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Rev Esp Quimioter 2022; 35(6):544-550

Clinical characteristics and prognosis of Staphylococcus aureus bacteremia

ROSA GARCÍA FENOLL, MARÍA ESPINOSA PÉREZ, SARAY MORMENEO BAYO, VIOLETA FRUTOS MILLÁN, MARÍA CARMEN MARTÍNEZ JIMÉNEZ, ROSA MARÍA MARTÍNEZ ÁLVAREZ, MARÍA PILAR PALACIÁN RUIZ, MARÍA CRUZ VILLUENDAS USÓN, CARLOS RAMOS PAESA

Published: 7 October 2022

http://www.doi.org/10.37201/req/035.2022

Introduction. Staphylococcus aureus bacteremia patients characteristics at a tertiary hospital are described, and complications, mortality and associated factors are analyzed.
Methods. Data from patients with S. aureus bacteremia admitted between March 2020 and February2021 at Miguel Servet university hospital in Zaragoza were retrospectively analyzed.
Results. Results showed a 14 days mortality of 24.2% and an 30 days mortality of 40%. Overall survival decreased with complications appearance [HR 3.1 (1.2-8.05)] and age over 65 years [HR 3.1 (1.4-6.6)]. The adjusted analysis showed correlation between a higher mortality at 14 and 30 days with age over 65 years [OR 6.3 (1.7-23.1)], sepsis presence [OR 19.3 (5.4-68.7)] and number of positive (+) blood cultures ≥3 [OR 5.4 (0.8-34.1)]. Mortality at 14 days was associated with sepsis presence [OR 58.2 (5.7-592.9)], number of positive (+) blood cultures ≥3 [OR 14.1 (1.1-173.7)] and an older age [OR 1.1 (1.03-1.1)]. Analyzing time to positive blood cultures ≤12 hours and number of positive blood cultures ≥ 3 at the same time, frequency of sepsis increased [30 patients (66.6%) vs 15 patients (33.3%); OR 3.4 (IC95% 1.5-8)].
Conclusions. High 14- and 30-days mortality were found, as well as a worse evolution in older age patients, with sepsis presence, and with greater number of positive blood cultures and times to positive blood cultures ≤12 h.

Rev Esp Quimioter 2022; 35(6):544-550 [Texto completo PDF]


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Rev Esp Quimioter 2022;35(Suppl.2):45-47

Cefiderocol. Summary and conclusions

JOSÉ MENSA, JOSÉ BARBERÁN

Published: 4 October 2022

http://www.doi.org/10.37201/req/s02.07.2022

Rev Esp Quimioter 2022; 35(Suppl. 2):45-47 [Full-text PDF]


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Rev Esp Quimioter 2022;35(Suppl.2):39-44

The role of cefiderocol in clinical practice

EMILIO MASEDA, ALEJANDRO SUÁREZ DE LA RICA

Published: 4 October 2022

Cefiderocol is a new antimicrobial with a chemical structure similar to ceftazidime and cefepime. In this review we will focus on the role of cefiderocol in different clinical scenarios produced by resistant Gram-negative microorganisms, especially to carbapenems. In infections caused by Gram-negative microorganisms, inappropriate antibiotic treatment increased the risk of mortality almost fourfold.
In patients with hospital-acquired infection and septic shock; with sepsis and poor functional reserve due to fragility; in immunocompromised patients; and in those with local ecology, individual history of colonization or previous infection and risk factors for carbapenem-resistant Enterobacteriaceae (CRE) such as the presence of chronic multi-morbidities, the best option would be to start an active empirical treatment against gram-negative bacteria resistant to carbapenems and later in 24-36 h with the information obtained from the cultures we could decide on a definitive empirical or directed treatment and avoid unnecessary overuse of these antibiotics. Cefiderocol would be in these cases a good candidate due to its excellent in vitro activity against all classes of beta-lactamase-producing Gram-negatives (including carbapenemase class A, B and D producers), as well as against non-fermenting Gram-negatives such as P. aeruginosa, Acinetobacter spp. and S. maltophilia. It is necessary to optimize the use of new antibiotics such as cefiderocol, guaranteeing the best available treatment to patients while delaying the emergence and spread of resistance.

http://www.doi.org/10.37201/req/s02.06.2022

Rev Esp Quimioter 2022; 35(Suppl. 2):39-44 [Full-text PDF]


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Rev Esp Quimioter 2022;35(Suppl.2):35-38

Clinical experience of cefiderocol

MARÍA CARMEN FARIÑAS

Published: 4 October 2022

Infections by antibiotic-resistant microorganisms could be considered a “stealth pandemic” that we fight daily in most hospitals. Some estimates suggest that today 700,000 deaths per year can be attributed to antimicrobial resistance. By the year 2050, it is estimated that this will increase to ten million deaths per year as a result of infections by multidrug-resistant microorganisms. In this context, the availability of antimicrobial therapy that is effective against these pathogens is essential to be able to “save the lives” of our patients. Cefiderocol, a new cephalosporin with a different mechanism of action, will be an essential treatment in many infections caused by resistant aerobic gram-negative bacteria. Cefiderocol has been used to treat patients with complicated urinary tract infections (cUTI); hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), healthcare-associated pneumonia (HAP); in patients with sepsis and bacteremia, some without an identified primary focus of infection.

http://www.doi.org/10.37201/req/s02.05.2022

Rev Esp Quimioter 2022; 35(Suppl. 2):35-38 [Full-text PDF]


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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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