Carbapenem-Resistant NDM and OXA-48-like Producing K. pneumoniae: From Menacing Superbug to a Mundane Bacteria; A Retrospective Study in a Romanian Tertiary Hospital.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (Cr-Kpn) is becoming a growing public health problem through the failure of adequate treatment. This study's objectives are to describe the sources of Cr-Kpn in our hospital over 22 months, associating factors with the outcome of Cr-Kpn-positive patients, especially those with NDM+OXA-48-like (New Delhi Metallo-ß-Lactamase and oxacillinase-48), and the effectiveness of the treatments used. METHODS: A retrospective observational cohort study including all hospitalized patients with Cr-Kpn isolates. We reported data as percentages and identified independent predictors for mortality over hospital time through multivariate analysis. RESULTS: The main type of carbapenemases identified were NDM+OXA-48-like (49.4%). The statistical analysis identified that diabetes and co-infections with the Gram-negative, non-urinary sites of infection were factors of unfavorable evolution. The Cox regression model identified factors associated with a poor outcome: ICU admission (HR of 2.38), previous medical wards transition (HR of 4.69), and carbapenemase type NDM (HR of 5.98). We did not find the superiority of an antibiotic regimen, especially in the case of NDM+OXA-48-like. CONCLUSIONS: The increase in the incidence of Cr-Kpn infections, especially with NDM+OXA-48-like pathogens, requires a paradigm shift in both the treatment of infected patients and the control of the spread of these pathogens, which calls for a change in public health policy regarding the use of antibiotics and the pursuit of a One Health approach.

Unveiling the potential role of micro/nano biomaterials in the treatment of Helicobacter pylori infection.

INTRODUCTION: Helicobacter pylori causes stubborn infections and leads to a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. Although antibiotic-based approaches have been widely used against H. pylori, some challenges such as antibiotic resistance are increasing in severity. Therefore, simpler but more effective strategies are needed. AREAS COVERED: In this review, basic information on functionalized and non-functionalized micro/nano biomaterials and routes of administration for H. pylori inhibition are provided in an easy-to-understand format. Afterward, in vitro and in vivo studies of some promising bio-platforms including metal-based biomaterials, biopolymers, small-molecule saccharides, and vaccines for H. pylori inhibition are discussed in a holistic manner. EXPERT OPINION: Functionalized or non-functionalized micro/nano biomaterials loaded with anti-H. pylori agents can show efficient bactericidal activity with no/slight negative influence on the host gastrointestinal microbiota. However, this claim needs to be substantiated with hard data such as assessment of the biopharmaceutical parameters of anti-H. pylori systems and the measurement of diversity/abundance of bacterial genera in the host gastric/gut microbiota before and after H. pylori eradication.

Infections in hospitalised patients affected by end-stage diseases: a narrative overview.

AIM: To analyse the presence and treatment of infections in hospitalised terminal patients by identifying potential risk factors. METHODS: We conducted a retrospective study using health data from 229 terminally ill patients (evaluated by our hospital palliative care team (HPCT) hospitalised from January to December 2018. RESULTS: A total of two types of infections were identified: blood flow infection (through blood cultures) and pneumonia (through radiological examinations), while the other cases of infection remained unknown. The most frequently identified microorganism was Staphylococcus spp. The prevalence of infections was higher in patients with non-oncological diseases (n=47, 36.7%; p value 0.009). The potential risk factors identified for infections were the presence of: Parkinson's disease (n=15, 11.7%; p value 0.005), dysphagia (n=49, 38.3%; p value 0.007), bedding (n=15, 11.7%; p value 0.048), pressure ulcers (n=31, 24. 2%); p value 0.018), oxygen therapy (n=60, 46.9%; p value 0.050), urinary catheters (n=95, 74.2%; p value 0.038) and polypathology (2.3 vs 1.7; p value 0.022). Parkinson's disease (OR=5.973; 95% CI=1.292-27.608), dysphagia (OR=2.090; 95% CI=1.080-4.046) and polypathology (OR=1.220; 95% CI=1.015-1.466) were confirmed by a corrected logistic regression analysis. CONCLUSIONS: Infections and, consequently, antibiotic therapies, have a high prevalence in hospitalised patients with terminal disease. Potential risk factors for infections in these patients could be polypathology, dysphagia and Parkinson's disease. Patients with these conditions could benefit from prevention programmes.

pH-Responsive Fluorescent Polymer-Drug System for Real-Time Detection and In Situ Eradication of Bacterial Biofilms.

Bacterial biofilms encased in extracellular polymeric substances to create protected microenvironments are typically challenging to disperse by common antibiotics and cannot be in situ visualized under current modalities. Herein, a pH-responsive branched polymer [poly(MBA-AEPZ)-AEPZ-NA] capable of overcoming antibiotic resistance and real-time visualizing biofilms for fluorescence imaging-guided infection control is reported. The positively charged polymer can effectively penetrate bacterial biofilms, neutralize the anionic character, and then disrupt the structural integrity, thus significantly promoting the transport of antibiotics into biofilms. The polymer shows a weak fluorescence emission intensity under physiological conditions (pH 7.4) but emits intense green-light emission within the localized biofilm microenvironment (pH 5.5) to real-time visualize bacterial biofilms. A therapeutic system made of the polymer and a model antibiotic can significantly reduce the dosages of the drug, thereby minimizing biofilm-induced drug resistance. Notably, a green fluorescent polymer responding to localized pH conditions is demonstrated in living zebrafish. This work confirmed that combinations of the pH-responsive branched polymer and antibiotics could be administered to overcome drug resistance and realize fluorescence imaging-guided treatment of bacterial biofilm infections.

Absinthe against multi-drug resistant bacterial pathogens? A recent update on the antibacterial effects of Artemisia compounds.

The widespread misuse of antibiotics leads to a rapid development of multi-drug resistant (MDR) bacterial pathogens all over the globe, resulting in serious difficulties when treating infectious diseases. Possible solutions are not limited to the development of novel synthetic antibiotics but extend to application of plant-derived products either alone or in combination with common antibiotics. The aim of this actual review was to survey the literature from the past 10 years regarding the antibacterial effects of distinct Artemisia species including Artemisia absinthiae constituting an integral component of the Absinthe drink. We further explored the synergistic antibacterial effects of the Artemisia plant products with established antibiotics. The survey portrays the Artemisia derived compounds as potent antibacterial agents that can even restore the efficacy of antibiotics against MDR bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and MDR Escherichia coli. This, in turn, is presumably triggered in part by the interaction of the Artemisia ingredients with the efflux pumps of MDR bacteria. In conclusion, biologically active molecules in Artemisia plants enhance the antibiotic susceptibility of resistant bacteria, which provide promising future therapeutic strategies to combat MDR bacterial pathogens.

Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSA.

AIMS: Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. METHODS: For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. RESULTS: Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. CONCLUSION: Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143-151.