Role of source control in critically ill candidemic patients: a multicenter retrospective study.

PURPOSE: Candidemia is associated with high mortality especially in critically ill patients. Our aim was to identify predictors of mortality among critically ill patients with candidemia with a focus on early interventions that can improve prognosis. METHODS: Multicenter retrospective study. SETTING: This retrospective study was conducted in Intensive Care Units from three European university hospitals from 2015 to 2021. Adult patients with at least one positive blood culture for Candida spp. were included. Patients who did not require source control were excluded. Primary outcome was 14-day mortality. RESULTS: A total of 409 episodes of candidemia were included. Most candidemias were catheter related (173; 41%), followed by unknown origin (170; 40%). Septic shock developed in 43% episodes. Overall, 14-day mortality rate was 29%. In Cox proportional hazards regression model, septic shock (P 0.001; HR 2.20, CI 1.38-3.50), SOFA score ≥ 10 points (P 0.008; HR 1.83, CI 1.18-2.86), and prior SARS-CoV-2 infection (P 0.003; HR 1.87, CI 1.23-2.85) were associated with 14-day mortality, while combined early appropriate antifungal treatment and source control (P < 0.001; HR 0.15, CI 0.08-0.28), and early source control without appropriate antifungal treatment (P < 0.001; HR 0.23, CI 0.12-0.47) were associated with better survival compared to those without neither early appropriate antifungal treatment nor source control. CONCLUSION: Early source control was associated with better outcome among candidemic critically ill patients.

Emergence of a mupirocin-resistant, methicillin-susceptible Staphylococcus aureus clone associated with skin and soft tissue infections in Greece.

BACKGROUND: Staphylococcus aureus causes various infections, including skin and soft tissue infections (SSTIs). In this study, methicillin-susceptible S. aureus (MSSA) from SSTIs among patients in three tertiary-care hospitals in Greece were studied in terms of antimicrobial resistance, clonal distribution, toxin and adhesin genes carriage. RESULTS: During a five-year period (2014-2018), 6145 S. aureus were recovered from 13,244 patients with SSTIs and tested for antimicrobial susceptibility. MSSA were 4806 (78.21 %) including 1484 isolates with mupirocin minimum inhibitory concentration (MIC) > 64 mg/L (30.88 %). Two hundred and sixty representative mupirocin-resistant MSSA were analyzed for genes encoding Panton-Valentine leukocidin (PVL, lukS/lukF-PV), exfoliative toxins (eta, etb), adhesin FnbA (fnbA) and resistance genes mupA (high-level resistance to mupirocin), fusB (fusidic acid), aminoglycosides' modifying enzymes, ermA, ermC and msrA (macrolides/lincosamides) by PCRs. Strains were classified into clones by PFGE and MLST. All mupirocin-resistant MSSA were penicillin-resistant; 92.7 % expressed resistance to fusidic acid and 88.9 % to tobramycin. All 260 molecularly analyzed isolates were mupA-positive; all fusidic acid-resistant (241/260) carried fusB whereas, the tobramycin-resistant ones (230), ant(4')-Ia. The majority carried eta (93.85 %), etb (98.08 %) and fnbA (88.85 %). PFGE typing revealed a mostly unvarying population; 260 MSSA were grouped into three types. One major eta/etb-positive clone comprising of 258/260 strains (99.2 %), PFGE type 1, was classified as ST121, including nine strains co-carrying PVL. Another PVL-positive strain was identified as ST1, and one toxins-negative as ST21. CONCLUSIONS: A mupirocin-resistant MSSA clone, ST121, carrying resistance, exfoliative toxins and adhesin genes, was spread and predominated in SSTIs from patients in Greece during the five-year studied period.

Fatality of Staphylococcus aureus infections in a Greek university hospital: role of inappropriate empiric treatment, methicillin resistance, and toxin genes' presence.

