New antimicrobial molecules effective against Pseudomonas aeruginosa, known as an antibiotic-resistant “high-priority pathogen”, are urgently required because of its ability to develop biofilms ...related to healthcare-acquired infections. In this study, for the first time, the anti-biofilm and anti-virulence activities of a polyphenolic extract of extra-virgin olive oil as well as purified oleocanthal and oleacein, toward P. aeruginosa clinical isolates were investigated. The main result of our study was the anti-virulence activity of the mixture of oleacein and oleocanthal toward multidrug-resistant and intermediately resistant strains of P. aeruginosa isolated from patients with ventilator-associated pneumonia or surgical site infection. Specifically, the mixture of oleacein (2.5 mM)/oleocanthal (2.5 mM) significantly inhibited biofilm formation, alginate and pyocyanin production, and motility in both P. aeruginosa strains (p < 0.05); scanning electron microscopy analysis further evidenced its ability to inhibit bacterial cell adhesion as well as the production of the extracellular matrix. In conclusion, our results suggest the potential application of the oleacein/oleocanthal mixture in the management of healthcare-associated P. aeruginosa infections, particularly in the era of increasing antimicrobial resistance.
In 2021,
Klebsiella pneumoniae
sequence type 307 (ST307) strains causing pulmonary and bloodstream infections identified in a hospital in Rome, Italy, reached high levels of resistance to ...ceftazidime-avibactam (CZA). One of these strains reached high levels of resistance to both CZA and carbapenems and carried two copies of
bla
KPC-3
and one copy of
bla
KPC-31
located on plasmid pKpQIL. The genomes and plasmids of CZA-resistant ST307 strains were analyzed to identify the molecular mechanisms leading to the evolution of resistance and compared with ST307 genomes at local and global levels. A complex pattern of multiple plasmids in rearranged configurations, coresident within the CZA-carbapenem–resistant
K. pneumoniae
strain, was observed. Characterization of these plasmids revealed recombination and segregation events explaining why
K. pneumoniae
isolates from the same patient had different antibiotic resistance profiles. This study illustrates the intense genetic plasticity occurring in ST307, one of the most worldwide-diffused
K. pneumoniae
high-risk clones.
In 2021, Klebsiella pneumoniae sequence type 307 (ST307) strains causing pulmonary and bloodstream infections identified in a hospital in Rome, Italy, reached high levels of resistance to ...ceftazidime-avibactam (CZA). One of these strains reached high levels of resistance to both CZA and carbapenems and carried two copies of
and one copy of
located on plasmid pKpQIL. The genomes and plasmids of CZA-resistant ST307 strains were analyzed to identify the molecular mechanisms leading to the evolution of resistance and compared with ST307 genomes at local and global levels. A complex pattern of multiple plasmids in rearranged configurations, coresident within the CZA-carbapenem-resistant K. pneumoniae strain, was observed. Characterization of these plasmids revealed recombination and segregation events explaining why K. pneumoniae isolates from the same patient had different antibiotic resistance profiles. This study illustrates the intense genetic plasticity occurring in ST307, one of the most worldwide-diffused K. pneumoniae high-risk clones.
Abstract
Background
Our aim was to analyze mortality attributable to carbapenem-resistant (CR) gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs).
Methods
Prospective ...multicentric study including patients with GNB-BSI from 19 Italian hospitals (June 2018–January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: Klebsiella pneumoniae carbapenemase (KPC)–producing Enterobacterales, metallo-β-lactamases (MBL)–producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aORs) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium.
Results
Overall, 1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (P < .001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72–12.76), CRPA (aOR 1.99, 95% CI 1.48–5.95) and CRAB (aOR 2.65, 95% CI 1.52–4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB.
Conclusions
In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.
Evaluation of mortality attributable to antimicrobial resistance is challenging. We calculated attributable mortality in bacteremia by different carbapenem-resistant gram-negative bacilli. Carbapenem resistance is associated with an excess mortality (highest in MBL-producing Enterobacterales) even if active antibiotic therapy is started early.
...we tried to reproduce the indeterminate results in the laboratory. Interpretation of these results remains controversial, since according to the interpretation offered by the GeneXpert Dx V.4.4 ...software these indeterminate results should be considered as negative. ...it appears that for a better characterisation of the diagnosis, such samples could be further analysed with other commercial platforms or by pulsed field gel electrophoresis (PFGE) assay. The findings of Jazmati et al showed a tight correlation between low CT values and worst course of CDI. 3 Leis et al found that 33% of patients with indeterminate RT-PCR results presented a positive culture for toxigenic C. difficile, indicating that these cases cannot be reported as negative, 2 in particular for those patients that received antibiotic treatment before faecal collection for C. difficile diagnosis, with consequent underestimation of CDI. 4 Moreover, Planche et al highlighted the importance of free toxin detection for severe prognosis of patients with CDI. 5 Therefore, in our opinion, several questions still need to be pointed out: is the low amount of toxin-encoding C. difficile DNA the hallmark of the bacterial cells still alive in the gut?
