Comparison between MALDI-TOF MS and MicroScan in the identification of emerging and multidrug resistant yeasts in a fourth-level hospital in Bogotá, Colombia.

BACKGROUND: The introduction of MALDI-TOF MS in the clinical microbiology laboratory has modified the approaches for the identification of fungi. Thanks to this tool, it is possible to identify cryptic species, which possess critical susceptibility patterns. Clinical strains were identified using the MicroScan and MALDI-TOF MS systems. Discrepant results from both methods were investigated using ITS rDNA barcoding. Finally, these isolates were also tested for in vitro susceptibility. RESULTS: The percentage of agreement between both methods to 498 yeast isolates was of 93.6% (32 discrepant isolates). The concordance of ITS sequencing with MALDI-TOF MS was higher (99%) than that of MicroScan (94%). Several of these discordant yeasts displayed high MICs for antifungal agents. CONCLUSIONS: Our study highlights the need of the MS and molecular approaches such as MALDI-TOF MS and ITS rDNA barcoding for the correct identification of emerging or cryptic yeast species; besides, some of these could be multidrug resistant. This work was the first experience in the implementation of the MALDI-TOF MS technology in Colombia. We found the first uncommon yeasts including Candida auris and we could identify Trichosporon faecalis. Our work highlights a clear necessity of an accurate yeast identification as a much more pertinent technique than the susceptibility profiles, because the most unusual yeasts exhibit resistance profiles to the few available antifungals.

First report of sporadic cases of Candida auris in Colombia.

BACKGROUND: Candida auris is a recently reported Candida species that is phenotypically similar to Candida haemulonii and related to hospital outbreaks. This organism can be misidentified as Candida haemulonii, Candida famata, Candida catenulata, or Rhodotorula glutinis by phenotypic approaches. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and DNA sequence analysis using internal transcribed spacer rDNA bar-coding provide an accurate identification. CASE REPORTS: Three cases of C. auris infection in patients with risk factors for fungal infection (one admitted to the intensive care unit, one with lymphoma, and one with HIV; all three with previous antibiotic use) are reported; these infections were not epidemiologically related. Yeast isolates were recovered from blood, ocular secretion, and bronchoalveolar lavage and were misidentified as C. catenulata and Candida albicans by the phenotypic MicroScan method. The isolates were confirmed to be C. auris by means of MALDI-TOF MS and DNA sequence analysis. Antifungal susceptibility testing was performed on these C. auris isolates, which exhibited high minimum inhibitory concentrations to triazoles and amphotericin B. One patient survived and the other two died. Only one of these deaths was related to fungemia. CONCLUSIONS: C. auris is an emerging and opportunistic multidrug-resistant human pathogen. It is necessary to strengthen measures to achieve an accurate and quick identification and also to avoid its dissemination. This will require improvements in health and infection control measures, as well as the promotion of antifungal stewardship in healthcare facilities.

Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy.

INTRODUCTION: Patients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center. METHODS: This was an open, nonrandomized, observational, descriptive, and prospective study. Samples from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy. Five blood samples were taken from each patient when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after each dose. Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis. All study participants provided written informed consent. RESULTS: We investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm³ (standard deviation (SD) ± 603.2). The following pharmacokinetic measurements were obtained: maximum concentration, 94.1-1133 mg/L; minimum concentration, 0.47-37.65 mg/L; volume of distribution, 0.08-0.65 L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42-27.25 L/h (mean, 9.93 L/h); half-life (t(1/2)), 0.55-2.65 h (mean, 1.38 h); and area under the curve, 115.12-827.16 mg · h/L. CONCLUSION: Patients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1(/2) and decreased CL.

Farmacocinética y farmacodinamia de antimicrobianos: a propósito de pacientes con neutropenia y fiebre / Pharmacokinetics and pharmacodynamics of antibacterial agents: on account of febrile neutropenic patients

Febrile neutropenia is a serious complication of antineoplastic therapy and it is more commonly found in hematologic patients, associated with high mortality rates. Inadequate tissue concentration of antimicrobials has been described as a cause of therapeutic failure which also has been related to a low interstitial concentration for hydrophilic antibiotics. In critically ill patients it may occur an accumulation of compartmental fluids which can be related to an increase in the distribution volume or changes in clearance of antimicrobials. Pharmacokinetic and pharmacodynamic parameters of antimicrobials are reviewed, which can be used as a tool to optimize the efficacy of antimicrobial therapy in order to avoid failures and resistance selection.

La neutropenia febril es una complicación grave de la terapia antineoplásica que se presenta más frecuentemente en pacientes con neoplasias hematológicas, asociada a tasas elevadas de mortalidad. Uno de los factores descritos como causa de fracasos terapéuticos de la terapia antimicrobiana es la inadecuada concentración tisular de los antimicrobianos que a su vez se correlaciona con bajas concentraciones en el líquido intersticial en el caso de los fármacos hidrofílicos. En pacientes críticamente enfermos se puede presentar acumulación compartimental de líquidos que a su vez se puede asociar con aumento en el volumen de distribución de los medicamentos o alteraciones en la depuración de los mismos. Se revisan los parámetros farmacocinéticos y farmacodinámicos de los antimicrobianos que pueden ser usados como herramienta para optimizar la eficacia de la terapia antiinfecciosa en busca de disminuir la tasa de fracasos y la selección de cepas resistentes.

[Pharmacokinetics and pharmacodynamics of antibacterial agents: on account of febrile neutropenic patients]. / Farmacocinética y farmacodinamia de antimicrobianos: a propósito de pacientes con neutropenia y fiebre.

Febrile neutropenia is a serious complication of antineoplastic therapy and it is more commonly found in hematologic patients, associated with high mortality rates. Inadequate tissue concentration of antimicrobials has been described as a cause of therapeutic failure which also has been related to a low interstitial concentration for hydrophilic antibiotics. In critically ill patients it may occur an accumulation of compartmental fluids which can be related to an increase in the distribution volume or changes in clearance of antimicrobials. Pharmacokinetic and pharmacodynamic parameters of antimicrobials are reviewed, which can be used as a tool to optimize the efficacy of antimicrobial therapy in order to avoid failures and resistance selection.