The aim of the present study was to identify predictors of fatality among patients with S. aureus infections requiring hospitalization. Cases hospitalized with S. aureus infections at the University General Hospital of Patras, Greece, during a 4-year period (2013-2016) were studied. mecA, lukS/lukF-PV (Panton-Valentine leukocidin, PVL), tst (toxic shock syndrome toxin), fnbA (fibronectin-binding protein A), eta, and etb (epidermolytic toxins) genes' carriage was detected by PCR in 149 selected patients. Among 464 patients, 346 were included (118 with missing data). Primary bacteremia predominated (44.2%), followed by lower respiratory tract infections (13.6%), deep seated infections (9.8%), osteoarticular (9.5%), and catheter-related bloodstream infections (6.1%). Methicillin-resistant S. aureus (MRSA) represented 33.8% of infections and were less likely to receive appropriate empiric treatment (79.5% versus 97.4%; P < 0.001). Thirty-day fatality was 14.5%. Multivariate analysis revealed that development of septic shock, Charlson Comorbidity Index, lower respiratory tract infection, bacteremia (primary or secondary), MRSA, and CRP was significantly associated with fatality. Appropriate empiric treatment was a predictor of good prognosis. Thirty-two out of 149 S. aureus (21.5%) carried lukS/lukF-PV genes, whereas, 14 (9.4%), 133 (78.7%), four (2.7%), and one (0.7%) carried tst, fnbA, eta, and etb genes, respectively. No difference was found among toxin genes' presence and mortality. PVL was significantly more frequently found among MRSA as compared to MSSA (45.1% versus 9.2%; P < 0.001). MRSA represented one third of the infections requiring hospitalization and were independently associated with fatality, probably since were more likely to receive inappropriate antibiotic treatment as compared to MSSA.

Molecular characteristics and predictors of mortality among Gram-positive bacteria isolated from bloodstream infections in critically ill patients during a 5-year period (2012-2016).

To identify the molecular characteristics of Gram-positive cocci isolated from blood cultures and clinical outcome among critically ill patients. This retrospective study was conducted in the general intensive care unit of the University General Hospital of Patras, Greece, during a 5-year period (2012-2016). All adult patients with a Gram-positive BSI were included. PCR was applied to identify mecA gene (staphylococci); vanA, vanB, and vanC genes (enterococci). Linezolid-resistant S. epidermidis, MRSA, and VRE were further typed by multilocus sequence typing. Mutations in region V of 23S rDNA and ribosomal protein L4were investigated by PCR and sequencing analysis. The presence of the cfr gene was tested by PCR. In total, 141 Gram-positive BSIs were included. Coagulase-negative staphylococci predominated (n = 69; 65 methicillin-resistant, 23 linezolid-resistant carrying both C2534T and T2504A mutations and belonging to the ST22 clone), followed by enterococci (n = 46; 11 vancomycin-resistant carrying vanA gene, classified into four clones), S. aureus (n = 22; 10 methicillin-resistant, classified into three clones) and streptococci (n = 4). The most common type of infection was catheter-related (66; 46.8%), followed by primary BSI (28; 19.9%). Overall 14-day fatality was 24.8%. Multivariate analysis revealed septic shock as independent predictor of fatality, while appropriate empiric antimicrobial treatment and catheter-related BSI were identified as a predictor of good prognosis. Even though most of Gram-positive cocci were multidrug-resistant, fatality rate was low, associated with catheter-related BSIs. Among CNS, LR isolates represented one-third of BSIs due to the dissemination of ST22 S. epidermidis propagated by utilization of linezolid.

Increasing incidence of candidaemia and shifting epidemiology in favor of Candida non-albicans in a 9-year period (2009-2017) in a university Greek hospital.

