ppi-0903 and Osteomyelitis

Osteomyelitis is an infection involving bone.

Topics: Ceftaroline; Cephalosporins; Daptomycin; Drug Combinations; Female; Humans; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Osteomyelitis

We report a case of osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA) that is also non-susceptible to vancomycin, dalbavancin, ceftaroline, and ceftobiprole, in the absence of exposure to the latter three antibiotics. It was isolated from a patient with a 26-year history of cranial surgeries and episodes of osteomyelitis. Whole-genome sequencing was performed. It was found to belong to ST247 and the mecA gene was detected within the SSCmec type I (1B) gene cassette that lacked the E447K mutation known to produce resistance to ceftobiprole and ceftaroline. However, mutations in other genes related to resistance to these antibiotics were found.

Topics: Adult; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Drug Resistance, Multiple, Bacterial; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Teicoplanin; Vancomycin; Whole Genome Sequencing

Osteomyelitis is often challenging to treat. This analysis examined the clinical experience of patients with gram-positive osteomyelitis treated with ceftaroline fosamil in the phase 4 Clinical Assessment Program and Teflaro® Utilization Registry (CAPTURE) study.. Data including patient demographics, past illnesses, risk factors, disease characteristics, antibiotic use, pathogens isolated, and clinical outcome were collected between September 2013 and February 2015 by review of randomly ordered patient charts from participating sites in the United States. Clinical success was defined as discontinuation of ceftaroline fosamil following clinical cure with no further need for antibiotics or clinical improvement with switch to another antibiotic treatment.. A total of 150 patients with gram-positive osteomyelitis were treated with ceftaroline fosamil. Most patients (117/150; 78.0%) were treated with 600 mg ceftaroline fosamil per dose; 143/150 patients (95.3%) received a dose every 12 h. The majority (89/150 patients; 59.3%) had been previously diagnosed with diabetes mellitus or peripheral arterial disease. Osteomyelitis was associated with hardware in 32/150 patients (21.3%). Methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA; MSSA) were the most commonly isolated pathogens, observed in 93/150 (62.0%) and 21/150 (14.0%) patients, respectively. Clinical success with ceftaroline fosamil therapy was observed in 139/150 (92.7%) patients overall, 81/89 (91.0%) patients with diabetes or peripheral arterial disease, and 18/20 (90.0%) patients who had hardware implanted before ceftaroline fosamil therapy (none had hardware removed during therapy). Patients who received prior antibiotic therapy or ceftaroline fosamil as monotherapy experienced clinical success rates of 93.9% (107/114) and 91% (91/100), respectively. Among patients who received concurrent antibiotic therapy, the clinical success rate was 96.0% (48/50). Patients who were infected with MRSA or MSSA had clinical success rates of 92.5% (86/93) and 100% (21/21), respectively. A total of 2/150 (1.3%) patients discontinued ceftaroline fosamil therapy because of adverse events.. Clinical success rates with ceftaroline fosamil were high in patients with gram-positive osteomyelitis, including those with diabetes or peripheral arterial disease and those with MRSA or MSSA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Multicenter Studies as Topic; Osteomyelitis; Registries; Retrospective Studies; Risk Factors; Staphylococcal Infections; Staphylococcus aureus; Young Adult

Despite limited clinical data, ceftaroline is commonly used for treatment of complicated, invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). A retrospective chart review was conducted of adult patients receiving ceftaroline for MRSA osteomyelitis admitted between April 2011 and March 2016 at a five-hospital system. Twelve patients met the inclusion criteria. All patients received prior antimicrobial therapy with a median time to switch to ceftaroline of 45.5 days. Five of the 12 patients (41.7%) met criteria for ceftaroline failure. Patients with vertebral osteomyelitis (58%) had a longer length of stay, longer ceftaroline treatment, but similar success rates to those with non-vertebral osteomyelitis (57% vs. 60%). Ceftaroline is a viable alternative for a challenging patient population that has failed or are unable to receive other therapies.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Drug Resistance, Microbial; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Osteomyelitis; Prognosis; Retrospective Studies; Staphylococcal Infections; United States

Infections of the spine lead to considerable morbidity and a high cost to the global healthcare system. Currently, evidence for using ceftaroline, an advanced-generation cephalosporin active against methicillin-resistant Staphylococcus aureus (MRSA), in spine infections is limited.. Describing Infections of the Spine treated with Ceftaroline (DISC) is a multicentre, retrospective, cohort study that evaluated ceftaroline for treating spine infections. Patients were included if they were aged ≥18 years, diagnosed with a spine infection and treated with ceftaroline for ≥28 days. A control group was identified with the same inclusion criteria as the study population except they were treated with a comparator antibiotic for ≥28 days.. Thirty-seven patients were included each in the ceftaroline and control groups. MRSA was the most commonly identified pathogen. With no differences between groups in age, sex, race or co-morbidities (with the exception of chronic kidney disease), treatment with ceftaroline led to similar clinical success compared with the control group. Multivariate regression analysis did not show a significant difference between the two groups in terms of clinical success after controlling for other covariates (adjusted odds ratio=1.49; P=0.711). More patients who received ceftaroline were discharged to an extended-care or rehabilitation facility than home compared with controls (81% vs. 54%, respectively; P=0.024). Side effects and toxicities were rare, including one case of eosinophilic pneumonia in the ceftaroline group.. Ceftaroline appears to be a safe and effective therapy for infections of the spine, including from MRSA.

Topics: Adult; Aged; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Female; Humans; Male; Middle Aged; Osteomyelitis; Retrospective Studies; Spinal Diseases; Staphylococcal Infections

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

To evaluate the activity of a new cephalosporin, ceftaroline, in comparison with other antistaphylococcal drugs (linezolid and vancomycin) at projected human therapeutic doses against methicillin-resistant Staphylococcus aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) strains.. Using a rabbit experimental model of acute osteomyelitis, efficacy was assessed following 4 days of treatment by colony counts of infected bone tissues (joint fluid, femoral bone marrow and bone).. Although vancomycin remains the standard treatment for MRSA osteomyelitis, it was ineffective against the MRSA strain and poorly active against GISA infections in this model. Ceftaroline and linezolid demonstrated significant activity in bone marrow and bone, and were significantly better than vancomycin treatment. However, ceftaroline was the only drug to exhibit significant activity against MRSA in infected joint fluid.. The present study supports ceftaroline as a promising therapeutic option for the treatment of severe MRSA infections, including osteomyelitis.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Bone and Bones; Bone Marrow; Ceftaroline; Cephalosporins; Disease Models, Animal; Female; Linezolid; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Oxazolidinones; Rabbits; Staphylococcal Infections; Treatment Outcome; Vancomycin