ppi-0903 and Endocarditis--Bacterial

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

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

Ceftaroline is a fifth-generation cephalosporin and represents an alternative in the treatment of infective endocarditis (IE). The main objective of this study was to describe the incidence of in-hospital and 42-day mortality in patients with IE treated with ceftaroline.. An observational retrospective study included adult patients with IE admitted during a 3.5-year period (January 2018-June 2021) and treated with ceftaroline in a single center. All cases were definite or possible IE according to the modified Duke criteria.. Seventy cases were analyzed. The mean age was 67.35 ± 16.62 (16-89) and 39 (55.7%) were males. The mean number of days of treatment with ceftaroline was 21.26 ± 16.17 (1-75). Overall mortality at 42 days was 30%, 20.7% in the first line, and 36.6% in rescue therapy. Predictors of 42 days-mortality were increased Charlson comorbidity index (CCI) (OR of 1.7 per 1 point increment, 95% CI 1.2-2.4, P 0.001), presence of methicillin-resistance (OR 6.8, 95% CI 1.3-36.8, P 0.026) and evidence of septic shock (OR 8.6 95% CI 1.7-44.2, P 0.01). Predictors of 42 days of therapeutic failure were the increase in the CCI (OR of 1.6 per 1 point increment, 95% CI 1.3-2.1, P 0.000) and septic shock (OR 4.5 95% CI 1.1-18 P 0.036). Adverse effects were described in 6/70 (8.6%) of the patients, precipitating in 4/70 (5.7%) the definitive withdrawal of the antibiotic.. The incidence of in-hospital and 42 day-mortality of IE patients treated with ceftaroline remains similar to literature data. Increased CCI, septic shock, and methicillin resistance are associated with poor prognosis.

Topics: Adult; Aged; Aged, 80 and over; Ceftaroline; Cephalosporins; Endocarditis; Endocarditis, Bacterial; Female; Hospital Mortality; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Shock, Septic

The combination of daptomycin (DAP) plus ampicillin (AMP), ertapenem (ERT), or ceftaroline has been demonstrated to be efficacious against a DAP-tolerant Enterococcus faecium strain (HOU503). However, the mechanism for the efficacy of these combinations against DAP-resistant (DAP-R) E. faecium strains is unknown.. We investigated the efficacy of DAP in combination with AMP, ERT, ceftaroline, ceftriaxone, or amoxicillin against DAP-R E. faecium R497 using established in vitro and in vivo models. We evaluated pbp expression, levels of penicillin-binding protein (PBP) 5 (PBP5) and β-lactam binding affinity in HOU503 versus R497.. DAP plus AMP was the only efficacious regimen against DAP-R R497 and prevented emergence of resistance. DAP at 8, 6, and 4 mg/kg in combination with AMP was efficacious but showed delayed killing compared with 10 mg/kg. PBP5 of HOU503 exhibited amino acid substitutions in the penicillin-binding domain relative to R497. No difference in pbp mRNA or PBP5 levels was detected between HOU503 and R497. labeling of PBPs with Bocillin FL, a fluorescent penicillin derivative, showed increased β-lactam binding affinity of PBP5 of HOU503 compared with that of R497.. Only DAP (10 mg/kg) plus AMP or amoxicillin was efficacious against a DAP-R E. faecium strain, and pbp5 alleles may be important contributors to efficacy of DAP plus β-lactam therapy.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; beta-Lactams; Ceftaroline; Cephalosporins; Daptomycin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecium; Ertapenem; Gram-Positive Bacterial Infections; Microbial Sensitivity Tests; Rats; Sequence Alignment; Transcriptome

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Endocarditis, Bacterial; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests

The clinical experience of ceftaroline fosamil (CPT-F) therapy for Gram-positive infective endocarditis is reported from CAPTURE, a retrospective study conducted in the USA.. Data, including patient demographics, medical history, risk factors, microbiological aetiology and clinical outcomes, were collected by review of patient charts between September 2013 and February 2015.. Patients (n=55) with Gram-positive endocarditis were treated with CPT-F. The most common risk factors were intravascular devices (43.6%), diabetes mellitus (40.0%) and injection drug use (38.2%). The most commonly isolated pathogens were meticillin-resistant Staphylococcus aureus (MRSA; 80%), meticillin-susceptible S. aureus (MSSA; 7.3%) and coagulase-negative staphylococci (7.3%). CPT-F was given as first-line therapy in 7.3% of patients and as second-line or later therapy in 92.7% of patients, and as monotherapy in 41.8% of patients and as concurrent therapy in 58.2% of patients. Clinical success was observed in 82.6% (19/23) of patients treated with CPT-F as monotherapy. In patients treated with CPT-F as first-line therapy or second-line or later therapy, 75.0% (3/4) and 70.6% (36/51) achieved success, respectively. Clinical success was observed in 77.3% (34/44) of patients with MRSA and 25% (1/4) of patients with MSSA. Two patients discontinued treatment with CPT-F due to an adverse event.. CPT-F treatment was associated with a high rate of clinical success in patients with Gram-positive infective endocarditis, including those with risk factors and infections caused by MRSA. A high rate of clinical success was observed in patients treated with CPT-F used as first- line therapy or second-line or later therapy, or as monotherapy or in combination with other antibiotics.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Endocarditis, Bacterial; Female; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United States; Young Adult

Enterococci frequently cause severe biofilm-associated infections such as endocarditis. The combination of ampicillin/ceftriaxone has recently been clinically evaluated as non-inferior compared with the standard therapy of ampicillin/gentamicin for treatment of Enterococcus faecalis endocarditis. Ceftaroline is a novel cephalosporin with enhanced activity against Gram-positive bacteria.. To compare the in vitro effectiveness of the ceftaroline/ampicillin combination with those of gentamicin/ampicillin and ceftriaxone/ampicillin in planktonic and biofilm cultures of clinical E. faecalis isolates.. Synergistic effects at the planktonic level were analysed by chequerboard assays in 20 E. faecalis isolates. Biofilm-eradicating and biofilm-preventing activities of the antibiotics and their combinations were determined by confocal laser scanning microscopy with quantification by quantitative biofilm analysis (qBA) algorithm and cfu/mL determination.. Comparable synergistic effects were observed for both β-lactam combinations in most isolates, in contrast to gentamicin/ampicillin. However, none of the antibiotic combinations succeeded in eradicating mature biofilms. Gentamicin showed promising biofilm-preventing activity, but at concentrations above those clinically tolerable. The β-lactams showed a U-shape dose-response relationship in biofilm prevention. Only exposure to cephalosporins caused alterations in cell morphology, which resulted in cell elongation and reclustering in a concentration-dependent manner. Reclustering was associated with high occurrences of small colony variants (SCVs), especially at high ceftriaxone concentrations.. This study suggests that combinations of cephalosporins or gentamicin with ampicillin may be advantageous only while bacteraemia persists, whereas combinations have no advantage over monotherapy regarding the treatment of mature biofilms. The selection of SCVs at high ceftriaxone concentrations is worth further study.

Topics: Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Biofilms; Ceftaroline; Ceftriaxone; Cephalosporins; Cohort Studies; Drug Synergism; Endocarditis, Bacterial; Enterococcus faecalis; Female; Gentamicins; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Echocardiography, Transesophageal; Endocarditis, Bacterial; Heart Ventricles; Humans; Immunocompetence; Magnetic Resonance Imaging; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Staphylococcal Infections; Stroke Volume; Treatment Refusal

We report a case of infective endocarditis (IE) caused by ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant

Topics: Adult; Amino Acid Substitution; Anti-Bacterial Agents; Bacterial Proteins; Ceftaroline; Cephalosporins; Cross Infection; Daptomycin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Endocarditis, Bacterial; Gene Expression; Humans; Male; Methicillin; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Penicillin-Binding Proteins; Staphylococcal Infections; Vancomycin