PURPOSE: The aim of the present study was to analyze candidaemia's epidemiology (incidence, species distribution, and susceptibility rates) and antifungal consumption during a 9-year period. METHODS: All candidaemias recorded at The University General Hospital of Patras, Greece, between 2009 and 2017 were included. Candida isolates were identified using the germ tube test, API 20C AUX System, and/or Vitek-2 YST card. Antifungal susceptibility was determined by the gradient method according to CLSI. RESULTS: During the study period, 505 episodes of candidaemia were observed with an overall incidence of 1.5 episodes per 1000 hospital admissions (1.1 episodes in 2009 to 1.9 in 2017: P 0.038, r 0.694). C. albicans was the leading cause (200 cases; 39.6%), followed by C. parapsilosis (185; 36.6%), C. glabrata (56; 11.1%), C. tropicalis (50; 9.9%), C. krusei (8; 0.2%), C. lusitaniae (5; < 0.1%), and C. guilliermondii (1; < 0.1%). Overall resistance to fluconazole, voriconazole, anidulafungin, caspofungin, and micafungin (according to CLSI) were 11.6%, 4.1%, 2.0%, 6.0%, and 0.8%, respectively. The overall consumption of antifungal drugs was stable, with a significant reduction of fluconazole's use in favor of echinocandins. CONCLUSIONS: An increase in the incidence of candidaemia and a predominance of Candida non-albicans due to decreasing use of fluconazole in favor of more potent antifungals, such as echinocandins, are reported in this study.

Trends of Bloodstream Infections in a University Greek Hospital during a Three-Year Period: Incidence of Multidrug-Resistant Bacteria and Seasonality in Gram-negative Predominance.

The aim of the study was to assess the epidemiology, the incidence of multidrug-resistant bacteria and bloodstream infections' (BSIs) seasonality in a university hospital. This retrospective study was carried out in the University General Hospital of Patras, Greece, during 2011-13 y. Blood cultures from patients with clinical presentation suggestive of bloodstream infection were performed by the BacT/ALERT System. Isolates were identified by Vitek 2 Advanced Expert System. Antibiotic susceptibility testing was performed by the disk diffusion method and E-test. Resistance genes (mecA in staphylococci; vanA/vanB/vanC in enterococci; blaKPC/blaVIM/blaNDM in Klebsiella spp.) were detected by PCR. In total, 4607 (9.7%) blood cultures were positive from 47451 sets sent to Department of Microbiology, representing 1732 BSIs. Gram-negative bacteria (52.3%) were the most commonly isolated, followed by Gram-positive (39.5%), fungi (6.6%) and anaerobes bacteria (1.8%). The highest contamination rate was observed among Gram-positive bacteria (42.3%). Among 330 CNS and 150 Staphylococcus aureus, 281 (85.2%) and 60 (40.0%) were mecA-positive, respectively. From 113 enterococci, eight were vanA, two vanB and two vanC-positives. Of the total 207 carbapenem-resistant Klebsiella pneumoniae (73.4%), 202 carried blaKPC, four blaKPC and blaVIM and one blaVIM. A significant increase in monthly BSIs' incidence was shown (R2: 0.449), which may be attributed to a rise of Gram-positive BSIs (R2: 0.337). Gram-positive BSIs were less frequent in spring (P < 0.001), summer (P < 0.001), and autumn (P < 0.001), as compared to winter months, while Gram-negative bacteria (P < 0.001) and fungi (P < 0.001) were more frequent in summer months. BSIs due to methicillin resistant S. aureus and carbapenem-resistant Gram-negative bacteria increased during the study period. The increasing incidence of BSIs can be attributed to an increase of Gram-positive BSI incidence, even though Gram-negative bacteria remained the predominant ones. Seasonality may play a role in the predominance of Gram-negative's BSI.

Daptomycin Liposomes Exhibit Enhanced Activity against Staphylococci Biofilms Compared to Free Drug.

