CPT debido a neutropenia el día 23 de tratamiento. En enfermos con infecciones graves por SASM que fallan en la terapia actual, CPT podría ser una buena opción terapéutica.

Topics: Anti-Bacterial Agents; Bacteremia; Cefazolin; Ceftaroline; Cephalosporins; Daptomycin; Humans; Methicillin; Retrospective Studies; Salvage Therapy; Staphylococcal Infections; Staphylococcus aureus

Complicated methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSIs), particularly those with delayed culture clearance, are associated with high mortality. Combination therapy with daptomycin and ceftaroline (DAP+CPT) represents a novel therapeutic approach to MRSA-BSI owing to synergistic bactericidal activity. This study aimed to compare DAP+CPT with historical standard of care (SoC) for treatment of complicated MRSA-BSI. This single-centre retrospective cohort study included patients with complicated MRSA-BSI at University of Colorado Hospital. Patients receiving DAP+CPT for ≥48 h between November 2013 and March 2020 or SoC with vancomycin or DAP ± gentamicin and/or rifampicin from November 2011 to December 2013 were compared. The primary outcome was clinical failure defined as a composite of MRSA-related mortality and recurrent infection at 60 days. A total of 60 patients received DAP+CPT (n = 30) or SoC (n = 30). Median age was 56 years and median Pitt bacteremia score was 3. Common infectious sites were endovascular (63%) and musculoskeletal (40%). DAP+CPT was associated with a numerically lower incidence of clinical failure compared with SoC (20% vs. 43%; P = 0.052). Multivariable analysis controlling for immunocompromised status (OR, 6.90, 95% CI 1.08-44.15), Charlson comorbidity index (OR, 1.12, 95% CI 0.90-1.39) and source control (OR, 0.35, 95% CI 0.08-1.46) associated DAP+CPT with 77% lower odds of clinical failure (OR, 0.23, 95% CI 0.06-0.89). In patients with complicated MRSA-BSI with delayed clearance, DAP+CPT trended towards lower rates of clinical failure than SoC and was significantly associated with decreased clinical failure after adjustment for baseline differences.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Drug Synergism; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Rifampin; Salvage Therapy; Standard of Care; Staphylococcal Infections; Treatment Outcome; Vancomycin

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Typing Techniques; Ceftaroline; Cephalosporins; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Genes, Bacterial; Humans; Linezolid; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Phylogeny; Rifampin; Staphylococcal Infections; Tetracycline; Turkey; Vancomycin; Vancomycin Resistance; Virginiamycin

Staphylococcus aureus is one of the major causes of bloodstream infections (BSI) worldwide, representing a major challenge for public health due to its resistance profile. Higher vancomycin minimum inhibitory concentrations (MIC) in S. aureus are associated with treatment failure and defining optimal empiric options for BSIs in settings where these isolates are prevalent is rather challenging. In silico pharmacodynamic models based on stochastic simulations (Monte Carlo) are important tools to estimate best antimicrobial regimens in different scenarios. We aimed to compare the pharmacodynamic profiles of different antimicrobials regimens for the treatment of S. aureus BSI in an environment with high vancomycin MIC.. Steady-state drug area under the curve ratio to MIC (AUC/MIC) or the percent time above MIC (fT > MIC) were modeled using a 5000-patient Monte Carlo simulation to achieve pharmacodynamic exposures against 110 consecutive S. aureus isolates associated with BSI.. Cumulative fractions of response (CFRs) against all S. aureus isolates were 98% for ceftaroline; 79% and 92% for daptomycin 6 mg/kg q24h and for the high dose of 10 mg/kg q24h, respectively; 77% for linezolid 600 mg q12h when MIC was read according to CLSI M100-S26 instructions, and 64% when MIC was considered at the total growth inhibition; 65% and 86% for teicoplanin, three loading doses of 400 mg q12 h followed by 400 mg q24 h and for teicoplanin 400 mg q12 h, respectively; 61% and 76% for vancomycin 1000 mg q12 h and q8 h, respectively.. Based on this model, ceftaroline and high-dose daptomycin regimens delivered best pharmacodynamic exposures against S. aureus BSIs. Teicoplanin higher dose regimen achieved the best CFR (86%) among glycopeptides, although optimal threshold was not achieved, and vancomycin performance was critically affected by the S. aureus vancomycin MIC ≥2 mg/L. Linezolid effectiveness (CFR of 73%) is also affected by high prevalence of isolates with linezolid MIC ≥2 mg/L. These data show the need to continually evaluate the pharmacodynamic profiles of antimicrobials for empiric treatment of these infections.

