Emergence of Clonally-Related South Asian Clade I Clinical Isolates of Candida auris in a Greek COVID-19 Intensive Care Unit.

Candida auris has recently emerged as a multidrug-resistant yeast implicated in various healthcare-associated invasive infections and hospital outbreaks. In the current study, we report the first five intensive care unit (ICU) cases affected by C. auris isolates in Greece, during October 2020-January 2022. The ICU of the hospital was converted to a COVID-19 unit on 25 February 2021, during the third wave of COVID-19 in Greece. Identification of the isolates was confirmed by Matrix Assisted Laser Desorption Ionization Time of Flight mass spectroscopy (MALDI-TOF]. Antifungal susceptibility testing was performed by the EUCAST broth microdilution method. Based on the tentative CDC MIC breakpoints, all five C. auris isolates were resistant to fluconazole (≥32 µg/mL), while three of them exhibited resistance to amphotericin B (≥2 µg/mL). The environmental screening also revealed the dissemination of C. auris in the ICU. Molecular characterization of C. auris clinical and environmental isolates was performed by MultiLocus Sequence Typing (MLST) of a set of four genetic loci, namely ITS, D1/D2, RPB1 and RPB2, encoding for the internal transcribed spacer region (ITS) of the ribosomal subunit, the large ribosomal subunit region and the RNA polymerase II largest subunit, respectively. MLST analysis showed that all isolates possessed identical sequences in the four genetic loci and clustered with the South Asian clade I strains. Additionally, PCR amplification and sequencing of the CJJ09_001802 genetic locus, encoding for the "nucleolar protein 58" that contains clade-specific repeats was performed. Sanger sequence analysis of the TCCTTCTTC repeats within CJJ09_001802 locus also assigned the C. auris isolates to the South Asian clade I. Our study confirms that C. auris is an emerging yeast pathogen in our region, especially in the setting of the ongoing COVID-19 worldwide pandemic. Adherence to strict infection control is needed to restrain further spread of the pathogen.

Possible COVID-19-Associated Pulmonary Aspergillosis Due to Aspergillus niger in Greece.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes direct damage to the pulmonary epithelium, enabling Aspergillus invasion. Rapid progression and high mortality of invasive aspergillosis have been reported. In the present study, we report a rare case of possible COVID-19-associated pulmonary aspergillosis (CAPA) caused by A. niger in a Greek patient. Diagnosis was based on ECMM/ISHAM specific criteria and the new algorithm "BM-AspICU" for the invasive pulmonary aspergillosis diagnostic strategy. The fungal isolate was recovered in a non-bronchoalveolar lavage (non-BAL) sample and its identification was performed by standard macroscopic and microscopic morphological studies. MALDI-TOF analysis confirmed the identification of A. niger. In addition, galactomannan antigen and Aspergillus real-time PCR testing were positive in the non-BAL sample, while in serum they proved negative. The A. niger isolate showed an MIC for fluconazole ≥128 µg/mL, for itraconazole and posaconazole 0.25 µg/mL, for voriconazole 0.5 µg/mL, for flucytosine 4 µg/mL, for amphotericin B 1 µg/mL, and for all echinocandins (caspofungin, anidulafungin, micafungin) >8 µg/mL. The patient was initially treated with voriconazole; amphotericin B was subsequently added, when a significant progression of cavitation was demonstrated on chest computed tomography. A. niger was not isolated in subsequent samples and the patient's unfavorable outcome was attributed to septic shock caused by a pandrug-resistant Acinetobacter baumannii strain.

De-escalation of antimicrobial therapy in ICU settings with high prevalence of multidrug-resistant bacteria: a multicentre prospective observational cohort study in patients with sepsis or septic shock.

BACKGROUND: De-escalation of empirical antimicrobial therapy, a key component of antibiotic stewardship, is considered difficult in ICUs with high rates of antimicrobial resistance. OBJECTIVES: To assess the feasibility and the impact of antimicrobial de-escalation in ICUs with high rates of antimicrobial resistance. METHODS: Multicentre, prospective, observational study in septic patients with documented infections. Patients in whom de-escalation was applied were compared with patients without de-escalation by the use of a propensity score matching by SOFA score on the day of de-escalation initiation. RESULTS: A total of 262 patients (mean age 62.2 ± 15.1 years) were included. Antibiotic-resistant pathogens comprised 62.9%, classified as MDR (12.5%), extensively drug-resistant (49%) and pandrug-resistant (1.2%). In 97 (37%) patients de-escalation was judged not feasible in view of the antibiotic susceptibility results. Of the remaining 165 patients, judged as patients with de-escalation possibility, de-escalation was applied in 60 (22.9%). These were matched to an equal number of patients without de-escalation. In this subset of 120 patients, de-escalation compared with no de-escalation was associated with lower all-cause 28 day mortality (13.3% versus 36.7%, OR 0.27, 95% CI 0.11-0.66, P = 0.006); ICU and hospital mortality were also lower. De-escalation was associated with a subsequent collateral decrease in the SOFA score. Cox multivariate regression analysis revealed de-escalation as a significant factor for 28 day survival (HR 0.31, 95% CI 0.14-0.70, P = 0.005). CONCLUSIONS: In ICUs with high levels of antimicrobial resistance, feasibility of antimicrobial de-escalation was limited because of the multi-resistant pathogens isolated. However, when de-escalation was feasible and applied, it was associated with lower mortality.

Characteristics of superinfections during treatment with tigecycline.

Tigecycline has a broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant (MDR) strains. However, some Gram-negative bacteria are intrinsically resistant or have reduced susceptibility to tigecycline. We performed a prospective, observational study of 43 patients who received tigecycline as the treatment for serious infections due to MDR Gram-negative microorganisms, to evaluate superinfections. In 60.5% of our patients, tigecycline-resistant (T-R) Gram-negative microorganisms were isolated, representing superinfection in 37.2% and colonization in 23.5%. Pseudomonas aeruginosa was the predominant pathogen (48.4%) followed by Providencia stuartii, Proteus mirabilis and Stenotrophomonas maltophilia. Median time elapsed between tigecycline prescription and isolation of T-R pathogens was 7 days. The 16 superinfections consisted of ventilator-associated pneumonias (43.75%), catheter-related bloodstream infections (37.5%), intra-abdominal infections (12.5%) and urinary tract infection (6.25%). Attributed mortality to superinfections was 31.25%. The comparison of various potential risk factors for isolation of T-R microorganisms did not reveal statistically significant results.