The purpose of the present study was to investigate the anti-staphylococcal activity of liposomal daptomycin against four biofilm-producing S. aureus and S. epidermidis clinical strains, three of which are methicillin-resistant. Neutral and negatively charged daptomycin-loaded liposomes were prepared using three methods, namely, thin-film hydration (TFH), a dehydration-rehydration vesicle (DRV) method, and microfluidic mixing (MM); moreover, they were characterized for drug encapsulation (EE%), size distribution, zeta-potential, vesicle stability, drug release, and drug integrity. Interestingly, whilst drug loading in THF and DRV nanosized (by extrusion) vesicles was around 30-35, very low loading (~4%) was possible in MM vesicles, requiring further explanatory investigations. Liposomal encapsulation protected daptomycin from degradation and preserved its bioactivity. Biofilm mass (crystal violet, CV), biofilm viability (MTT), and growth curve (GC) assays evaluated the antimicrobial activity of neutral and negatively charged daptomycin-liposomes towards planktonic bacteria and biofilms. Neutral liposomes exhibited dramatically enhanced inhibition of bacterial growth (compared to the free drug) for all species studied, while negatively charged liposomes were totally inactive. Biofilm prevention and treatment studies revealed high antibiofilm activity of liposomal daptomycin. Neutral liposomes were more active for prevention and negative charge ones for treating established biofilms. Planktonic bacteria as well as the matured biofilms of low daptomycin-susceptible, methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) strains were almost completely eradicated by liposomal-daptomycin, indicating the need for their further exploration as antimicrobial therapeutics.

Incidence of Carbapenem-Resistant Gram-Negative Bacterial Infections in Critically Ill Patients with COVID-19 as Compared to Non-COVID-19 Patients: A Prospective Case-Control Study.

Introduction: Critically ill COVID-19 patients hospitalized in intensive care units (ICU) are immunosuppressed due to SARSCoV-2-related immunological effects and are administered immunomodulatory drugs. This study aimed to determine whether these patients carry an increased risk of multi-drug resistant (MDR) and especially carbapenem-resistant Gram-negative (CRGN) bacterial infections compared to other critically ill patients without COVID-19. Materials and Methods: A prospective case-control study was conducted between January 2022 and August 2023. The ICU patients were divided into two groups (COVID-19 and non-COVID-19). Differences in the incidence of CRGN infections from Klebsiella pneumoniae, Acinetobacter spp., and Pseudomonas aeruginosa were investigated. In addition, an indicator of the infection rate of the patients during their ICU stay was calculated. Factors independently related to mortality risk were studied. Results: Forty-two COVID-19 and 36 non-COVID-19 patients were analyzed. There was no statistically significant difference in the incidence of CRGN between COVID-19 and non-COVID-19 patients. The infection rate was similar in the two groups. Regarding the aetiological agents of CRGN infections, Pseudomonas aeruginosa was significantly more common in non-COVID-19 patients (p=0.007). COVID-19 patients had longer hospitalisation before ICU admission (p=0.003) and shorter ICU length of stay (LOS) (p=0.005). ICU COVID-19 patients had significantly higher mortality (p < 0.001) and sequential organ failure assessment (SOFA) score (p < 0.001) compared to non-COVID-19 patients. Μortality secondary to CRGN infections was also higher in COVID-19 patients compared to non-COVID-19 patients (p=0.033). Male gender, age, ICU LOS, and hospital LOS before ICU admission were independent risk factors for developing CRGN infections. Independent risk factors for patients' mortality were COVID-19 infection, obesity, SOFA score, total number of comorbidities, WBC count, and CRP, but not infection from CRGN pathogens. Conclusions: The incidence of CRGN infections in critically ill COVID-19 patients is not different from that of non-COVID-19 ICU patients. The higher mortality of COVID-19 patients in the ICU is associated with higher disease severity scores, a higher incidence of obesity, and multiple underlying comorbidities, but not with CRGN infections.

Efficacy of Fosfomycin-Containing Regimens for Treatment of Bacteremia Due to Pan-Drug Resistant Acinetobacter baumannii in Critically Ill Patients: A Case Series Study.

