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Rev Esp Quimioter 2022;35(Suppl.2):28-34

Pharmacokinetics/Pharmacodynamics and tolerability of cefiderocol in the clinical setting

JOSÉ RAMÓN AZANZA PEREA, BELÉN SÁDABA DÍAZ DE RADA

Published: 4 October 2022

Cefiderocol is a new cephalosporin with a catechol in its chemical structure faciliting its access to the interior of bacteria through iron channels. In addition, it is broadly stable to beta-lactamases. The pharmacokinetic profile is a beta-lactam one: no oral absorption, and with a wide distribution within the vascular space and the interstitial fluid of well vascularized tissues, reaching therapeutic concentrations in the alveolar lavage fluid and within the macrophage. The binding of cefiderocol to human plasma proteins, primarily albumin, is moderate (range 40-60%). The terminal elimination half-life in healthy adult subjects was 2 to 3 hours. Cefiderocol is mainly renally eliminated, so dose adjustments are recommended in subjects with moderate / severe renal impairment, in case of dialysis, and probably in patients with external clearance. Like other beta-lactams, the PK / PD parameter that has been shown to best correlate with efficacy is the efficacy time of unbound plasma concentrations (%fT>MIC), which must be close to 100% to achieve a bactericidal effect. This is possible with 2 g in a 3-hour infusion every 8 hours. In controlled trials appears to be well tolerated, similar to comparators: meropenem or imipenem-cilastatin. Cefiderocol has no apparent clinically significant effect on ECG parameters nor on plasma iron values.

http://www.doi.org/10.37201/req/s02.04.2022

Rev Esp Quimioter 2022; 35(Suppl. 2):28-34 [Full-text PDF]


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Rev Esp Quimioter 2022;35(Suppl.2):20-27

Antibacterial spectrum of cefiderocol

DESIRÉE GIJÓN CORDERO, JUAN ANTONIO CASTILLO-POLO, PATRICIA RUIZ-GARBAJOSA, RAFAEL CANTÓN

Published: 4 October 2022

Cefiderocol, a siderophore catechol cephalosporin, recently introduced in the market has been developed to enhance the in vitro activity of extended spectrum cephalosporins and to avoid resistance mechanisms affecting cephalosporins and carbapenems. The in vitro study of cefiderocol in the laboratory requires iron depleted media when MIC values are determined by broth microdilution. Disk diffusion presents good correlation with MIC values. In surveillance studies and in clinical trials it has been demonstrated excellent activity against Gram-negatives, including carbapenemase producers and non-fermenters such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Few cefiderocol resistant isolates have been found in surveillance studies. Resistance mechanisms are not directly associated with porin deficiency and or efflux pumps. On the contrary, they are related with gene mutations affecting iron transporters, AmpC mutations in the omega loop and with certain beta-lactamases such us KPC-variants determining also ceftazidime-avibactam resistance, certain infrequent extended-spectrum betalactamases (PER, BEL) and metallo-beta-lactamases (certain NDM variants and SPM enzyme).

http://www.doi.org/10.37201/req/s02.03.2022

Rev Esp Quimioter 2022; 35(Suppl. 2):20-27 [Full-text PDF]


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Rev Esp Quimioter 2022;35(Suppl.2):16-19

Mechanism of action of cefiderocol

ALEX SORIANO, JOSEP MENSA

Published: 4 October 2022

Gram-negative bacilli are intrinsically resistant to many antibiotics due to the low permeability of their outer membrane. The most effective strategy to solve this problem has been the design of antibiotics that cross the membrane using specific transport systems. This is the case of cefiderocol, which, unlike cefepime or ceftazidime, has a chlorocatechol group at the end of the C-3 side chain. This group is recognized by transporters located in the outer membrane that allow cefiderocol to accumulate in the periplasmic space. Furthermore, cefiderocol is not a substrate for efflux pumps and the configuration of the side chains at C-7 and in particular at C-3 confer it a high stability against hydrolysis by most beta-lactamases of clinical interest including class A (KPC, BLEEs), C (ampC) or D (OXA-48) serine beta-lactamases and metallo-betalactamases (NDM, VIM. IMP). In order to better understand the mechanism of action of cefiderocol, the importance of iron in bacterial metabolism and the competition for iron between bacteria and host are reviewed.