Between November 2018 and October 2019, carbapenem-resistant Enterobacterales carrying New Delhi Metallo-β-lactamase (NDM) caused one of the largest and persistent outbreaks occurred in Italy and ...intensified surveillance measures have been taken in all Italian hospitals.
In this study we analyzed NDM-5- producing Escherichia coli identified in 2 hospitals of the Lazio region in Italy.
Epidemiological and microbiological data demonstrated that in 2018-2019 the NDM-5-producing high-risk E. coli ST167 clone circulated in patients from both hospitals. In 2019, another NDM-5-producing E. coli clone, identified by MLST as ST617 was introduced in one of the 2 hospitals and caused an outbreak.
This study describes an application of genomics as a useful method to discern endemic and outbreak clones when applied to strains of the same species (E. coli) with the same resistance determinant (NDM-5) and the relevance of screening patients admitted in critical units for carbapenemase producers to prevent outbreaks.
Teicoplanin has a potential antiviral activity expressed against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and was suggested as a complementary option to treat coronavirus disease ...2019 (COVID‐19) patients. In this multicentric, retrospective, observational research the aim was to evaluate the impact of teicoplanin on the course of COVID‐19 in critically ill patients. Fifty‐five patients with severe COVID‐19, hospitalized in the intensive care units (ICUs) and treated with best available therapy were retrospectively analysed. Among them 34 patients were also treated with teicoplanin (Tei‐COVID group), while 21 without teicoplanin (control group). Crude in‐hospital Day‐30 mortality was lower in Tei‐COVID group (35.2%) than in control group (42.8%), however not reaching statistical significance (p = .654). No statistically significant differences in length of stay in the ICU were observed between Tei‐COVID group and control group (p = .248). On Day 14 from the ICU hospitalization, viral clearance was achieved in 64.7% patients of Tei‐COVID group and 57.1% of control group, without statistical difference. Serum C‐reactive protein level was significantly reduced in Tei‐COVID group compared to control group, but not other biochemical parameters. Finally, Gram‐positive were the causative pathogens for 25% of BSIs in Tei‐COVID group and for 70.6% in controls. No side effects related to teicoplanin use were observed. Despite several limitations require further research, in this study the use of teicoplanin is not associated with a significant improvement in outcomes analysed. The antiviral activity of teicoplanin against SARS‐CoV‐2, previously documented, is probably more effective at early clinical stages.
Highlights
‐Evidence from the scientific literature highlighted that a number of glycopeptide antibiotics have a potential antiviral activity expressed against Coronaviruses. Based on the aforementioned, teicoplanin was suggested as an alternative complementary option to treat also SARS‐CoV‐2 infected patients
‐Teicoplanin also remain a possible choice for treatment of Staphylococcus aureussuperinfection, a major complication of respiratory viral infections and in COVID related pneumonia.
‐This is the first multicentric, retrospective, observational analysis of a real‐life cohort of critically ill patients with COVID‐19 complementary treated with teicoplanin, used with a double purpose: as empiric antibiotic treatment and as antiviral agent (Tei‐COVID group). A control group untreated with teicoplanin was also enrolled
‐The results of this study showed that teicoplanin does not impact on the crude mortality in critically ill COVID‐19 patients: the primary outcome of the study failed due to lack of statistical significance despite mortality being lower in the Tei‐COVID group than in the control group (35.2% vs. 42.8%)
‐On Day 14 from the ICU hospitalization, viral clearance was achieved in 64.7% patients of Tei‐COVID group and 57.1% of control group, without statistical difference.
‐Serum C‐reactive protein level was significantly reduced in Tei‐COVID group compared to control group. No statistically significant differences were observed for white blood cells and lymphocytes counts, kidney and liver function, PO2/FiO2 and weaning from mechanical ventilation between the two groups at day 8.
‐ A possible explanation for these findings is that the antiviral activity of a drug is considered more effective at the onset of disease when viral replication and direct viral damage are still significant. As the disease progresses (the study enrolled critically ill patients), the damage is progressively sustained by pathogenic mechanisms not directly correlated with the presence of the virus, thus reducing the potential therapeutic role of antivirals at this stage.
PDF
