Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant non-fermentative Gram-negative bacillus, posing a significant challenge in clinical treatment due to its numerous intrinsic and acquired resistance mechanisms. This study aimed to evaluate the adequacy of antibiotics used for the treatment of S. maltophilia infections in critically ill patients using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The antibiotics studied included cotrimoxazole, levofloxacin, minocycline, tigecycline, cefiderocol, and the new combination aztreonam/avibactam, which is not yet approved. By Monte Carlo simulations, the probability of target attainment (PTA), the PK/PD breakpoints, and the cumulative fraction of response (CFR) were estimated. PK parameters and MIC distributions were sourced from the literature, the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and the SENTRY Antimicrobial Surveillance Program collection. Cefiderocol 2 g q8h, minocycline 200 mg q12h, tigecycline 100 mg q12h, and aztreonam/avibactam 1500/500 mg q6h were the best options to treat empirically infections due to S. maltophilia. Cotrimoxazole provided a higher probability of treatment success for the U.S. isolates than for European isolates. For all antibiotics, discrepancies between the PK/PD breakpoints and the clinical breakpoints defined by EUCAST (or the ECOFF) and CLSI were detected.

Fosfomycin, a low molecular weight and hydrophilic drug with negligible protein binding, is eliminated almost exclusively by glomerular filtration, whose clearance is subject to patient renal function. The volume of distribution approximates to the extracellular body water (about 0.3 L/Kg) in healthy volunteers, but it is increased in critically ill patients with bacterial infections. Fosfomycin presents a high ability to distribute into many tissues, including inflamed tissues and abscess fluids. Based on PK/PD analysis and Monte Carlo simulations, we have evaluated different fosfomycin dosing regimen to optimize the treatment of septic patients due to Enterobacterales and Pseudomonas aeruginosa. As PK/PD targets, we selected %T >(MIC) > 70% for all pathogens, and AUC(24)/MIC > 24 and AUC(24)/MIC > 15 for net stasis of Enterobacterales and P. aeruginosa, respectively. Pharmacokinetic parameters in critically ill patients were obtained from the literature. Several dosing regimens were studied in patients with normal renal function: fosfomycin 2-8 g given every 6-12 hours, infused over 30 minutes- 24 hours. At the susceptibility EUCAST break-point for Enterobacterales and Staphylococcus spp. (MIC <= 32 mg/L), fosfomycin 4 g/8h or higher infused over 30 minutes achieved a probability of target attainment (PTA) > 90 %, based in both %T >(MIC) and AUC(24)/MIC. For MIC of 64 mg/L, fosfomycin 6 g/6h in 30-minute infusion and 8 g/ 8h in 30-minute and 6 hours infusions also achieved PTA values higher than 90%. No fosfomycin monotherapy regimen was able to achieve PK/PD targets related to antimicrobial efficacy for P. aeruginosa with MICs of 256-512 mg/L.

The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains.

Tedizolid and linezolid have antibacterial activity against the most important acute bacterial skin and skin-structure infection (ABSSSIs) pathogens. The objective of this work was to apply PK/PD analysis to evaluate the probability of attaining the pharmacodynamic target of these antimicrobials based on the susceptibility patterns of different clinical isolates causing ABSSSI. Pharmacokinetic and microbiological data were obtained from the literature. PK/PD breakpoints, the probability of target attainment (PTA) and the cumulative fraction of response (CFR) were calculated by Monte Carlo simulation. PTA and CFR are indicative of treatment success. PK/PD breakpoints of tedizolid and linezolid were 0.5 and 1 mg/L, respectively. Probability of treatment success of tedizolid was very high (>90%) for most staphylococci strains, including MRSA and coagulase-negative staphylococci (CoNS). Only for methicillin- and linezolid-resistant S. aureus (MLRSA) and linezolid resistant (LR) CoNS strains was the CFR of tedizolid very low. Except for LR, daptomycin-non-susceptible (DNS), and vancomycin-resistant (VRE) E. faecium isolates, tedizolid also provided a high probability of treatment success for enterococci. The probability of treatment success of both antimicrobials for streptococci was always higher than 90%. In conclusion, for empiric treatment, PK/PD analysis has shown that tedizolid would be adequate for most staphylococci, enterococci, and streptococci, even those LR whose linezolid resistance is mediated by the cfr gene.

Pseudomonas aeruginosa remains one of the major causes of healthcare-associated infection in Europe; in 2019, 12.5% of invasive isolates of P. aeruginosa in Spain presented combined resistance to ≥3 antimicrobial groups. The Spanish nationwide survey on P. aeruginosa antimicrobial resistance mechanisms and molecular epidemiology was published in 2019. Based on the information from this survey, the objective of this work was to analyze the overall antimicrobial activity of the antipseudomonal antibiotics considering pharmacokinetic/pharmacodynamic (PK/PD) analysis. The role of PK/PD to prevent or minimize resistance emergence was also evaluated. A 10,000-subject Monte Carlo simulation was executed to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) considering the minimum inhibitory concentration (MIC) distribution of bacteria isolated in ICU or medical wards, and distinguishing between sample types (respiratory and non-respiratory). Ceftazidime/avibactam followed by ceftolozane/tazobactam and colistin, categorized as the Reserve by the Access, Watch, Reserve (AWaRe) classification of the World Health Organization, were the most active antimicrobials, with differences depending on the admission service, sample type, and dose regimen. Discrepancies between EUCAST-susceptibility breakpoints for P. aeruginosa and those estimated by PK/PD analysis were detected. Only standard doses of ceftazidime/avibactam and ceftolozane/tazobactam provided drug concentrations associated with resistance suppression.

The identification of filamentous fungi by matrix-assisted laser desorption/ionization–time of flight mass spectrometry (MALDI–TOF MS) represents a challenge due to their complex taxonomy and the lack of comprehensive databases. The aim of this study was to evaluate the current status of available MALDI–TOF MS databases for the identification of dermatophytes, including commercial, in-house, and web-based databases. We collected 289 dermatophyte strains from different centers and analyzed them using four databases and a combination of them. The combination of commercial and in-house databases was shown to improve the identification rate and accuracy at the species level. For Trichophyton rubrum, the concordance among all databases was above 90.0%. For the T. mentagrophytes group, correct identification at the species level ranged from 30.0 to 78.9%, depending on the database, and showed very low agreement among them. The addition of the novel species T. japonicum to our in-house database resulted in the successful identification of this species. On the other hand, T. interdigitale and T. tonsurans were the species most frequently misidentified by MALDI–TOF MS. Through deep spectra analysis of both species, up to 29 protein peaks were found to be suitable for their differentiation, demonstrating the potential of peak analysis in differentiating closely related species. In conclusion, improvements of the databases with new strains resulted in increased identification accuracy at the species level. This, combined with peak analysis, could improve the overall identification of dermatophytes by MALDI–TOF MS in clinical laboratories.