Ceftaroline as salvage therapy for methicillin susceptible staphylococcus aureus complicated bacteremia / Ceftarolina como tratamiento de rescate para la bacteriemia complicada por Staphylococcus aureus sensible a la meticilina

Abstract 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 com plicated 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.

Resumen 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 experimen taron 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.

Eficacia y seguridad de ceftarolina fosamil en niños: revisión sistemática y metaanálisis / Safety and effectiveness of ceftaroline fosamil in children: a systematic review and meta-analysis

Introducción. La resistencia a los antibióticos plantea un problema de salud mundial cada vez mayor, por lo que la búsqueda de nuevos y más efectivos antibióticos es prioritaria. La ceftarolina tiene un amplio espectro de actividad contra cepas Gram-positivas clínicamente relevantes, que incluyen el Staphylococcus aureus meticilino resistente y cepas de Streptococcus pneumoniae resistentes, así como algunos patógenos Gram-negativos implicados en infecciones de piel y tejidos blandos o en la neumonía adquirida en la comunidad; es una potencial opción terapéutica. Se realizó una revisión sistemática que evaluó si la ceftarolina era más efectiva y segura que los comparadores. Material y métodos. Se realizó una búsqueda bibliográfica exhaustiva para identificar estudios clínicos experimentales que compararan la seguridad y eficacia de la ceftarolina con un comparador en la población pediátrica. El criterio de evaluación de eficacia fue la tasa de fracaso terapéutico y, para seguridad, la presencia de cualquier efecto adverso. Resultados. Se identificaron tres estudios, 2 de neumonía adquirida en la comunidad y uno de infecciones de piel y tejidos blandos. En ninguno, se detectó diferencia en el riesgo de fracaso terapéutico, RR 0,97 (0,54-1,73), ni en el criterio de seguridad, RR 0,79 (0,51-1,23). Conclusiones. La evidencia disponible sugiere que la ceftarolina podría ser una opción terapéutica válida en el tratamiento de las infecciones de piel y tejidos blandos o neumonía adquirida en la comunidad en pacientes pediátricos. No se encontraron trabajos de alta calidad de evidencia en otro tipo de infecciones o en pacientes admitidos en la Unidad de Cuidados Críticos.

Introduction. Antibiotic resistance is an increasingly growing health problem worldwide, so it is imperative to look for new, more effective antibiotics. Ceftaroline has a broad spectrum of activity against clinically relevant Grampositive strains, including methicillin-resistant Staphylococcus aureus and resistant Streptococcus pneumoniae strains, as well as Gram-negative pathogens implicated in skin and soft tissue infections or community-acquired pneumonia; it is therefore a potential therapeutic option. We conducted a systematic review to assess whether ceftaroline was safer and more effective than comparators. Material and methods. A comprehensive bibliographic search was done to identify experimental clinical trials that compared the safety and effectiveness of ceftaroline to a comparator in the pediatric population. The rate of therapeutic failure was used to determine the effectiveness, while the presence of any adverse event was considered for safety. Results. Three studies were identified: two in community-acquired pneumonia and one in skin and soft tissue infections. No study showed a difference in the risk for therapeutic failure, relative risk (RR): 0.97 (0.54-1.73), or safety criterion, RR: 0.79 (0.51-1.23). Conclusions. The available evidence suggests that ceftaroline may be a valid therapeutic option for the management of skin and soft tissue infections or community-acquired pneumonia in pediatric patients. No studies with a high-quality of evidence were observed in other types of infections or in patients admitted to the critical care unit.