Right-sided infective endocarditis (RIE) is commonly due to Staphylococcus aureus and often involves the tricuspid valve (TV). A 31-year-old man with prior intravenous drug use presented with substernal pain, cough, dyspnoea and fever. Examination revealed a febrile, tachycardic male with peripheral infective endocarditis stigmata and right-heart failure. Laboratory parameters demonstrated leucocytosis, lactic acidosis and methicillin-resistant S. aureus (MRSA) bacteraemia. Echocardiography demonstrated multiple TV echodensities and chest imaging confirmed septic emboli. The MRSA species demonstrated 'vancomycin-creep', necessitating therapy with daptomycin and ceftaroline. Owing to persistent bacteraemia and septic shock, the patient underwent TV surgery, but continued to have a poor postoperative course with subsequent death. Indications for surgical therapy of RIE are limited to the European guidelines and most data are extrapolated from left-heart disease. MRSA exhibiting vancomycin-creep portends a poorer prognosis and requires aggressive therapy. We advocate the use of ceftaroline salvage therapy with daptomycin, pending further trials.

Topics: Adult; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Daptomycin; Drug Resistance, Multiple, Bacterial; Endocarditis, Bacterial; Fatal Outcome; Heart Valve Diseases; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Mitral Valve; Staphylococcal Infections; Tricuspid Valve; Vancomycin

Infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin and daptomycin has few adequate therapeutic options. Ceftaroline (CPT) is bactericidal against daptomycin (DAP)-nonsusceptible (DNS) and vancomycin-intermediate MRSA, but supporting data are limited for IE. This study evaluated the activities of ceftaroline, vancomycin, daptomycin, and the combination of ceftaroline plus daptomycin against DNS MRSA in a pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial vegetations (SEVs). Simulations of ceftaroline-fosamil (600 mg) every 8 h (q8h) (maximum concentration of drug in serum [Cmax], 21.3 mg/liter; half-life [t1/2], 2.66 h), daptomycin (10 mg/kg of body weight/day) (Cmax, 129.7 mg/liter; t1/2, 8 h), vancomycin (1 g) q8h (minimum concentration of drug in serum [Cmin], 20 mg/liter; t1/2, 5 h), and ceftaroline plus daptomycin were evaluated against 3 clinical DNS, vancomycin-intermediate MRSA in a two-compartment, in vitro, PK/PD SEV model over 96 h with a starting inoculum of ∼8 log10 CFU/g. Bactericidal activity was defined as a ≥ 3-log10 CFU/g reduction from the starting inoculum. Therapeutic enhancement of combinations was defined as ≥ 2-log10 CFU/g reduction over the most active agent alone. MIC values for daptomycin, vancomycin, and ceftaroline were 4 mg/liter, 4 to 8 mg/liter, and 0.5 to 1 mg/liter, respectively, for all strains. At simulated exposures, vancomycin was bacteriostatic, but daptomycin and ceftaroline were bactericidal. By 96 h, ceftaroline monotherapy offered significantly improved killing compared to other agents against one strain. The combination of DAP plus CPT demonstrated therapeutic enhancement, resulting in significantly improved killing versus either agent alone against 2/3 (67%) strains. CPT demonstrated bactericidal activity against DNS, vancomycin-intermediate MRSA at high bacterial densities. Ceftaroline plus daptomycin may offer more rapid and sustained activity against some MRSA in the setting of high-inoculum infections like IE and should also be considered.

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Colony Count, Microbial; Computer Simulation; Daptomycin; Drug Combinations; Endocarditis, Bacterial; Half-Life; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Vancomycin

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Endocarditis, Bacterial; Female; Humans; Male; Methicillin Resistance; Middle Aged; Salvage Therapy; Staphylococcal Infections; Staphylococcus; Treatment Outcome

The case is described of a frail patient who developed prosthetic valve endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA). Conventional antimicrobial treatments either failed or were contraindicated, and the patient was judged unsuitable for a further valve replacement. A salvage therapy with high doses of a new cephalosporin, ceftaroline, given three times daily was undertaken; subsequently, the patient had not relapsed at two months after completing a six-week course of ceftaroline. Ceftaroline deserves major attention as an alternative choice in difficult-to-treat MRSA endocarditis.