Topics: Anti-Bacterial Agents; Bacteremia; Brazil; Ceftaroline; Cephalosporins; Daptomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Monte Carlo Method; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

The use of daptomycin (DAP) in septic pulmonary emboli (SPE) remains controversial. We analyzed 29 cases of MRSA bacteremia complicated by SPE treated with DAP (n = 14) or DAP-ceftaroline fosamil (CPT; n = 15). Initial treatment with DAP monotherapy was found to have a success rate comparable with DAP-CPT (71% vs. 80%; p = 0.68).

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Cohort Studies; Daptomycin; Drug Therapy, Combination; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Staphylococcal Infections; Treatment Outcome

Topics: Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Humans; Methicillin; Methicillin-Resistant Staphylococcus aureus; Standard of Care; Staphylococcal Infections; Staphylococcus aureus

Topics: Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Humans; Methicillin; Methicillin-Resistant Staphylococcus aureus; Standard of Care

Topics: Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Humans; Methicillin; Methicillin-Resistant Staphylococcus aureus; Standard of Care; Staphylococcal Infections; Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) is a major cause of morbidity and mortality in hospitalized patients. Ceftaroline fosamil (CPT) is the only available beta-lactam antibiotic with in vitro and in vivo activities against MRSA. There is currently limited clinical experience with CPT in complicated MRSA BSI.. We report a series of eight patients, including three whose strains had reduced susceptibility to vancomycin.. CPT monotherapy was successfully used as salvage therapy for complicated MRSA BSI. The median time to documented clearance was 7 days.. Ceftaroline monotherapy is effective for clearance of refractory MRSA BSI related to implanted devices, endocarditis, and orthopedic infections.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; New Jersey; Salvage Therapy; Staphylococcal Infections; Treatment Failure

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Pneumonia, Bacterial; Pseudomonas; Staphylococcal Infections; Staphylococcus aureus

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Humans; Methicillin; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Salvage Therapy; Staphylococcal Infections

Novel therapies for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) are needed in the setting of reduced antibiotic susceptibilities and therapeutic failure. Ceftaroline is a cephalosporin antibiotic with MRSA activity. Although not FDA approved for MRSA BSI, ceftaroline has generated much interest as a potential treatment option. However, detailed descriptions of its use in this setting remain limited. To address this, we conducted a retrospective, multicenter, observational study of adult patients with MRSA BSI treated with at least 72 h of ceftaroline from 2011 to 2015. Safety outcomes were examined in the overall cohort, while efficacy outcomes were examined among patients who had not cleared their BSI prior to ceftaroline initiation. Data were also stratified by ceftaroline monotherapy or combination therapy. Predictors of clinical failure on ceftaroline treatment were also sought. Overall, 211 patients were included in the safety population; Clostridium difficile infection, rash, and neutropenia occurred in 6 patients (2.8%), 7 patients (3.3%), and 3 patients (1.4%), respectively. Clinical success was observed in 86 (68.3%) of the 126 patients included in the efficacy population. The monotherapy and combination therapy subgroups had similar proportions of patients experiencing success (69.7 and 64.9%, respectively). The median BSI durations post-ceftaroline treatment were 2 days (interquartile range, 1 to 4 days) for monotherapy and 3 days (interquartile range, 1.5 to 5 days) for combination therapy. Higher acute physiology and chronic health evaluation II scores and comorbid malignancy independently predicted treatment failure. Ceftaroline appears effective for MRSA BSI as both monotherapy and combination therapy. However, comparative studies are needed to further delineate the role of ceftaroline in MRSA BSI treatment.

