Search Results (50)

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Introduction: The World Health Organization has declared carbapenem-resistant organisms a research and development priority. Although ceftazidime–avibactam was approved around a decade ago, there is still a lack of prospective data on the treatment of resistant pathogens with this agent. Methods: We conducted a prospective, observational, single-center, investigator-initiated study of patients treated with ceftazidime–avibactam for infections caused by carbapenem-resistant organisms. The primary outcome was clinical cure 14 days after the initiation of ceftazidime-avibactam treatment. Secondary outcomes, which were assessed on day 30, included microbiological failure, development of resistance, all-cause mortality, and length of stay in the intensive care unit. Results: A total of 50 patients were included in the study. At baseline, the median Charlson Comorbidity Index and Sequential Organ Failure Assessment Score were 5.5 and 7. Approximately three-quarters of the patients were treated in an intensive care unit and had undergone mechanical ventilation within the previous 7 days prior to the commencement of ceftazidime–avibactam treatment. Half of the patients were diagnosed with nosocomial pneumonia. Most infections were caused by Pseudomonas aeruginosa (48%) and Klebsiella pneumonia (28%). Clinical cure at day 14 was achieved in 59% of patients. Four deaths (9%) and two cases of microbiological failure (4%) were observed. The median length of stay in the intensive care unit was 14 days. There was no emergence of resistance to ceftazidime–avibactam. Discussion: Our study contributes to the growing body of evidence supporting the effectiveness of ceftazidime–avibactam in treating infections caused by carbapenem-resistant organisms. In this cohort of critically ill patients, our results in terms of both clinical success and survival are in the upper range compared to those from mainly retrospective and some prospective studies. Although the benefits of ceftazidime–avibactam have been demonstrated in this and other studies, it must be prescribed cautiously to ensure it remains effective. Full article

Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients with advanced liver dysfunction. The global rise in these conditions underscores the need for effective interventions. Natural products have attracted attention for their potential to support liver health, particularly through synergistic combinations of plant extracts. Epavin, a dietary supplement from Erbenobili S.r.l., formulated with plant extracts like Taraxacum officinale (L.), Silybum marianum (L.) Gaertn., and Cynara scolymus (L.), known for their liver-supporting properties, has been proposed as adjuvant for liver functions. The aim of this work was to evaluate of Epavin’s antioxidant, anti-inflammatory, and protective effects against heavy metal-induced toxicity. In addition, the antibacterial effect of Epavin against a panel of bacterial strains responsible for infections associated with liver injuries has been evaluated. Methods: The protection against oxidative stress induced by H₂O₂ was evaluated in HepG2 and BALB/3T3 cells using the dichlorofluorescein diacetate (DCFH-DA) assay. Its anti-inflammatory activity was investigated by measuring the reduction in nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages using the Griess assay. Additionally, the cytoprotecting of Epavin against heavy metal-induced toxicity and oxidative stress were evaluated in HepG2 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) and DCFH-DA assays. The antibacterial activity of Epavin was assessed by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against Gram-positive (Enterococcus faecalis ATCC 29212, and BS, Staphylococcus aureus 25923, 29213, 43300, and BS) and Gram-negative (Escherichia coli 25922, and BS, Klebsiella pneumoniae 13883, 70063, and BS) bacterial strains using the microdilution method in broth, following the Clinical and Laboratory Standards Institute’s (CLSI) guidelines. Results: Epavin effectively reduced oxidative stress in HepG2 and BALB/3T3 cells and decreased NO production in LPS-stimulated RAW 264.7 macrophages. Moreover, Epavin demonstrated a protective effect against heavy metal-induced toxicity and oxidative damage in HepG2 cells. Finally, it exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 1.5 to 6.0 mg/mL. Conclusions: The interesting results obtained suggest that Epavin may serve as a valuable natural adjuvant for liver health by enhancing detoxification processes, reducing inflammation, and exerting antibacterial effects that could be beneficial in the context of liver-associated infections. Full article