Ceftaroline resistance in Staphylococcus pseudintermedius gene mecA carriers / Resistência à ceftarolina em Staphylococcus pseudintermedius portadores do gene mecA

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) being a constant concern, ceftaroline fosamil has been recently approved as a new cephalosporin, active against MRSA, for use in humans; only rare cases of resistance have been reported till date. There is no report of resistance to ceftaroline in Staphylococcus pseudintermedius, which is the main bacterium causing dermatitis and otitis in dogs. To evaluate staphylococcal resistance to ceftaroline, 35 isolates of methicillin-resistant S. pseudintermedius (MRSP), carrying the mecA gene, from 26 dogs with folliculitis and nine dogs with external otitis, underwent disk diffusion test with cefoxitin, oxacillin, and ceftaroline. Tests with cefoxitin and oxacillin showed > 90% sensitivity in methicillin resistance detection. In the disk diffusion test, 97.14% (34/35) were resistant to cefoxitin, 94.29% (33/35) to oxacillin, and 31.43% (11/35) to ceftaroline. Of the ceftaroline-resistant strains, 27.27% (3/11) were obtained from the ears of dogs while the rest (8/11) were from the skin. The current report is the first description of MRSP resistance to ceftaroline.(AU)

Infecções causadas por Staphylococcus aureus resistente à meticilina (MRSA) são uma preocupação médica constante. A ceftarolina fosamila é uma nova cefalosporina ativa contra Staphylococcus aureus resistente à meticilina recentemente aprovada para uso em humanos e raros casos de resistência relatados até agora. Não há relatos de resistência à ceftarolina em Staphylococcus pseudintermedius, principal bactéria causadora de dermatite e otite em cães. Com o objetivo de avaliar a resistência estafilocócica à ceftarolina, 35 amostras de S. pseudintermedius resistentes à meticilina (MRSP), portadoras do gene mecA, provenientes de 26 cães com foliculite e 9 com otite externa foram submetidos ao teste de disco-difusão com cefoxitina, oxacilina e ceftarolina. Os testes realizados com cefoxitina e oxacilina mostraram mais de 90% de sensibilidade na detecção da resistência à meticilina em ambas. No teste da disco-difusão, 97,14% (1/35) foram resistentes à cefoxitina, 94,29% (3/35) à oxacilina e 31,43% (11/35) à ceftarolina. Das cepas resistentes às ceftarolina, 27,27 (3/11) foram provenientes de ouvido de cães e as demais (8/11), provenientes da pele, sendo essa primeira descrição de resistência de MRSP à ceftarolina na literatura atual.(AU)

Nuevas cefalosporinas / New cephalosporins

Resumen La resistencia bacteriana se ha incrementado en América Latina y el mundo, por lo que se requiere investigación y creación de nuevos antimicrobianos capaces de erradicar a los microorganismos resistentes. Se realizó una revisión acerca de nuevas cefalosporinas y sus combinaciones con un inhibidor de β-lactamasas, recopilando información de espectro, farmacocinética, farmacodinamia y estudios clínicos de las indicaciones actuales para ceftarolina, ceftazidima/avibactam y ceftolozano/tazobactam. La primera, con actividad frente a Staphylococcus aureus y Staphylococcus coagulasa negativa sensibles y resistentes a meticilina, y contra Streptococcus pneumoniae resistente a penicilina; por lo tanto, aprobada para uso en neumonía bacteriana adquirida en comunidad e infecciones bacterianas de piel y tejidos blandos. Entre las nuevas combinaciones, ceftazidima, una cefalosporina de tercera generación con actividad anti-pseudomonas, asociada a avibactam, un inhibidor de β-lactamasas, ha demostrado efectividad en el tratamiento de infecciones abdominales e infecciones urinarias complicadas. Por último, la combinación ceftolozano y el conocido tazobactam presenta acción comparable a la combinación de ceftazidima y avibactam por su actividad contra bacilos gramnegativos y, en combinación con metronidazol no presenta inferioridad a meropenem en infecciones intra-abdominales. Se presentan los estudios clínicos y las potenciales indicaciones y escenarios de uso de estas cefalosporinas.