Topics: Aged; Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Endocarditis; Female; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Staphylococcal Infections; Vancomycin

Although vancomycin has been the mainstay of therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections, its effectiveness has been challenged. Combination therapy may be used for patients with persistent MRSA bacteremia refractory to initial therapy. Studies have reported in vitro synergy between vancomycin and ceftaroline; however, clinical experience with this therapy is limited. Here, we report our experience with 5 cases of vancomycin-refractory MRSA bacteremia treated with the combination of vancomycin and ceftaroline.. Between January 2014 and August 2016, 5 patients were identified who received vancomycin and ceftaroline combination therapy due to persistent bacteremia or deterioration of their clinical status on vancomycin alone (despite a vancomycin MIC within the susceptible range).. Five patients presented with MRSA bacteremia secondary to endocarditis (n = 2), epidural abscess (n = 2), or left iliopsoas abscess (n = 1). Four of the 5 patients experienced microbiologic cure, and 1 patient transitioned to palliative care.. This case series serves to describe additional clinical experience with vancomycin and ceftaroline combination therapy. This combination may be considered when vancomycin monotherapy does not lead to microbiological and/or clinical improvement in patients with metastatic MRSA bacteremia. Additional studies are warranted to further define its role in salvage therapy for persistent MRSA bacteremia.

Topics: Abscess; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Salvage Therapy; Staphylococcal Infections; Vancomycin

Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia; however, its use has been subject to scrutiny due to failure in severe infections. Ceftaroline fosamil (CPT-F) is approved for MRSA acute bacterial skin and skin structure infections, but not for bloodstream infections. The clinical outcomes of treatment with CPT-F in patients with MRSA bacteremia were evaluated.. Patients diagnosed with MRSA bacteremia at Henry Ford Hospital in Detroit, Michigan, USA, involving isolates with a vancomycin minimum inhibitory concentration ≥1.0mg/l and susceptible in vitro to CPT-F, were systematically reviewed retrospectively. Ceftaroline fosamil-treated patients were matched with at least two vancomycin- and/or one daptomycin-treated control patient based on age-patients age 65 years or greater or less than 65 years of age. Outcomes evaluated included the duration of hospitalization, duration of therapy, adverse events, relapse, hospital readmission, and death.. Thirty consecutive cases of MRSA bacteremia treated with CPT-F during the period May 2011 to June 2013 were identified; these patients were matched to 56 MRSA bacteremia patients treated with vancomycin and 46 MRSA bacteremia patients treated with daptomycin. The primary source of MRSA bacteremia in the cohort treated with CPT-F was endocarditis (n=7, 23%), skin/wound (n=9, 30%), and bone/joint (n=8, 27%). The MRSA bacteremia in those treated with CPT-F was community-acquired in 43% of cases, healthcare-associated in 43%, and hospital-acquired in 13%. The mean length of hospital stay for these patients was 22 days. The overall 30-day mortality rate was 13% (n=4) in CPT-F patients versus 24% (n=11) in daptomycin patients and 11% (n=6) in vancomycin patients (p=0.188).. CPT-F demonstrated comparable clinical outcomes in MRSA bacteremia patients compared with the other agents, especially as salvage therapy.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Female; Hospitalization; Humans; Length of Stay; Male; Methicillin-Resistant Staphylococcus aureus; Michigan; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Salvage Therapy; Staphylococcal Infections; Treatment Outcome; Vancomycin

We determined the correlation between Etest and BMD MICs with bactericidal activity in MSSA blood isolates. Ceftriaxone was bactericidal in 36% and 9% of isolates exposed to the Etest and BMD MIC, respectively. With the sub-optimal activity of ceftriaxone, the Etest MIC may be a conservative method in identifying clinical utility.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Ceftaroline; Ceftriaxone; Cefuroxime; Cephalosporins; Cephalothin; Disk Diffusion Antimicrobial Tests; Humans; Oxacillin; Staphylococcus aureus

Among 8437 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from 143 medical centers in the United States (2012-2014), 7116 and 1321 were reported as community-acquired (CA) and hospital-acquired (HA) MRSA, respectively. CA-/HA-MRSA were most often isolated from patients with skin and skin structure infections (SSSI; 68.4/26.9%), pneumonia (13.7/49.0%) and bacteremia (10.0/17.7%). Overall, susceptibility rates were generally lower among HA-MRSA compared to CA-MRSA strains, especially for clindamycin (44.6 vs. 66.1%) and levofloxacin (21.4 vs. 35.5%). Also, susceptibility rates were lower for these two compounds among isolates from pneumonia compared to SSSI and bacteremia. Ceftaroline was broadly active against 98.0% of CA-MRSA and 94.3% of HA-MRSA (MIC50/90, 1μg/mL for both; no resistant isolate) overall, with little variation among infection type subsets.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Community-Acquired Infections; Cross Infection; Epidemiological Monitoring; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Pneumonia, Staphylococcal; Staphylococcal Infections; Staphylococcal Skin Infections; United States