Adrenomedullin (AM) is a bioactive peptide that is strongly induced during severe inflammation, including pneumonia and sepsis, and serves as an organ-protective factor. The plasma concentration of AM is markedly increased in the novel coronavirus disease COVID-19 and is closely related to the severity of the disease and prognosis of patients. We performed two investigator-initiated trials to evaluate the efficacy and safety of AM in patients with moderate-to-severe COVID-19. This multicenter, double-blind, placebo-controlled phase-2a trial evaluated COVID-19 patients with severe (n = 33) and moderate (n = 31) pneumonia in Japan. Patients were randomly assigned to receive either 15 ng/kg/min AM or placebo. The primary endpoint was the duration of mechanical ventilation (MV) for severe pneumonia and oxygen support for moderate pneumonia. The main secondary endpoint was clinical status up to 30 days after the intervention. No differences in primary or secondary endpoints were observed between the AM and placebo groups in patients with severe or moderate pneumonia. In the severe pneumonia group, three patients in the placebo group died due to respiratory failure, and one patient in the AM group died due to respiratory failure. The respiratory function test at 30 days in the moderate pneumonia group tended to be better than that in the AM group and approached significance (p = 0.073). Although mild adverse events caused by the vasodilatory effects of AM were noted, the safety of AM for treating pneumonia was confirmed. In these trials, we did not observe a definitive efficacy of AM in moderate to severe pneumonia. Alternative strategies for the treatment of AM in pneumonia require further research. Full article

Background: Respiratory infections (RIs) are a common cause of care by Prehospital Emergency Medical Services (PEMS). Early Warning Scores (EWS) are tools used by PEMS to assess patients with acute pathology. However, there is little evidence of their application in RIs. The primary aim of this study was to assess the ability of five EWS to predict one-year mortality (M1Y) and two-year (M2Y) mortality in patients with suspected RI assisted by PEMS. The secondary objective was to perform a survival analysis. Methods: An observational and prospective study was conducted in adult patients with RIs transferred by EMS to their referral hospital. The variables necessary for the calculation of EWS [National Early Warning Score 2 (NEWS2), Quick Sequential Organ Failure Assessment (qSOFA) score, Quick COVID-19 Severity Index (qCSI), CURB-65 Score for Pneumonia Severity (CURB-65) and BAP-65 Score for Acute Exacerbation of COPD (BAP-65) score] were collected. The prognostic ability of the EWS was assessed by the area under the receiver operating characteristic curve (AUC). Patients were followed up and a survival study was performed. Results: A total of 819 patients met the inclusion criteria. M1Y was 55.9% and M2Y was 63.5%. BAP-65 showed the best predictive ability at both 1 and 2 years, with AUC of 0.716 and 0.711, respectively. 48.8% of deaths took place during the first month. Conclusions: BAP-65 was the score with the best ability to predict both M1Y and M2Y after the index event in patients with RIs. All other EWS analyzed showed poor performance except in patients with low comorbidity. Full article

