Background: Due to the growing resistance to routinely used antibiotics, the search for new antibiotics or their combinations with effective inhibitors against multidrug-resistant microorganisms is ongoing. In our study, we assessed the in vitro drug susceptibility of Klebsiella pneumoniae strains producing New Delhi metallo-β-lactamases (NDM) to antibiotics included in the Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommendations. Methods: A total of 60 strains of NDM-producing K. pneumoniae were obtained from different patients hospitalized at the 4th Military Hospital in Wroclaw between 2019 and 2022 and subjected to drug susceptibility to selected antibiotics, including the effects of drug combinations. Results: Among the tested antibiotics, the highest sensitivity (100%) was observed for cefiderocol, eravacycline (interpreted according to the European Committee on Antimicrobial Susceptibility Testing [EUCAST]), and tigecycline. Sensitivity to intravenous fosfomycin varied depending on the method used. Using the “strip stacking” method, determining cumulative sensitivity to ceftazidime/avibactam and aztreonam demonstrated 100% in vitro sensitivity to this combination among the tested strains. Conclusion: The in vitro susceptibility assessment demonstrated that, the best therapeutic option for treating infections caused by carbapenemase-producing strains seems to be a combination of ceftazidime/avibactam with aztreonam. Due to the safety of using both drugs, cost effectiveness, and the broadest indications for use among the tested antibiotics, this therapy should be the first-line treatment for carbapenemase-producing Enterobacterales infections. Nevertheless, a comprehensive evaluation of the efficacy of treating infections caused by NDM-producing K. pneumoniae strains should include not only in vitro susceptibility assessment but also an analysis of clinical cases.

Since the beginning of December 2022, an unusually high number of cases and deaths of Group A Streptococcus (GAS) infections has been reported in many European countries. GAS infection frequently causes mild diseases such as pharyngitis, tonsillitis, impetigo, cellulitis, and scarlet fever. However, in rare instances, GAS infection can lead to invasive, life-threatening conditions like necrotizing fasciitis and toxic shock syndrome, which are associated with high mortality. The aim of the study was to present the clinical course of invasive Streptococcus pyogenes infections and to highlight the increase in the incidence of severe infections of this etiology, similar to trends observed in other European countries. The study included 11 patients with severe, invasive infections caused by S. pyogenes accompanied by sepsis or septic shock, treated at the 4th Clinical Military Hospital in Wroclaw between December 2022 and May 2023. Among 11 patients, 6 had streptococcal skin and soft tissue infections, 3 had pneumonia caused by S. pyogenes, 1 had streptococcal otitis, and 1 had a knee joint infection. Nine developed septic shock, and three died from fulminant streptococcal toxic shock syndrome (STSS). Physicians should be aware of the increased prevalence of invasive GAS (iGAS) infections; timely diagnosis and effective treatment are crucial to reducing the risk of severe complications, including death.

Bloodstream infections (BSIs) are associated with high mortality and inappropriate or delayed antimicrobial therapy. The purpose of this study was to investigate the impact of the COVID-19 pandemic on the epidemiology of BSIs in hospitalized patients. The research aimed to compare the incidence of BSIs and blood culture results in patients hospitalized before and during the COVID-19 pandemic. Methods: Retrospective and prospective data were collected from blood cultures obtained from 4289 patients hospitalized between June 2018 and July 2022. Two groups of patients were distinguished: those with BSIs admitted during the pre-COVID-19 period and those admitted during the COVID-19 surge. Demographic and clinical data, blood cytology, and biochemistry results were analyzed, and the usefulness of PCT was assessed in patients with COVID-19. Results: The study showed a significant increase in the incidence of BSIs during the pandemic compared to the pre-COVID-19 period. Positive blood cultures were obtained in 20% of patients hospitalized during the pandemic (vs. 16% in the pre-COVID-19 period). The incidence of BSIs increased from 1.13 to 2.05 cases per 1000 patient days during COVID-19, and blood culture contamination was more frequently observed. The mortality rate was higher for patients hospitalized during the COVID-19 pandemic. An increased frequency of MDRO isolation was observed in the COVID-19 period. Conclusions: The incidence of BSIs increased and the mortality rate was higher in the COVID-19 period compared to the pre-COVID-19 period. The study showed limited usefulness of procalcitonin in patients with COVID-19, likely due to the administered immunosuppressive therapy.

A retrospective study at the 4th Military Clinical Hospital in Wroclaw, Poland, assessed PCR testing alongside blood cultures to guide antimicrobial therapy decisions in hospitalized patients, to determine how much time the results of the molecular tests preceded conventional methods. Among 118 patients, Staphylococcus aureus (37%) and Escherichia coli (21%) were the most common bloodstream infection agents. Blood cultures utilized the BacT/ALERT 3D system, and molecular diagnostics were conducted using the FilmArray platform with the BIOFIRE BCID2 panel. Methicillin susceptibility was observed in 66% of S. aureus strains, while 26% of Gram-negative bacilli exhibited an ESBL phenotype. Therapeutic decisions based on molecular test results were often incorrect for S. aureus infections, particularly MSSA (64.5%), but generally accurate for Gram-negative bacilli. The median times from positive blood culture to BCID2 and pathogen identification/susceptibility were 10 h and 52 h, respectively. Molecular diagnostics facilitated faster initiation of appropriate antibiotic therapy, highlighting the need to educate medical staff on proper interpretation. Consulting within an antimicrobial stewardship program (ASP) could enhance the benefits of implementing molecular methods in bloodstream infection diagnostics.

