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Rev Esp Quimioter 2019; 32(Suppl. 2):35-37

The pharmacodynamic bases of the prescription of antimicrobials  

JOSÉ RAMÓN AZANZA PEREA

In the past, the dose of an antibiotic was chosen, always from among those that were well tolerated, by considering those with the ability to exceed the MIC of bacteria in plasma. This approach, which has still not widely changed, is contrast-ed with the pharmacokinetic and pharmacodynamic (PK/PD) relationships, which indicate that the efficacy of antibiotics is directly related to parameters that relate the sequence of con-centrations over time with a parameter of the MIC effect in vitro. Until now, three types of PK/PD relationships have been established for antibiotics: the inhibitory coefficient (Cmax/MIC), the efficacy time (T>CMI) and the relationship between the exposure of the drug and the MIC (AUC/MIC).

Rev Esp Quimioter 2019; 32(Suppl. 2):35-37 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(Suppl. 2):32-34

Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa  

CELIA CARDOZO, VERÓNICA RICO, DAIANA AGÜERO, ALEX SORIANO

Pseudomonas aeruginosa is characterized by an important intrinsic resistance to antibiotics and it possess an extraordinary ability to develop resistance to nearly all available antimicrobials through selection of mutations. We review some of the pharmacodynamic principles of antibiotics predicting efficacy, clinical experience with monotherapy and combination therapy, and principles for antibiotic treatment for empirical and directed treatment of P. aeruginosa invasive infections.

Rev Esp Quimioter 2019; 32(Suppl. 2):32-34 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(Suppl. 2):27-31

Current status of ESKAPE microorganisms in Spain: Epidemiology and resistance phenotypes  

JAVIER SÁNCHEZ-LÓPEZ, RAFAEL CANTÓN

Resistance rates in ESKAPE microorganisms included in the EARS-net surveillance database from Spain have increased in most of the cases. In 2017, multi-drug resistant isolates rose to 5.5% in Escherichia coli and 13.0% in Klebsiella pneumoniae. Carbapenemase producing Enterobacterales (CPE) have also increased in Spain over the last years with a current spread of throughout the country. EuSCAPE project revealed dominance of OXA-48 carbapenemase with lower prevalence of KPC, VIM or NDM enzymes. Increase of faecal carriers and presence of carbapenemases in the so-called high-risk clones have boosted the persistence and dissemination of CPE. One of these clones, the ST307 K. pneumoniae, has been associated with the spread of KPC carbapenemases and emergence of KPC variants conferring resistance to ceftazidime-avibactam combination.

Rev Esp Quimioter 2019; 32(Suppl. 2):27-31 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(Suppl. 2):1-9

Update in Infectious Diseases 2019  

FRANCISCO JAVIER CANDEL, CARLA MARGARITA RICO, IRENE DÍAZ DE LA TORRE, BERTA LAGUNA, JORGE MARTÍNEZ-JORDÁN, SARA MEDRANO, MAURICIO CÉSAR ESCOBAR-PORCEL, ANGEL LÓPEZ-DELGADO, LAURA LÓPEZ-GONZÁLEZ, JOSE MANUEL VIÑUELA-PRIETO, MAYRA MATESANZ, JUAN GONZÁLEZ DEL CASTILLO, ANA ARRIBI

The IX Course of Antimicrobials and Infectious Diseases update included a review of the main issues in clinical microbiology, epidemiology and clinical aspects for a current approach of infectious pathology. The present introduction summarizes about the most important meetings related to infectious diseases during 2018 (ECCMID, IAS, ASM and ID Week). In addition, the course provides a practical information to focus on nosocomial infection models, with immunosuppressed patients or complex multidrug-resistant pathogens. The closing lecture of this year reviewed the infection during donation process.

Rev Esp Quimioter 2019; 32(Suppl. 2):1-9 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(Suppl. 3):34-36

Safety and tolerability of ceftobiprole  

SANTIAGO GRAU

Ceftobiprole is a fifth generation cephalosporin with a series of characteristics differentiating it from other beta-lactams, including its antibacterial activity, mainly against methicillin-resistant Staphylococcus aureus, resistant Streptococcus pneumoniae and also Gram-negative microorganisms such as Pseudomonas aeruginosa. This antibiotic has been subjected to various clinical trials and the results of these have led to its approval in Spain for the treatment of nosocomial pneumonia, excluding that associated with mechanical ventilation, and community-acquired pneumonia. The results of various ceftobiprole clinical studies provide consistent information on efficacy and tolerability. Ceftobiprole as monotherapy has been shown to be non-inferior to comparator antibiotics in different settings. Information is available on its compatibility with other drugs in Y-site administration, important from the point of view of the intravenous treatment of patients who present venous access limitation. On the other hand, and in contrast to other cephalosporins, ceftobiprole presents a low risk of infection due to Clostridium difficile and, in comparison with ceftaroline, neutropenia has not been reported to present any significant issues.

Rev Esp Quimioter 2019; 32(Suppl. 3):34-36 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(Suppl. 3):29-33

Possible clinical indications of ceftobiprole  

JOSÉ BARBERÁN

Ceftobiprole is a fifth-generation cephalosporin approved for the treatment of adult community-acquired pneumonia and non-ventilator associated hospital-acquired pneumonia. However, its microbiological and pharmacokinetic profile is very attractive as armamentarium for empirical monotherapy treatment in other infections too. Among these, the following scenarios could be considered complicated skin and soft tissue infections, moderate-severe diabetic foot infections without bone involvement, vascular-catheter-associated-bloodstream infections, and fever without apparent focus in the hospitalized patient without septic shock or profound immunosuppression.