Background: Influenza B usually causes mild illness in children. Severe and fatal cases can occur when complicated by secondary Staphylococcus aureus (S. aureus) pneumonia, including community-acquired methicillin-resistant Staphylococcus aureus (MRSA). We present a rare, rapidly progressive fatal case in an adolescent with no known medical history to highlight diagnostic and therapeutic pitfalls. Case Presentation: A 16-year-old boy with no known underlying conditions (unvaccinated for influenza) presented critically ill at “Sf. Ioan” Clinical Emergency Pediatric Hospital in Galați after one week of high fever and cough. He was in respiratory failure with septic shock, requiring immediate intubation and vasopressors. Chest X-ray (CXR) showed diffuse bilateral infiltrates (acute respiratory distress syndrome, ARDS). Initial laboratory tests revealed leukopenia, severe thrombocytopenia, disseminated intravascular coagulation (DIC), rhabdomyolysis, and acute kidney injury (AKI). Reverse transcription polymerase chain reaction (RT-PCR) confirmed influenza B, and blood cultures grew MRSA. Despite maximal intensive care, including mechanical ventilation, antibiotics (escalated for MRSA), antiviral therapy, and cytokine hemoadsorption therapy, the patient developed refractory multi-organ failure and died on hospital day 6. Autopsy revealed bilateral necrotizing pneumonia (NP) without radiographic cavitation, underscoring the diagnostic challenge. Discussion: The initial chest radiography showed diffuse bilateral pulmonary infiltrates, predominantly in the lower zones, with an ill-defined, patchy, and confluent appearance. Such appearance, in our case, was more suggestive of rapid progressive NP caused by MRSA rather than the typical pneumococcal one. This is one of the few reported cases of influenza B–MRSA coinfection with fulminant rhabdomyolysis and autopsy-confirmed necrosis. Our fulminant case illustrates the synergistic virulence of influenza and MRSA. Toxin-producing MRSA strains can cause NP and a “cytokine storm,” causing capillary leak, ARDS, shock, and DIC. Once multi-organ failure ensues, the prognosis is grim despite aggressive care. The absence of early radiographic necrosis and delayed anti-MRSA therapy (initiated after culture results) likely contributed to the poor outcome. Conclusions: Influenza B–MRSA co-infection, though rare, demands urgent empiric anti-MRSA therapy in severe influenza cases with leukopenia or shock, even without radiographic necrosis. This fatal outcome underscores the dual imperative of influenza vaccination and early, aggressive dual-pathogen targeting in high-risk presentations. Full article

Background/Objectives: The clinical forms of coronavirus disease 2019 (COVID-19) vary widely in severity, ranging from asymptomatic or moderate cases to severe pneumonia that can lead to acute respiratory failure, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Our main objective was to determine the prevalence of bacterial and fungal secondary infections in an intensive care unit (ICU). Secondary objectives included analyzing the impact of these infections on mortality and medical resource utilization, as well as assessing antimicrobial resistance in this context. Methods: We conducted a retrospective cohort study that included critically ill severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients treated in an ICU and analyzed the prevalence of co-infections and superinfections. Results: A multivariate analysis of mortality found that the presence of superinfections increased the odds of death by more than 15-fold, while the Sequential Organ Failure Assessment (SOFA) score and C-reactive protein (adjusted for confounders) increased the odds of mortality by 51% and 13%, respectively. The antibiotic resistance profile of microorganisms indicated a high prevalence of resistant strains. Carbapenems, glycopeptides, and oxazolidinones were the most frequently used classes of antibiotics. Among patients, 27.9% received a single antibiotic, 47.5% received two from different classes, and 24.4% were treated with three or more. Conclusions: The incidence and spectrum of bacterial and fungal superinfections are higher in critically ill ICU patients, leading to worse outcomes in COVID-19 cases. Multidrug-resistant pathogens present significant challenges for ICU and public health settings. Early screening, accurate diagnosis, and minimal use of invasive devices are essential to reduce risks and improve patient outcomes. Full article

Background/Objectives: Data on multidrug-resistant organism (MDRO) infections in children are scarce, especially in resource-limited regions. This study aimed to estimate the prevalence of MDRO infections in pediatric intensive care units (PICUs) and characterize their epidemiologic and clinical features. Methods: A national, multicenter, point-prevalence study was conducted in 50 PICUs in Argentina over 24 h between 24 and 28 November 2023. The primary study outcome was the prevalence of ICU infections caused by MDROs. Secondary outcomes included the prevalence of carbapenemase-producing Enterobacterales (CPE) colonization, ICU mortality, and ICU length of stay (LOS_ICU). Results: 304 patients were included. The overall prevalence of infection was 45.1% (137/304); of these, 50.3% (69/137) were hospital-acquired. Among the 137 patients with reported infections, 49.6% (n = 68) were classified as definite (microbiologically confirmed) and 50.4% (n = 69) as probable (no confirmatory microbiology). Among definite infections, 20.6% (n = 14) were due to MDROs. The overall prevalence of MDRO infections was 4.6% (14/304). Extended-spectrum β-lactamase (ESBL)-producing organisms were the most commonly identified microorganisms (42.9%), followed by CPE (28.6%). Ventilator-associated pneumonia (VAP) was the most frequent location of MDRO infections. The prevalence of CPE colonization was 13.2%. Mortality was low (5.3%) and similar in patients with MDRO and non-MDRO infections. LOS_ICU was longer in patients with MDRO infections compared to patients with non-MDRO infections (81 [22–150] vs. 25 [12–27] days, respectively, p = 0.0007). Conclusions: Among 304 PICU patients, the prevalence of MDRO infections and colonization was relatively low. MDRO infections were not associated with increased mortality but were associated with longer ICU stays, compared to patients with non-MDRO infections. Full article