Fungi are one of the major causes of opportunistic infections in people living with HIV/AIDS. Pneumocystis jirovecii, Cryptococcus neoformans, Histoplasma capsulatum, and Candida spp. are especially more likely to affect HIV-infected individuals. Introduction and broad use of antiretroviral therapy have led to a significant decrease in invasive fungal infections in HIV-positive patients. Still, in untreated/abandoned HIV-infected individuals or patients with poor adherence to antiretroviral therapy, fungal infections may lead to severe clinical complications and death. In recent years, data have shown a growing number of immunocompromised patients due to malignancies, immunosuppressive therapies, and transplantations in the general population, and the number of susceptible individuals to fungal infections is increasing. Moreover, rising antifungal resistance is a serious threat to public health. This article provides an overview of common fungal infections in patients with HIV and discusses the changes in epidemiology and etiology, as well as current therapeutic challenges.

Recently, a rapid spread of carbapenemase-producing Enterobacterales (CPE) strains has been observed worldwide, including in Poland, which represents a severe epidemiological and therapeutic problem. CPE most often colonizes the gastrointestinal tract but can also cause urinary tract infections (UTIs), pneumonia, or blood stream infection. Antimicrobial resistance genes are included in mobile elements such as plasmids, transposons, and integrons. The importance of these elements lies in their role in the vertical transmission of genes from K. pneumoniae to its descendants, as well as the horizontal transmission of genes from a specific K. pneumoniae strain to another (Karampatakis et al., 2023). These microorganisms spread very quickly in the hospital environment, primarily through direct contact with another patient who is a carrier of CPE or through the hands of medical staff. Screening of patients from risk groups during admission to the hospital, adherence to hand hygiene procedures by medical staff, and the application of rational antibiotic therapy in healthcare units, constitute the primary tool in the fight against spreading of CPE infections. (Otter et al., 2020).Most CPE strains are completely resistance to commonly used antibiotics, that is why, treating infections caused by these microorganisms often requires new, unconventional antibiotics or combination antibiotic therapy based on two or even three drugs. Unfortunately, in the case of CPE strains, there are often only one or two therapeutic options left for treatment, and there are also situations in which the strain is entirely resistant to all known antibiotics. Therefore, both laboratories and clinicians are forced to look for combinations of "old" and "new" antibiotics, the combined action of which may provide a chance for therapeutic success (Karaiskos et al., 2019;Ontong et al., 2021). Recently registered new antibiotics such as plazomicin, eravacycline or cefiderocol, may be an effective remedy in the fight against infections caused by CPE strains (Castanheira et al., 2020;McCreary et al., 2021;Zou et al., 2023).In 2021, the European Society of Clinical Microbiology and Infection Diseases (ESCMID) published recommendations containing proposed treatment regimens for infections caused by third-generation cephalosporins-resistant microorganisms and Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii that are resistance to carbapenems (Paul et al., 2022).In the case of enterobacterial rod-producing metallo-β-lactamases, in patient with severe infections, it is recommended to use cefiderocol or combination of aztreonam with ceftazidim/avibactam. In particular, the synergistic effects of a variety of aztreonam combined with ceftazidime/avibactam deserves attention. Further, the sensitivity of CRE-MBL to old antibiotics, including polymyxins, tigecycline, or fosfomycin IV, has been reported. In each of these cases, the drug susceptibility of the individual strains should be determined. In 2021 and 2023, similar recommendations were made by the Infectious Diseases Society of America (IDSA) (Tamma et al., 2023).The MIC (Minimum Inhibitory Concentration) method is commonly employed in microbiological diagnostics to determine the lowest concentration of an antimicrobial agent that effectively inhibits the growth of a specific microorganism. There are also more specialized diagnostic tools to assess the interaction of two different antibiotics. This effect may be synergistic, additive, neutral, or antagonistic. Choosing this reciprocal relationship between the two drugs is a crucial therapeutic clue in treating infections caused by carbapenemase-producing Enterobacterales (Massoni-Cristante et al., 2003;Avery and Nicolau, 2018;Maraki et al., 2021;Terbtothakun et al., 2021).Among carbapenemases such as IMP (active against imipenem; imipenemase), VIM (Verona integron-encoded metallo-β-lactamase), KPC (Klebsiella pneumoniae carbapenemase), New Delhi metallo-β-lactamases (NDM), and OXA-48-like, NDM constitutes a critical medical issue. The effectiveness of almost all β-lactams, including carbapenems, is compromised by this enzyme, except for aztreonam and cefiderocol. Given that, there are very few antibiotics available as therapeutic options. The objective of this study was to assess the susceptibility of clinical isolates of NDM-producing Klebsiella pneumoniae, recognized as a significant threat to public health and a common factor in nosocomial infections, to new antibiotics, including drugs recommended by the US Food and Drug Administration (FDA) (U.S. Food and Drug Administration, 2023), IDSA, and ESCMID for treatment of nosocomial and complicated infections, presented in Table 1.The study aimed to evaluate the sensitivity of K. pneumoniae NDM isolates obtained from patients with UTI, VAP, and BSI infections in the 4 th Military Hospital of Wroclaw from 2019-2022 to new antibiotics included in the IDSA and ESCMID recommendations.The study was carried out in the Microbiology Laboratory of the Laboratory Diagnostics Department of the 4 th Military Clinical Hospital in Wroclaw, based on material obtained in the Clinical Department of Anesthesiology and Intensive Care and other departments. K. pneumoniae NDM strains were obtained from patients' cultures of clinical materials collected for routine microbiological tests, which were subjected to drug susceptibility to selected antibiotics, including the effects of drug combinations 2.1 Ethics The study protocol was approved by the Bioethics Committee of the Lower Silesian Medical Chamber, Poland (approval no. 2/BNR/2023). Confidentiality and privacy were considered with regard to personal, laboratory, and clinical data. The study was carried out in accordance with the guidelines of the Declaration of Helsinki and Good Clinical Practice. Written informed consent was obtained from all participants prior to the study.Microorganisms A total of 60...