http://www.doi.org/10.37201/req/s02.02.2022

Rev Esp Quimioter 2022; 35(Suppl. 2):16-19 [Full-text PDF]


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Rev Esp Quimioter 2022;35(Suppl.2):1-15

Resistance to beta-lactams in Gram-negative bacilli: relevance and potential therapeutic alternatives

VÍCTOR GARCIA-BUSTOS, MARTA DAFNE CABAÑERO-NAVALÓN, MIGUEL SALAVERT LLETÍ

Published: 4 October 2022

The indiscriminate and massive antibiotic use in the clinical practice and in agriculture or cattle during the past few decades has produced a serious world health problem that entails high morbidity and mortality: the antibiotic multi-drug resistance. In 2017 and 2019, the World Health Organization published a list of urgent threats and priorities in the context of drug resistance, which only included Gram-negative bacteria and specially focused on carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, as well as carbapenem and third generation cephalosporin-resistant Enterobacteriaceae. This scenario emphasizes the need of developing and testing new antibiotics from different families, such as new beta-lactams, highlighting cefiderocol and its original mechanism of action; new beta-lactamase inhibitors, with vaborbactam or relebactam among others; new quinolones such as delafloxacin, and also omadacycline or eravacycline, as members of the tetracycline family. The present work reviews the importance and impact of Gram-negative bacterial infections and their resistance mechanisms, and analyzes the current therapeutic paradigm as well as the role of new antibiotics with a promising future in the era of multi and pan-drug resistance.

http://www.doi.org/10.37201/req/s02.01.2022

Rev Esp Quimioter 2022; 35(Suppl. 2):1-15 [Full-text PDF]


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Rev Esp Quimioter 2022; 35(6):577-578

Myroides odoratus as an unusual urinary tract infection pathogen in immunosuppressed patient

ANA ALBEROLA ROMANO, CRISTINA GÓMEZ-CAMARASA, LUCÍA PÉREZ RODRÍGUEZ, ALBERTO VÁZQUEZ BLANQUIÑO, NATALIA CHUECA PORCUNA

Published: 3 October 2022

LETTER TO THE EDITOR

http://www.doi.org/10.37201/req/045.2022

Rev Esp Quimioter 2022; 35(6):577-578  [Full-text PDF]


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Rev Esp Quimioter 2022; 35(6):572-576

Nosocomial meningitis caused by ESBL- and OXA-48-producing Klebsiella pneumoniae and treated with ceftazidime-avibactam. Report of one case and review of the literature

LUCÍA B VALIENTE DE SANTIS, IGNACIO MÁRQUEZ GÓMEZ, BEATRIZ SOBRINO DÍAZ, INÉS PÉREZ CAMACHO, CONCEPCIÓN MEDIAVILLA GRADOLPH, LUIS F CABALLERO MARTÍNEZ, FRANCISCO J VICENTE HERNÁNDEZ, LAURA CASTELO CORRAL, MARCIAL DELGADO FERNÁNDEZ, ANTONIO PLATA CIÉZAR, JUAN D RUIZ MESA, JOSÉ M REGUERA IGLESIAS

Published: 3 October 2022

LETTER TO THE EDITOR

http://www.doi.org/10.37201/req/043.2022

Rev Esp Quimioter 2022; 35(6):572-576  [Full-text PDF]


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Rev Esp Quimioter 2022; 35(6):538-543

Evaluation of two immunocromatographic tests for the detection of antibodies against SARS-CoV-2

SARA MEDRANO, MERCEDES MARTÍNEZ-RODRÍGUEZ, LUIS VALLEJO, ESTHER CULEBRAS, ALBERTO DELGADO-IRIBARREN

Published: 27 September 2022

http://www.doi.org/10.37201/req/019.2022

Introduction. Serological tests have been a valuable tool during the SARS-CoV-2 pandemic, supporting molecular methods for detection, and monitoring the immune response, caused by vaccination or by natural infection. Within all these techniques, rapid tests are interesting due to their ease of use, rapid response and low cost.
Methods. Two different immunological techniques were evaluated: Realy Tech and Mikrogen Diagnostik recomLine SARS-CoV-2 IgG. SARS-CoV-2 IgG II Quant antibody test and SARS-CoV-IgG assay, both from Abbott Diagnostics, were used as reference techniques.
Results. Mikrogen Diagnostik recomLine SARS-CoV-2 IgG shows the best results (S=0.985; E=0.839). Three techniques offered good positive predictive values, but Realy Tech and Healgen negative predictive values left to be desired.
Conclusions. Mikrogen Diagnostik recomLine SARS-CoV-2 IgG showed good results in the detection of antibodies against SARS-CoV-2 and could be used as an alternative to automated techniques.