Background: Approximately two to three children die from pneumonia every hour, and pneumonia is the leading cause of hospitalization for children under five in Bangladesh. Bangladesh has adopted the Pocket Book guidelines by the World Health Organization (WHO) for hospital management of childhood pneumonia. These guidelines recommend the proper use of injectable antibiotic administration. Objectives: We assessed and compared the prescription drugs for treating childhood pneumonia following WHO guidelines in a secondary and tertiary hospital in Bangladesh. Methods: We conducted a cross-sectional comparative study among children under five years who were admitted to a tertiary hospital, Dhaka Medical College Hospital (DMCH), and a secondary-level hospital, Kushtia District Hospital (KDH), with pneumonia between May 2021 and May 2022. A structured questionnaire was administered to the eligible participants. Additionally, we reviewed the hospital records related to the patient’s treatment. SPSS (Version 28) was used to conduct statistical analysis. Results: 316 children were enrolled during the study period, of whom 66.4% were collected from DMCH. There were 65.8% and 24.6% of patients who were classified with severe pneumonia and very severe pneumonia, respectively. In DMCH, the severity of pneumonia percentage was 57.6%, while in KDH, the percentage was 82%. A significant difference was found between the two facilities in diagnosing complicated pneumonia, prescribing the appropriate antibiotics, and ensuring oxygen availability. Amoxicillin was prescribed to 83.5% of the participants, and ceftriaxone was used at a high rate (64.5–70.9%). Combining injections of ceftriaxone with oral amoxicillin or other combinations of antibiotics, both facilities used high frequencies of non-antibiotic corticosteroids. Conclusions: Antibiotics were overprescribed, and injections were prescribed at higher levels than WHO recommended. This could pose a threat to antibiotic resistance. There is a need to enforce standard prescribing policies and treatment guidelines to reduce morbidity and mortality among hospitalized children with pneumonia. Full article

Backgroud: This prospective randomized trial evaluated the clinical efficacy of inhaled colistin administered through two distinct nebulizer types, a vibrating mesh nebulizer (VMN) and a jet nebulizer (JN), in the treatment of ventilator-associated pneumonia caused by multidrug-resistant bacteria. In addition, an in vitro model was used to determine the optimal delivery of colistin. Method: Thirty-two patients prescribed intravenous (IV) colistin inhalation were randomized to receive either a VMN (n = 17) or a JN (n = 15), then compared to the control group (IV alone) over a 7-to 10-day period. The primary endpoint was the clinical pulmonary infection score (CPIS), and the secondary endpoints were the Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACE) score, and duration of ventilator use. Results: Results from in vitro testing demonstrated that VMN delivered a significantly higher colistin dose than JN (35.68 ± 3.55% vs. 23.56 ± 3.31%; p < 0.001) when positioned at the humidifier inlet. Compared to the IV alone group, the IV with inhalation group yielded significant improvements in CPIS, SOFA score, and APACHE score on day 7; nevertheless, clinical outcomes between the two nebulizers were statistically indistinguishable. Conclusions: In conclusion, although VMN delivers a higher dose in vitro, both nebulizers yielded comparable clinical outcomes. This study was registered at US Clinical Trial Registration (NCT04633317). Full article