Acinetobacter baumannii (AB) has evolved over the last decades as a major problem in carbapenem-resistant gram-negative nosocomial infections, associated with high mortality rates especially in the intensive care unit (ICU). Recent reports highlight the increasing prevalence of resistance to colistin, a last resort therapeutic option for carbapenem-resistant AB. We retrospectively evaluated the characteristics, treatment regimens and outcomes of twenty patients with pan-drug resistant (PDR) AB primary bacteremia hospitalized in the ICU of the University General Hospital of Patras, during a two-year period (October 2020-September 2022). The 28-day mortality reached 50%. Between survivors and non-survivors, no differences were found regarding age, gender, and Charlson comorbidity index (CCI). However, non-survivors had higher APACHE II scores and higher prevalence of septic shock and COVID-19 infection. A significantly higher percentage in the survivor group received Fosfomycin as part of the combination regimen. Inclusion of fosfomycin in the combination therapeutic regimen was associated with significantly better survival as compared to non-fosfomycin-containing regimens. In view of the increasing prevalence of PDR-AB infections in ICUs, its associated high rates of mortality and the lack of effective treatment options, the observed survival benefit with fosfomycin inclusion in the therapeutic regimen merits further validation in larger prospective studies.

Acid-fast bacteria as causative agents of skin and soft tissue infections: case presentations and literature review.

Acid-fast bacteria can be implicated in skin and soft tissue infections. Diagnostic identification can be challenging or not feasible by routine laboratory techniques, especially if there is no access to the Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) technology. Here, we present two cases of skin and soft tissue infections caused by two different acid-fast bacteria, Nocardia brasiliensis and Mycobacterium marinum. They both grew on Löwenstein-Jensen medium, Sabouraud agar medium and blood agar medium. Both bacteria appeared acid-fast by Ziehl-Neelsen stain and Gram-positive by Gram stain. The identification was performed by MALDI-TOF MS and gene analysis. N. brasiliensis and nontuberculous mycobacterium M. marinum represent rare pathogens that cause severe skin and soft tissue infections. Failure to identify the causative agent and subsequent inappropriate or inadequate treatment may lead to severe complications or even disseminated disease, especially in immunocompromised individuals.

Fungemia due to rare non-Candida yeasts between 2018 and 2021 in a Greek tertiary care university hospital.

INTRODUCTION: Non-Candida yeasts, although rare, are increasingly encountered and recognized as a growing threat. METHODS: Cases of bloodstream infections (BSIs) due to non-Candida yeasts (NCYs) during the last four years (2018-2021) are presented. RESULTS: During the study period, 16 cases caused by non-Candida yeasts out of 400 cases of yeast BSIs were recorded, corresponding to an incidence of 4%. Yeasts that were isolated included Cryptococcus spp (4 isolates-25%), Rhodotorula mucilaginosa (2 isolates-12.5%), Trichosporon asahii (7 isolates-43.75%) and Saccharomyces cerevisiae (3 isolates-18.75%). Predisposing factors involved mostly hematological malignancies, long term hospitalization or major surgical interventions. Most isolates, 15 out of 16 were susceptible to amphotericin B. Voriconazole was the most active azole in vitro. All isolates, except Saccharomyces spp., were resistant to echinocandins. DISCUSSION: Early recognition of rare yeasts as causative agents of BSIs and prompt initiation of appropriate treatment based on current guidelines and expertise remain crucial in efficient patient management.

Laboratory Surveillance of Acinetobacter spp. Bloodstream Infections in a Tertiary University Hospital during a 9-Year Period.

