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.

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.

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.

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.

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.

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

ABSTRACT 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.

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.

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.

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.

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

Abstract 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.

In Vitro Anti-Biofilm Activity of Bacteriophage K (ATCC 19685-B1) and Daptomycin against Staphylococci.

The purpose of the present study was to investigate anti-staphylococcal activity of daptomycin and bacteriophage K, alone or in combination, against biofilm-producers and non-producers S. aureus and S. epidermidis strains, under biofilm forming and cells' proliferation conditions. Daptomycin and bacteriophage K (ATCC 19685B1), in different concentrations, were tested against 10 Staphylococcus aureus and 10 S. epidermidis, characterized by phenotypes and genotypes. The quantitative microtiter plate (crystal violet, CV), methylthiazoltetrazolium (MTT), and growth curve (GC) assays were performed. No statistically significant difference was found between species, whereas daptomycin alone performed better using medium and high concentrations of the drug and bacteriophage K was more active against strains with higher susceptibility, by CV and MTT assays. Best results were achieved using both agents combined in high concentrations. Bacteriophage K was effective within 3.8 and 2.4 h, depending on the concentration used, by the GC assay. Combination of daptomycin with bacteriophage K was more effective against staphylococci, depending on the concentrations used and strains' susceptibility. Further studies are needed to evaluate if this approach might be a choice for prevention or therapy of biofilm-associated infections.

In vitro activity of dalbavancin and other anti-staphylococcal agents against infecting isolates of methicillin-resistant coagulase-negative staphylococci.

Introduction. Dalbavancin was approved in Europe in 2015 for skin and soft tissue infections.Hypothesis/Gap Statement. Data on methicillin-resistant coagulase-negative staphylococci (MR-CNS) dalbavancin susceptibility are scarce.Aim. To assess the susceptibility of MR-CNS to dalbavancin and other anti-staphylococcal agents.Methodology. A total of 443 MR-CNS clinical isolates from patients hospitalized in a Greek university hospital during a 2.5-year period (January 2018 to June 2020) were included. The MICs for vancomycin, teicoplanin, linezolid and daptomycin were investigated by Etest and the MIC for dalbavancin was determined according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines in 196 isolates. The consumption of the aforementioned antimicrobials was calculated.Results. In total, 51 isolates were resistant to teicoplanin (11.5 %) and 211 (47.6 %) to linezolid; all were susceptible to vancomycin and daptomycin. Among 196 isolates tested, 32 (16.3 %) were resistant to dalbavancin. A significant increase of MIC during the study period was found for vancomycin, teicoplanin and daptomycin, while a decrease in linezolid's MIC was observed. Dalbavancin's MIC remained stable. No difference in consumption was observed among the studied anti-staphylococcal agents.Conclusion. An increase of vancomycin, teicoplanin and daptomycin MICs among MR-CNS was observed, whereas 47.6 % of isolates were non-susceptible to linezolid. Dalbavancin retains excellent potency against MR-CNS, even in the presence of non-susceptibility to other anti-staphylococcal antibiotics.

Risk factors for isolation of fluconazole and echinocandin non-susceptible Candida species in critically ill patients.

Introduction. Resistance rates to azoles and echinocandins of Candida spp. increased over the last decade.Hypothesis/Gap Statement. Widespread use of antifungals could lead to development and dissemination of resistant Candida spp.Aim. To identify risk factors for isolation of Candida spp. non-susceptible to either fluconazole or echinocandins.Methodology. All patients hospitalized in the Intensive Care Unit (ICU) of the University General Hospital of Patras, Greece with Candida spp. isolated from clinical specimens during a ten-year period (2010-19) were included. Candida isolates were identified using Vitek-2 YST card. Consumption of antifungals was calculated.Results. During the study period, 253 isolates were included. C. non-albicans predominated (64.4 %) with C. parapsilosis being the most commonly isolated (42.3 %) followed by C. glabrata (nomenclatural change to Nakaseomyces glabrataa; 8.7 %) and C. tropicalis (11.9 %). Among all isolates, 45.8 and 28.5 % were non-susceptible and resistant to fluconazole, respectively. Concerning echinocandins, 8.7 % of isolates were non-susceptible to at least one echinocandin (anidulafungin or micafungin) and 3.1 % resistant. Multivariate analysis revealed that hospitalization during 2015-19, as compared to 2010-14, isolate being non-albicans or non-susceptible to at least one echinocandin was associated with isolation of fluconazole non-susceptible isolate. Administration of echinocandin, isolate being C. glabrata or C. tropicalis, or Candida spp. non-susceptible to fluconazole were independently associated with isolation of Candida spp. non-susceptible to at least one echinocandin. Fluconazole's administration decreased during the study period, whereas liposomal-amphotericin B's and echinoncandins' administration remained stable.Conclusion. Fluconazole's non-susceptibility increased during the study period, despite the decrease of its administration. Although echinocandins' administration remained stable, non-susceptibility among Candida spp. increased.