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO₂) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO₂ levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO₂ at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO₂ of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation. Full article

Our aim was to determine the secondary antibody deficiency (SAD) profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, and clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin’s lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%, chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG < 400 mg/dL in 60.0%, IgA < 40 mg/dL in 55.0%, and CD19 < 20 cells/mm³ in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 3.0% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (p = 0.0001). Most patients progressed to hypo-γ-globulinemia and SAD after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases; therefore, monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement. Full article

(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over time of both Sequential Organ Failure Assessment (SOFA) score and inflammatory biomarkers in critically ill patients receiving continuous infusion (CI) monotherapy with piperacillin-tazobactam or meropenem for treating documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP). (2) Methods: We performed a retrospective observational study comparing critically ill patients receiving targeted treatment with CI meropenem monotherapy for documented Gram-negative BSIs or VAP with a historical cohort of critical patients receiving CI piperacillin-tazobactam monotherapy. Patients included in the two groups were admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 and fulfilled the same inclusion criteria. The delta values of the SOFA score between the baseline of meropenem or piperacillin-tazobactam treatment and those at 48-h (delta 48-h SOFA score) or at 7-days (delta 7-days SOFA) were selected as primary outcomes. Delta 48-h and 7-days C-reactive protein (CRP) and procalcitonin (PCT), microbiological eradication, resistance occurrence, clinical cure, multi-drug resistant colonization at 90-day, ICU, and 30-day mortality rate were selected as secondary outcomes. Univariate analysis comparing primary and secondary outcomes between critically ill patients receiving CI monotherapy with piperacillin-tazobactam vs. meropenem was carried out. (3) Results: Overall, 32 critically ill patients receiving CI meropenem monotherapy were compared with a historical cohort of 43 cases receiving CI piperacillin-tazobactam monotherapy. No significant differences in terms of demographics and clinical features emerged at baseline between the two groups. Optimal PK/PD target was attained in 83.7% and 100.0% of patients receiving piperacillin-tazobactam and meropenem, respectively. No significant differences were observed between groups in terms of median values of delta 48-h SOFA (0 points vs. 1 point; p = 0.89) and median delta 7-days SOFA (2 points vs. 1 point; p = 0.43). Similarly, no significant differences were found between patients receiving piperacillin-tazobactam vs. meropenem for any of the secondary outcomes. (4) Conclusion: Our findings may support the contention that in critically ill patients with documented Gram-negative BSIs and/or VAP, the decreases in the SOFA score and in the inflammatory biomarkers serum levels achievable with CI piperacillin-tazobactam monotherapy at 48-h and at 7-days may be of similar extent and as effective as to those achievable with CI meropenem monotherapy provided that optimization on real-time by means of a TDM-based expert clinical pharmacological advice program is granted. Full article

In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane–tazobactam, and meropenem–vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including bla_NMD-5 and bla_OXA derivative types, as well as a mutated outer membrane porin protein (OmpK37). Full article

The opportunistic pathogen Klebsiella pneumoniae (K. pneumoniae) can colonize mucosal surfaces and spread from mucosae to other tissues, causing fatal infections. Medical equipment and the healthcare setting can become colonized by Klebsiella species, which are widely distributed in nature and can be found in water, soil, and animals. Moreover, a substantial number of community-acquired illnesses are also caused by this organism worldwide. These infections are characterized by a high rate of morbidity and mortality as well as the capacity to spread metastatically. Hypervirulent Klebsiella strains are thought to be connected to these infections. Four components are critical to this bacterium’s pathogenicity—the capsule, lipopolysaccharide, fimbriae, and siderophores. Siderophores are secondary metabolites that allow iron to sequester from the surrounding medium and transport it to the intracellular compartment of the bacteria. A number of variables may lead to K. pneumoniae colonization in a specific area. Risk factors for infection include local healthcare practices, antibiotic use and misuse, infection control procedures, nutrition, gender, and age. Full article