Multidrug-resistant Acinetobacter baumannii infections have become a threat for public health worldwide. The aim of the present study was to follow-up resistance patterns of Acinetobacter spp. bloodstream isolates in a Tertiary University Hospital over the last nine years, from 2014 to 2022. Susceptibility patterns were followed for the following antimicrobial agents: amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, imipenem, meropenem, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Minimal inhibitory concentration (MIC) values to ampicillin/sulbactam, cefepime, ceftazidime, minocycline, piperacillin/tazobactam were evaluated from 2020 to 2023. During the study period, 853 Acinetobacter spp. bloodstream infections (BSIs) were recorded, accounting for 5.36% of all BSIs. A. baumannii was isolated in 795 cases (93.2%), during the study period. Most BSIs were recorded in adult intensive care units (ICU) (46.2%) and medical wards (42%). Among A. baumannii isolates, 4.5% were multidrug-resistant, 84.7% were extensively drug-resistant, and 8.5% were pandrug-resistant. Resistance to carbapenems was over 95%. Resistance to tigecycline increased significantly during the last years of the study (2020-2022); A. baumannii isolates with MIC ≤ 2 µg/mL accounted for 28.5% of all isolates. Resistance to colistin exhibited an increasing pattern up to 42.2% in 2022. Increasing resistance rates and the evolution of pandrug-resistant isolates call for the urgent application of preventive and response actions.

Association of the Bacteria of the Vermiform Appendix and the Peritoneal Cavity with Complicated Acute Appendicitis in Children.

BACKGROUND: Primary infection has been questioned as the pathogenetic cause of acute appendicitis. We attempted to identify the bacteria involved and to investigate if their species, types, or combinations affected the severity of acute appendicitis in children. METHODS: Samples from both the appendiceal lumen and the peritoneal cavity of 72 children who underwent appendectomy were collected to perform bacterial culture analysis. The outcomes were studied to identify if and how they were associated with the severity of the disease. Regression analysis was performed to identify any risk factors associated with complicated appendicitis. RESULTS: Escherichia coli, Pseudomonas aeruginosa, and Streptococcus species were the most common pathogens found in the study population. The same microorganisms, either combined or separate, were the most common in the appendiceal lumen and the peritoneal cavity of patients with complicated appendicitis. Gram-negative bacteria and polymicrobial cultures in the peritoneal fluid and in the appendiceal lumen were associated with complicated appendicitis. Polymicrobial cultures in the peritoneal cavity presented a four times higher risk of complicated appendicitis. CONCLUSIONS: Polymicrobial presentation and Gram-negative bacteria are associated with complicated appendicitis. Antibiotic regimens should target the combinations of the most frequently identified pathogens, speculating the value of early antipseudomonal intervention.

An extracellular Staphylococcus epidermidis polysaccharide: relation to Polysaccharide Intercellular Adhesin and its implication in phagocytosis.

BACKGROUND: The skin commensal and opportunistic pathogen Staphylococcus epidermidis is a leading cause of hospital-acquired and biomaterial-associated infections. The polysaccharide intercellular adhesin (PIA), a homoglycan composed of ß-1,6-linked N-acetylglucosamine residues, synthesized by enzymes encoded in icaADBC is a major functional factor in biofilm accumulation, promoting virulence in experimental biomaterial-associated S. epidermidis infection. Extracellular mucous layer extracts of S. epidermidis contain another major polysaccharide, referred to as 20-kDa polysaccharide (20-kDaPS), composed mainly out of glucose, N-acetylglucosamine, and being partially sulfated. 20-kDaPS antiserum prevents adhesion of S. epidermidis on endothelial cells and development of experimental keratitis in rabbits. Here we provide experimental evidence that 20-kDaPS and PIA represent distinct molecules and that 20-kDaPS is implicated in endocytosis of S. epidermidis bacterial cells by human monocyte-derived macrophages. RESULTS: Analysis of 75 clinical coagulase-negative staphylococci from blood-cultures and central venous catheter tips indicated that 20-kDaPS is expressed exclusively in S. epidermidis but not in other coagulase-negative staphylococcal species. Tn917-insertion in various locations in icaADBC in mutants M10, M22, M23, and M24 of S. epidermidis 1457 are abolished for PIA synthesis, while 20-kDaPS expression appears unaltered as compared to wild-type strains using specific anti-PIA and anti-20-kDaPS antisera. While periodate oxidation and dispersin B treatments abolish immuno-reactivity and intercellular adhesive properties of PIA, no abrogative activity is exerted towards 20-kDaPS immunochemical reactivity following these treatments. PIA polysaccharide I-containing fractions eluting from Q-Sepharose were devoid of detectable 20-kDaPS using specific ELISA. Preincubation of non-20-kDaPS-producing clinical strain with increasing amounts of 20-kDaPS inhibits endocytosis by human macrophages, whereas, preincubation of 20-kDaPS-producing strain ATCC35983 with 20-kDaPS antiserum enhances bacterial endocytosis by human macrophages. CONCLUSIONS: In conclusion, icaADBC is not involved in 20-kDaPS synthesis, while the chemical and chromatographic properties of PIA and 20-kDaPS are distinct. 20-kDaPS exhibits anti-phagocytic properties, whereas, 20-kDaPS antiserum may have a beneficial effect on combating infection by 20-kDaPS-producing S. epidermidis.