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Staphylococcal Infections; Treatment Outcome; Vancomycin

To examine the activity of ceftaroline against reduced-vancomycin-susceptible MRSA isolates.. One-hundred and three MRSA blood culture isolates (predominantly ST239-MRSA-III), with varying vancomycin phenotypes, had their ceftaroline MICs determined by broth microdilution and MIC Evaluator strip (Oxoid-Thermo Fisher). Statistical analyses were performed that examined relationships with vancomycin and daptomycin MICs. Mutations in mecA were also examined.. All 103 isolates (including 60 heteroresistant vancomycin-intermediate Staphylococcus aureus/vancomycin-intermediate S. aureus) were susceptible to ceftaroline, with one isolate displaying heteroresistance that may be related to a mecA mutation. Higher ceftaroline MICs were associated with vancomycin-susceptible S. aureus isolates.. This study highlights that ceftaroline fosamil is an option for salvage therapy based on in vitro activity.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Drug Tolerance; Female; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Salvage Therapy; Staphylococcal Infections; Vancomycin

Pseudoaneurysms are vessel wall ruptures, that are often mistaken for deep vein thrombosis (DVT). A middle-aged man presented with right leg pain, swelling and erythema. His history was significant for persistent Staphylococcus aureus bacteraemia. Ultrasound revealed subacute DVT and laboratory parameters were suggestive of sepsis. He was started on intravenous heparin and antimicrobials. Owing to persistent anaemia despite blood transfusion, MRI of the right thigh was obtained. It revealed a 13×17 cm superficial femoral artery infected mycotic pseudoaneurysm (MPA) with a fresh haematoma. The patient underwent arterial ligation and extensive debridement. Intraoperative cultures revealed daptomycin-resistant vancomycin-intermediate S. aureus (VISA) and he was managed with 6 weeks of intravenous ceftaroline. MPAs are most common in the femoral artery and form <1% of aneurysms. Therapy involves surgical debridement and prolonged antimicrobials. VISA causing MPA is associated with worse outcomes. We report the first time use of ceftaroline in the management of a VISA MPA.

Topics: Aneurysm, False; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Debridement; Diagnosis, Differential; Drug Resistance, Microbial; Femoral Artery; Humans; Ligation; Male; Middle Aged; Mycoses; Staphylococcus aureus; Thigh; Vancomycin; Venous Thrombosis

Topics: Ampicillin; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Colony Count, Microbial; Drug Synergism; Enterococcus faecalis; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Microbial Viability

Coagulase negative Staphylococcus continues generating interest in critically ill patients, due to their infections in extended admissions, in instrumented patients and due to their described multidrug resistance, which include glycopeptide heterorresistance and the increase in oxazolidinone resistance. Ceftaroline is a new cephalosporin with activity against resistant gram-positives, which, being betalactam, may provide adequate safety profile in the critical ill patient. The aim of this study was to determine the activity of ceftaroline and other antimicrobial agents against methicillin and linezolid-resistant Staphylococcus epidermidis.. We studied susceptibility of ceftaroline, tigecycline, daptomycin and vancomycin in a total of sixty-eight methicillin and linezolid-resistant S. epidermidis isolates with clinical significance from an Intensive Care Unit, using E-test.. All strains were susceptible to the four antimicrobial agents, regardless of the level of resistance to linezolid.. Ceftaroline could be an alternative in the treatment of methicillin and linezolid-resistant S. epidermidis infections in critically ill patients.

Topics: Anti-Bacterial Agents; Bacteremia; Body Fluids; Catheter-Related Infections; Ceftaroline; Cephalosporins; Critical Care; Cross Infection; Daptomycin; Drug Resistance, Multiple, Bacterial; Exudates and Transudates; Humans; Linezolid; Methicillin; Minocycline; Staphylococcal Infections; Staphylococcus epidermidis; Tigecycline; Vancomycin

Topics: Administration, Intravenous; Aged; Bacteremia; Ceftaroline; Cephalosporins; Discitis; Drug Administration Schedule; Endocarditis; Humans; Kidney Failure, Chronic; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Renal Dialysis; Staphylococcal Infections