Topics: Aged; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Endocarditis, Bacterial; Frail Elderly; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Prosthesis-Related Infections; Staphylococcal Infections; Treatment Outcome

A recurrent case of left-sided endocarditis caused by high-level aminoglycoside-resistant Enterococcus faecalis was successfully treated with ceftaroline and daptomycin. This combination demonstrated excellent synergy in vitro. Mechanistically, ceftaroline enhanced binding of daptomycin to the cell membrane and sensitized E. faecalis to killing by human cathelicidin LL-37, a cationic innate host defense peptide. Daptomycin plus ceftaroline may be considered in salvage therapy in E. faecalis endovascular infections and requires further study.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cathelicidins; Ceftaroline; Cell Membrane; Cephalosporins; Daptomycin; Drug Resistance, Bacterial; Drug Synergism; Endocarditis, Bacterial; Enterococcus faecalis; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged

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

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Daptomycin; Debridement; Drug Resistance, Bacterial; Endocarditis, Bacterial; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Osteomyelitis; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

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 aim of this study was to compare the in vivo activities of the new antistaphylococcal drugs ceftaroline fosamil, daptomycin and tigecycline at projected human therapeutic doses against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) strains in a rabbit model of endocarditis.. The efficacy of therapeutic regimens in our model was evaluated following 4 days of treatment by determining colony counts of infected vegetations. Emergence of resistant variants during therapy was assessed.. Using this model of infective endocarditis, ceftaroline fosamil and daptomycin demonstrated high bactericidal in vivo activity (reduction of >5 log(10) cfu/g of vegetation) after a 4 day treatment against MSSA, MRSA and GISA strains. Both drugs were more efficacious than tigecycline, which showed moderate activity but failed to exhibit a bactericidal effect. Ceftaroline was superior to daptomycin in terms of sterilization of the vegetations. Emergence of resistant variants during daptomycin therapy was observed in two animals (one in the MSSA group and one in the MRSA group) but was not observed in ceftaroline- or tigecycline-treated animals.. The novel β-lactam agent ceftaroline fosamil was the most active bactericidal drug in this model and is a promising therapeutic option for the treatment of severe S. aureus infections, including those caused by MRSA and GISA strains.

Topics: Animals; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Colony Count, Microbial; Daptomycin; Disease Models, Animal; Drug Resistance, Bacterial; Endocarditis, Bacterial; Female; Methicillin-Resistant Staphylococcus aureus; Microbial Viability; Minocycline; Rabbits; Rodent Diseases; Staphylococcal Infections; Tigecycline; Treatment Outcome

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Ceftaroline; Cephalosporins; Disease Models, Animal; Endocarditis, Bacterial; Endocardium; Female; Injections, Intramuscular; Methicillin-Resistant Staphylococcus aureus; Rabbits; Staphylococcal Infections; Treatment Outcome

We assessed the in vitro and in vivo efficacy of the novel parenteral broad-spectrum cephalosporin ceftaroline against Enterococcus faecalis in time-kill experiments and in a rabbit endocarditis model with simulated human dosing. Ceftaroline was more active than either vancomycin or linezolid against vancomycin-sensitive and -resistant isolates of E. faecalis.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Endocarditis, Bacterial; Enterococcus faecalis; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Oxazolidinones; Rabbits; Vancomycin; Vancomycin Resistance

Using the rabbit endocarditis model, we compared the activity of a new broad-spectrum cephalosporin, ceftaroline, with those of linezolid and vancomycin against methicillin-resistant Staphylococcus aureus. After a 4-day treatment, ceftaroline exhibited superior bactericidal in vivo activity against resistant S. aureus strains and appeared to be the most effective drug against a heterogeneous glycopeptide-intermediate S. aureus strain.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Area Under Curve; Ceftaroline; Cephalosporins; Chromatography, High Pressure Liquid; Colony Count, Microbial; Endocarditis, Bacterial; Immunoenzyme Techniques; Linezolid; Methicillin Resistance; Microbial Sensitivity Tests; Oxazolidinones; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin; Vancomycin Resistance