Rev Esp Quimioter 2022; 35(6):538-543 [Texto completo PDF]


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Rev Esp Quimioter 2022; 35(6):551-558

Impact of the use of antibiotics on the clinical response to immune checkpoint inhibitors in patients with non-small cell lung cancer

CRISTINA MARTINEZ-MUGICA BARBOSA, ANA CRISTINA CERCÓS LLETÍ, RUBÉN PAMPÍN SÁNCHEZ, CRISTINA DURÁN ROMÁN, PALOMA TERROBA ALONSO, BEATRIZ FERNÁNDEZ GONZÁLEZ

Published: 23 September 2022

http://www.doi.org/10.37201/req/040.2022

Objectives. Recent research suggests that the use of antibiotics could reduce the efficacy of checkpoint inhibitors, in addition to other well-known factors. It could be due to gut microbiota modification, which impact over the immune system response. However, the information available so far is contradictory. The objective of this research was to clarify whether antibiotic use influences efficacy of checkpoint inhibitors treatments in non-small cell lung cancer patients in clinical practice.
Methods. Therefore, a retrospective observational study was designed. Use of antibiotics among patients treated with atezolizumab, pembrolizumab or nivolumab was assessed within 2 months of checkpoint inhibitors treatments initiation.
Results. A total of 140 patients were included, mostly men, with good performance status (ECOG 0-1), all of them previously treated with chemotherapy. An antibiotic prescription was identified in 31% of these patients, mainly fluoroquinolones or beta-lactams. The most frequent indication was respiratory infection. Both progression-free survival and overall survival were lower for patients treated with anti-infective drugs, although this difference was not statistically significant.
Conclusion. More studies are needed to draw conclusions about the impact of antibiotics on the efficacy of immunotherapy.

Rev Esp Quimioter 2022; 35(6):551-558 [Full-text PDF]


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Rev Esp Quimioter 2022; 35(6):559-562

Limitations of the Xpert-MTB/RIF® assay in the initial diagnosis of tuberculosis in the context of a rural hospital in Ethiopia

BELÉN COMECHE, MARIO PÉREZ-BUTRAGUEÑO, JUAN CUADROS, GEBRE TIZIANO, MIGUEL GÓRGOLAS, JOSÉ-MANUEL RAMOS-RINCÓN

Published: 22 September 2022

http://www.doi.org/10.37201/req/052.2022

Introduction. To evaluate the implementation of Xpert-MTB/RIF®, as an early diagnosis technique, in a rural area of Ethiopia.
Material and methods. Data were retrospectively collected from those patients over 13 years of age who were requested to take the Xpert MTB/RIF® test in a rural hospital located 45 km from the reference laboratory, during the first 3 years of its implementation (2015, April -2018, April).
Results. A total of 306 patients older than 13 years were evaluated, in 85 (27.8%) there was an error in the processing of the test and the result was not obtained. Of the 221 samples with results, the median time between obtaining the sample and receiving the result was 21 days and 42 of them were positive (19%, 95% CI: 14.2-24.9%). The sample with the highest diagnostic yield was adenopathy (88.8%; [8/9]; p<0.001).
Conclusions. There are more bacteriological diagnoses with Xpert-MTB/RIF®, but with a delay in obtaining the result and its main objective, which is early diagnosis, is not achieved.

Rev Esp Quimioter 2022; 35(6):559-562 [Texto completo PDF]


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Rev Esp Quimioter 2022; 35(6):563-565

Impacto de la COVID-19 en el diagnóstico tardío de VIH: a propósito de un caso

ALEJANDRA ROMANO CARDOZO, LUIS SAINZ COMAS, MONTSERRAT SERES ROIG, AITOR ALQUÉZAR-ARBÉ

Published: 15 September 2022

LETTER TO THE EDITOR

http://www.doi.org/10.37201/req/143.2021

Rev Esp Quimioter 2022; 35(6):563-565  [Texto completo PDF]


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