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.

External validation of INCREMENT-CPE score in a retrospective cohort of carbapenemase-producing Klebsiella pneumoniae bloodstream infections in critically ill patients.

OBJECTIVES: Our aim was to validate the INCREMENT-CPE score (ICS) in patients hospitalized in the intensive care unit (ICU) with bacteraemia due to carbapenemase-producing Klebsiella pneumoniae (CP-Kp). METHODS: The study was conducted in the ICU of the University General Hospital of Patras, Greece, during a 10-year period (2010-2019). Patients with monomicrobial bacteraemia due to CP-Kp were included. Primary outcome was 14-day mortality. MICs of meropenem, tigecycline, fosfomycin and ceftazidime/avibactam were determined by Etest, whereas for colistin the broth microdilution method was applied. PCR for blaKPC, blaVIM, blaNDM and blaOXA genes was used. RESULTS: Among 384 CP-Kp bacteraemias, most were primary (166, 43.2%) followed by catheter-related (143, 37.2%). Most isolates carried blaKPC (318, 82.8%). Fourteen-day mortality was 26.3% (101 patients). ICS score was 11.1 ± 4.2. An ICS ≥10 showed a sensitivity of 98.0% and a negative predictive value of 98.7%. The area under the curve of ICS (0.800) was comparable to those of the Pitt bacteraemia score (0.799), the Simplified Acute Physiology Score II (SAPS II) (0.797) and the Sequential Organ Failure Assessment score (SOFA) (0.815). CONCLUSIONS: ICS showed predictive efficacy similar to that of the SAPS II, SOFA and Pitt bacteraemia scores.

Mortality of Pandrug-Resistant Klebsiella pneumoniae Bloodstream Infections in Critically Ill Patients: A Retrospective Cohort of 115 Episodes.

BACKGROUND: The increased frequency of bacteraemias caused by pandrug-resistant Klebsiella pneumoniae (PDR-Kp) has significant implications. The aim of the present study was to identify predictors associated with mortality of PDR-Kp bacteraemias. METHODS: Patients with monomicrobial bacteraemia due to PDR-Kp were included. K. pneumoniae was considered PDR if it showed resistance to all available groups of antibiotics. Primary outcome was 30-day mortality. Minimum inhibitory concentrations (MICs) of meropenem, tigecycline, fosfomycin, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. bla KPC, bla VIM, bla NDM, and bla OXA genes were detected by PCR. RESULTS: Among 115 PDR-Kp bacteraemias, the majority of infections were primary bacteraemias (53; 46.1%), followed by catheter-related (35; 30.4%). All isolates were resistant to tested antimicrobials. bla KPC was the most prevalent carbapenemase gene (98 isolates; 85.2%). Thirty-day mortality was 39.1%; among 51 patients with septic shock, 30-day mortality was 54.9%. Multivariate analysis identified the development of septic shock, Charlson comorbidity index, and bacteraemia other than primary or catheter-related as independent predictors of mortality, while a combination of at least three antimicrobials was identified as an independent predictor of survival. CONCLUSIONS: Mortality of PDR-Kp bloodstream infections was high. Administration of at least three antimicrobials might be beneficial for infections in critically ill patients caused by such pathogens.