Clonal dissemination and resistance genes among Stenotrophomonas maltophilia in a Greek University Hospital during a four-year period.

Treatment of Stenotrophomonas maltophilia infections comprises of sulfamethoxazole/tripethoprim (SXT) or fluoroquinolones. We investigated antimicrobial resistance, presence of resistance genes (sul1, smqnr) and clonal dissemination in S. maltophilia from a university hospital. Among 62 isolates, 45 (73%) represented infection. Two isolates (3%) were resistant to SXT and three (5%) to levofloxacin. Twenty-nine isolates (47%), including two out of three levofloxacin-resistant, carried smqnr. Resistance of S. maltophilia was low and was not associated with sul1 or smqnr carriage. Although high degree of genetic diversity was identified (29 pulsotypes), 22/62 (35.5%) strains were classified into four clones; clone b was associated with bacteraemias.

Invasive Candida kefyr infection presenting as pyelonephritis in an ICU hospitalized COVID-19 patient: Case report and review of the literature.

Candida kefyr (Kluyveromyces marxianus), an ascomycetous environmental yeast, occasionally isolated from dairy products, represents an uncommon but emerging pathogen in immunocompromised patients. Herein, we present a case of C. kefyr pyelonephritis in a 41-year-old, previously immunocompetent, patient who was hospitalized in an COVID-19 ICU. Pyelonephritis was associated with caliectasis and obstruction due to possible fungus ball formation. Predisposing factors included ICU stay, use of broad spectrum antibiotics and steroids, central venous catheterization, mechanical ventilation and urologic manipulation. Susceptibility testing revealed high MIC values to amphotericin B. Infection was effectively controlled by prolonged administration of fluconazole without further surgical intervention. COVID-19 complicated with invasive candidiasis is an increasingly observed clinical situation that warrants high suspicion index and careful evaluation of laboratory data.

A Seven-Year Microbiological and Molecular Study of Bacteremias Due to Carbapenemase-Producing Klebsiella Pneumoniae: An Interrupted Time-Series Analysis of Changes in the Carbapenemase Gene's Distribution after Introduction of Ceftazidime/Avibactam.

Background: Ceftazidime/avibactam (CZA) is a new option for the treatment of KPC-producing Klebsiella pneumoniae. The aim of this study was to determine resistance patterns and carbapenemase genes among K. pneumoniae (CP-Kp) bacteremic isolates before and after CZA introduction. Methods: K. pneumoniae from blood cultures of patients being treated in a Greek university hospital during 2015−21 were included. PCR for blaKPC, blaVIM, blaNDM and blaOXA-48 genes was performed. Results: Among 912 K. pneumoniae bacteremias: 725 (79.5%) were due to carbapenemase-producing isolates; 488 (67.3%) carried blaKPC; 108 (14.9%) blaVIM; 100 (13.8%) blaNDM; and 29 (4%) carried a combination of blaKPC, blaVIM or blaNDM. The incidence of CP-Kp bacteremias was 59 per 100,000 patient-days. The incidence of CP-Kp changed from a downward pre-CZA trend to an upward trend in the CZA period (p = 0.007). BSIs due to KPC-producing isolates showed a continuous downward trend in the pre-CZA and CZA periods (p = 0.067), while BSIs due to isolates carrying blaVIM or blaNDM changed from a downward trend in the pre-CZA to an upward trend in the CZA period (p < 0.001). Conclusions: An abrupt change in the epidemiology of CP-Kp was observed in 2018, due to the re-emergence of VIM-producing isolates after the suppression of KPC-producing ones via the use of CZA.