Guidelines recommend daptomycin combination therapy as an option for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia after vancomycin failure. Recent data suggest that combining daptomycin with a β-lactam may have unique benefits; however, there are very limited clinical data regarding the use of ceftaroline with daptomycin.. All 26 cases from the 10 medical centers in which ceftaroline plus daptomycin was used for treatment of documented refractory staphylococcal bacteremia from March 2011 to November 2012 were included. In vitro (synergy studies, binding assays, cathelicidin LL-37 killing assays), and in vivo (virulence assays using a murine subcutaneous infection model) studies examining the effects of ceftaroline with daptomycin were also performed.. Daptomycin plus ceftaroline was used in 26 cases of staphylococcal bacteremia (20 MRSA, 2 vancomycin-intermediate S aureus, 2 methicillin-susceptible S aureus [MSSA], 2 methicillin-resistant S epidermidis). Bacteremia persisted for a median of 10 days (range, 3-23 days) on previous antimicrobial therapy. After daptomycin plus ceftaroline was started, the median time to bacteremia clearance was 2 days (range, 1-6 days). In vitro studies showed ceftaroline synergy against MRSA and enhanced MRSA killing by cathelicidin LL-37 and neutrophils. Ceftaroline also induced daptomycin binding in MSSA and MRSA to a comparable degree as nafcillin. MRSA grown in subinhibitory concentrations of ceftaroline showed attenuated virulence in a murine subcutaneous infection model.. Ceftaroline plus daptomycin may be an option to hasten clearance of refractory staphylococcal bacteremia. Ceftaroline offers dual benefit via synergy with both daptomycin and sensitization to innate host defense peptide cathelicidin LL37, which could attenuate virulence of the pathogen.

Topics: Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacteremia; Cathelicidins; Ceftaroline; Cephalosporins; Daptomycin; Drug Therapy, Combination; Female; Humans; Male; Mice; Middle Aged; Salvage Therapy; Staphylococcal Infections; Staphylococcus

Elevated minimum inhibitory concentrations (MICs) of vancomycin against meticillin-resistant Staphylococcus aureus (MRSA) and the emergence of heteroresistant S. aureus strains have led to increased use of anti-MRSA antibiotics other than vancomycin. Ceftaroline fosamil is a novel cephalosporin with activity against MRSA, but there are limited clinical data on its use for MRSA bacteraemia (MRSAB) and against strains exhibiting high vancomycin MICs (2-4 μg/mL). This multicentre, retrospective, case-control study compared the microbiological and clinical effectiveness of ceftaroline used after vancomycin failure with that of vancomycin-treated controls for the treatment of MRSA with vancomycin MICs ≥ 2 μg/mL. In total, 32 patients were matched 1:1 with respect to vancomycin MIC, age and origin of bacteraemia. In the ceftaroline group, patients received prior MRSA therapy for a median of 5 days [interquartile range (IQR), 3-15.8 days] prior to switching to ceftaroline. Median time to eradication of MRSA was significantly less after treatment with ceftaroline compared with vancomycin [4 days (IQR, 3-7.5 days) vs. 8 days (IQR, 5.8-19.5 days); P=0.02]. Both clinical success at the end of treatment and recurrence of MRSA at Day 7 were trending towards being inferior in the vancomycin group, although the results did not attain statistical significance [81% vs. 44% (P=0.06) and 6% vs. 38% (P=0.08), respectively]. Ceftaroline added at the point of vancomycin failure resolves MRSAB more rapidly and with a higher rate of clinical success, therefore ceftaroline should be considered as an alternative for these difficult-to-treat infections.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Case-Control Studies; Ceftaroline; Cephalosporins; Demography; Disease Eradication; Female; Glycopeptides; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Staphylococcal Infections; Time Factors; Treatment Failure; Vancomycin