Bacterial resistance has increased in Latin America and the world, making research and creation of new antimicrobials capable of eradicating resistant microorganisms essential. A review of new cephalosporins and their combinations with a beta-lactamase inhibitor was conducted, collecting data on the spectrum, pharmacokinetic and pharmacodynamic profile and clinical studies of the current indications for ceftaroline, and the combinations ceftazidime with avibactam and ceftolozane with tazobactam. The first one has activity against methicillin-resistant Staphylococcus aureus and coagulase negative Staphylococcus (SCoN) and against penicillin-resistant Streptococcus pneumoniae, therefore approved for use in community-acquired pneumonia and acute bacterial skin and skin structure infections. Among the new combinations, ceftazidime, a third generation cephalosporin with antipseudomonal activity, associated with avibactam, a betalactamase inhibitor, has been shown to be effective in the treatment of abdominal infections and complicated urinary infections. Finally, the combination of ceftolozane with tazobactam has comparable action to ceftazidime with avibactam due to its activity against Gram negative rods, and in combination with metronidazole they do not present inferiority to meropenem in intra-abdominal infections. The clinical studies are presented, as well as the potential indications and clinical scenarios for their use of this cephalosporins.

In vitro activity of ceftaroline: A novel antibiotic against methicillin‑resistant Staphylococcus aureus.

Introduction: Staphylococcus is one of the most common causes of nosocomial infection, especially pneumonia, surgical site infections, blood stream infections, and continues to be a major cause of community‑acquired infections. The emergence of penicillin resistance followed by the development and spread of strains resistant to the semisynthetic penicillins such as methicillin, oxacillin and nafcillin, macrolides, tetracycline, and aminoglycosides has made the treatment of staphylococcal infection a global challenge. To treat this multidrug‑resistant methicillin‑resistant Staphylococcus aureus (MRSA), the only option available is glycopeptides such as vancomycin. However, recently, vancomycin‑intermediate S. aureus and vancomycin‑resistant S. aureus strains have emerged with different resistance mechanism. There are newer drugs in the pipeline against MRSA such as ceftaroline, dalbavancin, oritavancin, and tedizolid; however, very little data are available for their use. Recently, ceftaroline has been approved by the US Food and Drug Administration for the treatment of acute bacterial skin and soft tissue infections and community‑acquired bacterial pneumonia due to MRSA. Hence, we tried to evaluate in vitro activity of ceftaroline against MRSA. Aim: The aim of this study was to detect in vitro activity of new cephalosporin, ceftaroline, against MRSA. Materials and Methods: Thirty nonduplicate MRSA strains were collected from various clinical samples, and minimum inhibitory concentration (MIC) was detected using ceftaroline E‑test strips. Results: Twenty‑eight MRSA isolates (93.33%) were found to be susceptible to ceftaroline. Conclusion: Ceftaroline demonstrated promising potency and coverage against MRSA isolates and can be considered an effective alternative treatment keeping vancomycin and linezolid as a reserved option.

Study Of Antibiotic Resistance Pattern Of Enterococci With Special Reference To Newer Antibiotic.

Background: Multidrug-resistant Enterococci are major problem and are increasingly reported worldwide. Enterococcal infections have been associated with higher hospitalization costs and a higher number of related deaths. Treatment of multidrug-resistant enterococci has become a challenge in hospitals around the world due to the lack of reliable therapeutic options. So the present study was undertaken with the aim to know the antimicrobial resistantpattern of enterococcus to newer antibiotic. Methodology: 22 isolates of enterococcus resistant to the entire routinely tested antibiotic were further tested for newer antimicrobial agent linezolid, daptomycin, rifampin, synercid, teicoplanin, telavancin, vancomycin, gentamicin (HLG). Results: Among these 22 enterococci isolated none of our isolates showed resistance to vancomycin, teicoplanin, telavancin, tigecycline and linezolid. But one isolate of E.faecalis showed resistance to daptomcyin. This daptomycinnonsusceptible isolate was found susceptible to ceftaroline. E. faecalis showed higher resistance to Gentamicin (HLG) and Synercid as compared to E.faecium. Specimen-wise higher distribution of enterococci (resistant to routinely tested antimicrobial agents) was observed in Urine 11(50%) followed by Pus 4(18.18%) and Miscellaneous 4(18.18%) and from Blood 3(13.64%). Conclusion: In our study none of the isolates showed resistance to vancomycin, tigecycline, telavancin, linezolid and ceftaroline but thepresence of daptomycin non-susceptible enterococci 1(4.55%) in our rural set-up is cause of concern.

