In Vitro Activity of Cefiderocol Compared to Other Antimicrobials against a Collection of Metallo-Beta-Lactamase-Producing Gram-Negative Bacilli from Southern Spain.

In this study, we aimed to comparatively evaluate the in vitro activity of cefiderocol versus other antimicrobials against a well-characterized collection of metallo-beta-lactamase (MBL)-producing Gram-negative bacilli (MBL-GNB) isolates from hospitals in Andalusia, Spain. We recovered 232 MBL-GNB from Andalusian hospitals, including 160 Enterobacterales and 72 nonfermenting Gram-negative bacilli belonging to 44 different clones (2015 to 2020). Cefiderocol and comparator MICs were determined with commercial methods (UMIC [Bruker] and EUMDROXF [Sensititre; Thermo Fisher], respectively). EUCAST breakpoints were used for all antimicrobials tested, and CLSI also was used for cefiderocol. Control strains used were E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. Cefiderocol showed potent in vitro activity against isolates tested, regardless of breakpoint (susceptibility rates, 85.3% for EUCAST versus 96.6% for CLSI, P < 0.001). MIC ranges for Enterobacterales and nonfermenting Gram-negative bacilli (NF-GNB) were ≤0.03 to 1 mg/L and 0.06 to 2 (IMP), 0.06 to 8 mg/L and 0.06 to 16 (VIM), 0.25 to 16 mg/L and 2 to 16 mg/L (NDM), respectively, and 0.25 to 8 mg/L for double MBL-producing Enterobacterales. By species, all cefiderocol-susceptible rates were over 90%, except Klebsiella oxytoca, Enterobacter cloacae, Escherichia coli, and Acinetobacter spp. Significant differences were observed comparing resistant isolates between Enterobacterales and NF-GNB by EUCAST (19.4% versus 4.2%, P < 0.01), but not by CLSI (4.4% versus 1.4%, P = 0.2). Cefiderocol was the most active antimicrobial tested. Cefiderocol showed excellent in vitro activity against MBL-GNB, especially NF-GNB; almost all isolates resistant to comparators were susceptible. IMPORTANCE This article demonstrates the efficacy of cefiderocol against a large collection of well-characterized metallo-beta-lactamase-producing isolates, some of them even producing double carbapenemases. Furthermore, cefiderocol activity is compared to other novel broad-spectrum antimicrobials with activity against carbapenemases.

[Infections in patients colonized with carbapenem-resistant Gram-negative bacteria in a medium Spanish city]. / Infecciones en pacientes colonizados con bacterias gramnegativas resistentes a carbapenémicos en una ciudad media española.

OBJECTIVE: Because there are few studies on the clinical implications of colonization by carbapenem-resistant gram-negative bacteria (CRB) this was analyzed in rectal smears (RS) and pharyngeals (PS) and its ability to predict infection/colonization. METHODS: A cross-sectional, retrospective study from adult inpatients between January 2016 and December 2019 was conducted. The isolates were characterized by MicroScan and spectrometry of masses applying EUCAST 2018 cutoff points. The detection of carbapenemases was performed by PCR and Sanger sequencing; sequencies was assigned by MLST. The genetic relationship between the clinical isolates was made by pulsed field electrophoresis using the enzymes Xbal, Spel or Apal. RESULTS: A total of 308 (86.03%) RS and 50 (13.97%) positive PS were detected, the RS had a 85% sensibility, 100% specificity, 100% positive predictive value and 97% negative predictive value. In RS, the following were isolated: 44% (n=135) Acinetobacter baumannii, 26% (n =80) Enterobacterales (20 KPC, 29 OXA-48, 22 VIM, 2 IMP, 7 NDM), 17% (n=53) Pseudomonas aeruginosa and 13% (n=40) Stenotrophomonas maltophilia. In the PS were isolated 44% (n=22) S. maltophilia, 40% (n = 20) A. baumannii, 8% (n=4) P. aeruginosa and 8% (n=4) Enterobacterales (3 VIM, 1 OXA). From the patients with simultaneous RS and PS, 41 (40.6%) had positivity in both smears, 45 (44.6%) only in RS and 15 (14.9%) only in PS. Colonization preceded infection in 81.3% (n=13) of the isolates; association between infection and colonization was found (p<0.001; χ2); and the episodes where the information was found all the isolates from the clinical samples and from the smears were similar. CONCLUSIONS: The probability of predicting infection through the CRB colonized in different clinical samples is feasible. The RS has a major sensibility to detect colonization.

Physicochemical and microbiological stability of two news oral liquid formulations of clonidine hydrochloride for pediatric patients.

Pediatric patients present changing physiological features. Because of the lack of land suitable for commercial management, pediatric specialties very often need to prepare extemporaneous formulations to improve the dosage and administration of drugs for children. Oral liquid formulations are the most suitable for pediatric patients. Clonidine is widely used in the pediatric population for opioid withdrawal, hypertensive crisis, attention deficit disorders and hyperactivity syndrome, and as an analgesic in neuropathic cancer pain. The objective was to study the physicochemical and microbiological stability and determine the shelf life of an oral solution containing 20 µg/mL clonidine hydrochloride in different storage conditions (5 ± 3 °C, 25 ± 3 °C, and 40 ± 2 °C). Using raw material with excipients safe for all pediatric age groups, two oral liquid formulations of clonidine hydrochloride were designed (with and without preservatives). Solutions stored at 5 ± 3 °C (with and without preservatives) were physically and microbiologically stable for at least 90 days in closed containers and for 42 days after opening. Two oral solutions of clonidine hydrochloride 20 µg/mL were developed for pediatric use from raw materials that are readily available and easy to process, containing safe excipients that are stable over a long period of time.

First report of linezolid dependence in methicillin-resistant Staphylococcus aureus.

Linezolid is used to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We describe the first report of linezolid dependence in MRSA. The strain was isolated from a respiratory sample of a cystic fibrosis patient, and it showed a thymidine-dependent small-colony variant phenotype. The effect was not related to any known mechanisms implicated in S. aureus resistance to linezolid. The clinical significance of this phenomenon needs further investigation.