There are many limitations to the current antibiotics used for the treatment of severe methicillin-resistant Staphylococcus aureus (MRSA) infections. Ceftaroline is a new fifth-generation cephalosporin approved for the treatment of skin and soft tissue infections caused by MRSA and community-acquired pneumonia. We propose that ceftaroline can also be used successfully in more severe MRSA infections, including endocarditis. We conducted a retrospective chart review in a university-affiliated Department of Veterans Affairs hospital in San Diego, California (USA) of ten inpatients treated with ceftaroline for severe MRSA infection, including five cases of probable endocarditis (including two endocardial pacemaker infections), one case of pyomyositis with possible endocarditis, two cases of pneumonia (including one case of empyema), two cases of septic arthritis (including one case of prosthetic joint infection), and two cases of osteomyelitis. Seven of the 10 patients achieved microbiological cure. Six of the 10 patients achieved clinical cure. Seven patients were discharged from the hospital. Three patients were placed on comfort care and expired in the hospital; one achieved microbiological cure before death, and two remained bacteremic at time of death. In most patients, ceftaroline was effective for treatment of MRSA bacteremia and other severe MRSA infections. Adverse effects seen included rash, eosinophilia, pruritus, and Clostridium difficile infection. Ceftaroline can be a safe and effective drug for treatment of severe MRSA infections, and further comparative studies are warranted.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Arthritis, Infectious; Bacteremia; Ceftaroline; Cephalosporins; Endocarditis, Bacterial; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Osteomyelitis; Pneumonia, Staphylococcal; Prodrugs; Retrospective Studies; Staphylococcal Infections; Treatment Outcome

One of the newest methicillin-resistant Staphylococcus aureus (MRSA) antibiotics to receive FDA approval is ceftaroline fosamil, a member of a new subclass of cephalosporins with unique activity against MRSA. However, ceftaroline is currently only FDA approved for complicated skin/soft tissue infections and community-acquired pneumonia; there are currently no clinical data regarding its use in MRSA bacteraemia and endocarditis. We report a series of six patients in which ceftaroline was utilized as salvage monotherapy in persistent MRSA bacteraemia or endocarditis.. Using pharmacy records, 11 ceftaroline-treated patients were identified between January 2011 and November 2011 at University Health System and the South Texas Veterans Health Care System in San Antonio, TX, USA. All cases were reviewed and six patients received ceftaroline therapy for MRSA bacteraemia or endocarditis due to persistent or recurrent bacteraemia while on standard antibiotics (vancomycin or daptomycin).. All six patients experienced rapid clearance of their bacteraemia after starting ceftaroline. In the case of endocarditis for which the patient subsequently developed heart failure and required valve replacement, there was no evidence of growth from cultures taken from the excised valve, suggesting sterilization within 13 days of starting ceftaroline.. Ceftaroline exhibits potent anti-MRSA activity in both in vitro and animal studies, including rabbit endocarditis models; however, the lack of clinical data has limited its use in bacteraemia and endovascular infections in humans. We hope that this series serves as an initial stepping stone for further evaluation of this compound for more invasive infections due to MRSA.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Endocarditis, Bacterial; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Salvage Therapy; Staphylococcal Infections; Texas; Treatment Outcome

The activity of ceftaroline, a novel cephalosporin, was evaluated against 1337 isolates from patients with bacteraemic community-acquired pneumonia (CAP) requiring hospitalisation (including 119 Haemophilus influenzae, 9 Moraxella catarrhalis, 164 Staphylococcus aureus, 1007 Streptococcus pneumoniae and 38 Streptococcus pyogenes). Minimum inhibitory concentrations (MICs) were determined by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines, and susceptibility category assessments were made using CLSI or US Food and Drug Administration (FDA) breakpoints. Ceftaroline MICs were < or = 0.008-0.06 mg/L against H. influenzae, 0.25-2mg/L against methicillin-resistant S. aureus (MRSA), 0.06-1mg/L against methicillin-susceptible S. aureus, 0.015-0.5mg/L against M. catarrhalis and < or = 0.008-0.5mg/L against S. pneumoniae, and all S. pyogenes isolates had ceftaroline MICs < or = 0.008mg/L. Ceftaroline was more active than ceftriaxone or cefepime both against MRSA and penicillin-resistant pneumococci. More than 90% of MRSA isolates were resistant to clarithromycin and levofloxacin but were susceptible to linezolid or tigecycline. A high rate of clarithromycin resistance was also observed in the pneumococci. Ceftaroline was very active in vitro against all CAP isolates, including MRSA and penicillin-non-susceptible pneumococci, in contrast to the other beta-lactams tested. These data confirm ceftaroline as a new cephalosporin with enhanced anti-Gram-positive activity and suggest that ceftaroline has the potential to be a useful new agent in the treatment of CAP-associated bacteraemic infections.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Community-Acquired Infections; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Pneumonia, Bacterial