Susceptibilidad a ceftarolina en staphylococcus aureus meticilino resistente / Susceptibility ceftaroline in methicillin-resistant staphylococcus aureus

Ceftarolina es un antibiótico de última generación del subgrupo de las cefalosporinas. Es el primer beta-lactámico comercializado que presenta actividad frente a Staphylococcus aureus resistente a la meticilina (SARM). El objetivo del presente estudio fue describir el patrón de susceptibilidad a ceftarolina en SARM aislados en el Laboratorio de Microbiología del Hospital Vargas de Caracas. Material y métodos: El aislamiento e identificación de las cepas se realizo por pruebas bioquímicas convencionales y las pruebas de susceptibilidad por el método de Difusión en Disco según CLSI 2015. Resultados: Se analizaron un total de 100 cepas SARM, de las cuales el 100% resultó sensible para ceftarolina (≥ 24 mm), con un rango de 26-35 mm, no detectándose ninguna cepa intermedia ni resistente. Conclusión: Ceftarolina muestra una excelente actividad in vitro frente a SARM, por lo que podría presentarse como una alternativa prometedora en el tratamiento de infecciones causadas por este microorganismo.

Ceftaroline is an antibiotic of last generation cephalosporins subgroup. Is the first marketed beta-lactam having activity against Methicillin-resistant S. aureus (MRSA). The aim of this study was to describe the pattern of susceptibility to ceftaroline in MRSA isolated in the Microbiology Laboratory of Hospital Vargas of Caracas. Methods: Isolation and identification of the strains was performed by conventional biochemical tests and susceptibility testing by disk diffusion method according to CLSI 2015. Results: A total of 100 MRSA strains were analyzed, of which 100% he was sensitive to ceftaroline (≥ 24 mm), with a range of 26-35 mm, not detected any intermediate or resistant strain. Conclusion: Ceftaroline shows excellent in vitro activity against MRSA, so it could be presented as a promising alternative in the treatment of infections caused by this organism.

Activity of ceftaroline and comparators against pathogens isolated from skin and soft tissue infections in Latin America - results of AWARE surveillance 2012

ABSTRACT As part of the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) surveillance program in 2012 the in vitro activity of ceftaroline and relevant comparator antimicrobials was evaluated in six Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico and Venezuela) against pathogens isolated from patients with hospital associated skin and soft tissue infections (SSTIs). The study documented that ceftaroline was highly active (MIC90 0.25 mg/L/% susceptible 100%) against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MIC90 2 mg/L/% susceptible 83.3%) and ß-hemolytic streptococci (MIC90 0.008-0.015 mg/L/% susceptible 100%). The activity of ceftaroline against selected species of Enterobacteriaceae was dependent upon the presence or absence of extended-spectrum ß-lactamases (ESBLs). Against ESBL screen-negativeEscherichia coli, Klebsiella pneumoniae, andKlebsiella oxytoca the MIC90 and percent susceptible for ceftaroline were (0.5 mg/L/94.1%), (0.5 mg/L/99.0%) and (0.5 mg/L/91.5%), respectively. Ceftaroline demonstrated potent activity against a recent collection of pathogens associated with SSTI in six Latin American countries in 2012.