Rev Esp Quimioter 2019; 32(Suppl. 3):29-33 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(Suppl. 3):24-28

Ceftobripole: Experience in staphylococcal bacteremia  

ALEX SORIANO, LAURA MORATA

Ceftobiprole is a new cephalosporin with an extended spectrum activity against the majority of microorganisms isolated in bacteremia including methicillin-susceptible (MSSA) and -resistant S. aureus (MRSA). This antibiotic has demonstrated a potent activity against MRSA in animal models of endocarditis in monotherapy but particularly in combination with daptomycin, suggesting that this combination could be a future option to improve the outcome of staphylococcal endovascular infections. In addition, the extended-spectrum ceftobiprole activity, including coagulase-negative staphylococci, Enterococcus faecalis, Enterobacteriaceae and Pseudomonas aeruginosa represents an advantage for use as empirical therapy in bacteremia potentially caused by a broad spectrum of microorganisms, such as in catheter-related bacteremia.

Rev Esp Quimioter 2019; 32(Suppl. 3):24-28 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(Suppl. 3):17-23

Ceftobiprole for the treatment of pneumonia  

CATIA CILLÓNIZ, CRISTINA DOMINEDÒ, CAROLINA GARCIA-VIDAL, ANTONI TORRES

Ceftobiprole is a fifth-generation cephalosporin with potent antimicrobial activity against Gram positive and Gram-negative bacteria. It has been approved in major European countries for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia (VAP). Ceftobiprole is currently in a phase 3 clinical program for registration in the U.S. In 2015, it was designated as an infectious disease product qualified for the treatment of lung and skin infections by the FDA. The efficacy of ceftobiprole in pneumonia has been demonstrated in two-phase III clinical trials conducted in patients with CAP and HAP. The recommended dose in the adult with pneumonia is 500 mg every 8 h infused in 2 h; in case of renal failure, the regimen of administration must be adjusted according to the patient’s renal function. It is not necessary to adjust the dose according to gender, age, body weight or liver failure. In case of hyperfiltration, an extension to 4 h infusion of the 500mg TID is required.

Rev Esp Quimioter 2019; 32(Suppl. 3):17-23 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(Suppl. 3):11-16

Ceftobiprole: pharmacokinetics and PK/PD profile  

JOSÉ RAMÓN AZANZA PEREA, BELÉN SÁDABA DÍAZ DE RADA

Ceftobiprole shows many similar pharmacokinetic properties to other cephalosporins, except for not being orally bioactive, and that it is administered by IV infusion as the prodrug ceftobiprole medocaril, which is subsequently hydrolyzed in the blood into the active molecule. Distribution focus in extracellular fluid and active antibiotic concentration has been proven in different corporal tissues using dosing regimen of 500 mg intravenous infusion over 2 h every 8 h. Ceftobiprole is eliminated exclusively into the urine, thus the reason why dose adjustment is required for patients with moderate or severe renal impairment, or increased creatinine clearance. However, there is no need for dose adjustments related with other comorbidities and patients’ conditions such as age, body weight. Although considering distribution features, molecular weight and dose fraction, increase dosing regimen might be necessary in patients using renal replacement therapy. The half-life of ceftobiprole is more than 3 h, allowing to easily reach optimal PK/PD parameters with the infusion time of 2 h, using the usual dosing regimen.

Rev Esp Quimioter 2019; 32(Suppl. 3):11-16 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(Suppl. 3):03-10

Mechanisms of action and antimicrobial activity of ceftobiprole  

MARÍA-ISABEL MOROSINI, MARÍA DÍEZ-AGUILAR, RAFAEL CANTÓN

Ceftobiprole, a novel last generation parenteral cephalosporin, has an extended spectrum of activity, notably against methicillin-resistant Staphylococcus aureus (MRSA), ampicillin-susceptible enterococci, penicillin-resistant pneumococci, Enterobacterales and susceptible Pseudomonas aeruginosa. It exerts an inhibitory action on essential peptidoglycan transpeptidases, interfering with cell wall synthesis. The inhibitory action of ceftobiprole through binding to abnormal PBPs like PBP2a in methicillin-resistant staphylococci and PBP2b and PBP2x in the case of ß-lactam-resistant pneumococci, ultimately leads to rapid bacterial cell death. In the case of Enterobacterales, ceftobiprole retains activity against narrow spectrum ß-lactamases but is hydrolysed by their extended-spectrum counterparts, overexpressed Amp C, and carbapenemases. It is also affected by certain efflux pumps from P. aeruginosa. For anaerobic bacteria, ceftobiprole is active against Gram-positive Clostridioides difficile and Peptococcus spp. and Gram-negative Fusobacterium nucleatum but not against Bacteroides group or other anaerobic Gram-negatives. In in vitro studies, a low propensity to select for resistant subpopulations has been demonstrated. Currently, ceftobiprole is approved for the treatment of community-acquired pneumonia and hospital-acquired pneumonia with the exception of ventilator-associated pneumonia. Ceftobiprole’s place in therapy appears to lie mainly in its combined activity against Gram-positive organisms, such as S. aureus and S. pneumoniae alongside that against Gram-negative organisms such as P. aeruginosa.

Rev Esp Quimioter 2019; 32(Suppl. 3):03-10 [Full-text PDF]

 

 

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