Increased incidence of candidemia in critically ill patients during the Coronavirus Disease 2019 (COVID-19) pandemic.

BACKGROUND: Patients with severe Coronavirus Disease 2019 (COVID-19) are treated with corticosteroids. AIM: We aimed to evaluate the role of corticosteroid treatment in candidemia development during the COVID-19 pandemic. METHODS: This retrospective study was conducted in a Greek ICU, from 2010 to August 2021, encompassing a pre-pandemic and a pandemic period (pandemic period: April 2020 to August 2021). All adult patients with candidemia were included. RESULTS: During the study period, 3,572 patients were admitted to the ICU, 339 patients during the pandemic period, of whom 196 were SARS-CoV-2-positive. In total, 281 candidemia episodes were observed in 239 patients, 114 in the pandemic period. The majority of candidemias in both periods were catheter-related (161; 50.4%). The incidence of candidemia in the pre-pandemic period was 5.2 episodes per 100 admissions, while in the pandemic period was 33.6 (p < 0.001). In the pandemic period, the incidence among COVID-19 patients was 38.8 episodes per 100 admissions, while in patients without COVID-19 incidence was 26.6 (p = 0.019). Corticosteroid administration in both periods was not associated with increased candidemia incidence. CONCLUSIONS: A significant increase of candidemia incidence was observed during the pandemic period in patients with and without COVID-19. This increase cannot be solely attributed to immunosuppression (corticosteroids, tocilizumab) of severe COVID-19 patients, but also to increased workload of medical and nursing staff.

Moxifloxacin Liposomes: Effect of Liposome Preparation Method on Physicochemical Properties and Antimicrobial Activity against Staphylococcus epidermidis.

The aim of this study was the development of optimal sustained-release moxifloxacin (MOX)-loaded liposomes as intraocular therapeutics of endophthalmitis. Two methods were compared for the preparation of MOX liposomes; the dehydration-rehydration (DRV) method and the active loading method (AL). Numerous lipid-membrane compositions were studied to determine the potential effect on MOX loading and retention in liposomes. MOX and phospholipid contents were measured by HPLC and a colorimetric assay for phospholipids, respectively. Vesicle size distribution and surface charge were measured by DLS, and morphology was evaluated by cryo-TEM. The AL method conferred liposomes with higher MOX encapsulation compared to the DRV method for all the lipid compositions used. Cryo-TEM showed that both liposome types had round vesicular structure and size around 100-150 nm, while a granular texture was evident in the entrapped aqueous compartments of most AL liposomes, but substantially less in DRV liposomes; X-ray diffraction analysis demonstrated slight crystallinity in AL liposomes, especially the ones with highest MOX encapsulation. AL liposomes retained MOX for significantly longer time periods compared to DRVs. Lipid composition did not affect MOX release from DRV liposomes but significantly altered drug loading/release in AL liposomes. Interestingly, AL liposomes demonstrated substantially higher antimicrobial potential towards S. epidermidis growth and biofilm susceptibility compared to corresponding DRV liposomes, indicating the importance of MOX retention in liposomes on their activity. In conclusion, the liposome preparation method/type determines the rate of MOX release from liposomes and modulates their antimicrobial potential, a finding that deserves further in vitro and in vivo exploitation.