Ceftaroline activity tested against contemporary Latin American bacterial pathogens (2011)

A total of 2484 target bacterial pathogens were collected (one per patient episode) from patients in 16 Latin American medical centers located in seven nations during 2011. Isolate identity was confirmed at a coordinating laboratory and susceptibility testing was performed for ceftaroline and comparator agents according to reference broth microdilution methods. A total of 30.0% of isolates were from respiratory tract, 29.4% from skin and skin structure, 21.4% from blood stream, 7.9% from urinary tract and 11.3% from other sites. Ceftaroline was active againstStaphylococcus aureus (42.8% MRSA) with 83.6% of the isolates at <1mg/L and all isolates at <2mg/L (MIC5090, 0.25/2mg/L). National MRSA rates ranged from a low of 28.8% in Colombia to a high of 68.1% in Chile. All Streptococcus pyogenes and Streptococcus agalactiae were susceptible to ceftaroline (MIC50/90 values were at <0.015/<0.015mg/L for both). All Streptococcus pneumoniae were susceptible to ceftaroline, linezolid, tigecycline and vancomycin. Susceptibility to ceftriaxone was at 88.4% (CLSI non-meningitis interpretive criteria) and 73.9% (CLSI meningitis interpretive criteria) for all S. pneumoniae. Ceftriaxone susceptibility was only at 33.3% (CLSI non-meningitis interpretive criteria) and 0.0% (CLSI meningitis interpretive criteria) for penicillin-intermediate (penicillin MIC, 4mg/L) strains. AllHaemophilus influenzae (29.4% β-lactamase-positive) isolates were susceptible to ceftaroline, amoxicillin-clavulanate, ceftriaxone, and levofloxacin. For the Latin American region, the ESBL-phenotype rate was 37.6% for Escherichia coli and 53.3% for Klebsiella pneumoniae. Ceftaroline was not active against ESBL-phenotype strains but was active against >90.0% of the non-ESBL-phenotype. The spectrum of activity of ceftaroline against pathogens from Latin America indicates that it merits further study for its potential use in the Latin American region.

Spectrum and potency of ceftaroline against leading pathogens causing community-acquired respiratory tract and skin and soft tissue infections in Latin America, 2010

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with in vitro bactericidal activity against Gram-positive organisms, including methicillinsusceptible and -resistant Staphylococcus aureus, β-haemolytic and viridans group streptococci, and Streptococcus pneumoniae, as well as common Gram-negative organisms. In this study a total of 986 isolates collected in 2010 from patients in 15 medical centers in five Latin American countries from the Assessing Worldwide Antimicrobial Resistance Evaluation Program were identified as community-acquired respiratory tract or skin and soft tissue infection pathogens. Ceftaroline was the most potent agent tested against S. pneumoniae with a MIC90 value (0.12 µg/mL) that was eight-fold lower than ceftriaxone, levofloxacin, and linezolid. Its spectrum of coverage (100.0% susceptible) was similar to tigecycline, linezolid, levofloxacin and vancomycin. Against Haemophilus influenzae and Moraxella catarrhalis, ceftaroline was the most active agent tested. The activity of ceftaroline against S. aureus (including MRSA) was similar to that of vancomycin and tetracycline (MIC90,1 µg/mL) and linezolid (MIC90,2 Jg/mL). The 1-haemolytic streptococci exhibited 100.0% susceptibility to ceftaroline. Ceftaroline activity against Escherichia coli, Klebsiella spp., and Enterobacter spp. was similar to that of ceftriaxone and ceftazidime. These parenteral cephalosporin agents have potent activity against non-extended-spectrum These parenteral cephalosporin agents have potent activity against non-extended-spectrum-lactamase-phenotype strains, but are not active against extended-spectrum β-lactamase-phenotype strains. These results confirm the in vitro activity of ceftaroline against pathogens common in communityacquired respiratory tract and skin and soft tissue infection in Latin America, and suggest that ceftaroline fosamil could be an important therapeutic option for these infections.