Optimization of Therapy and the Risk of Probiotic Use during Antibiotherapy in Septic Critically Ill Patients: A Narrative Review.

Optimizing the entire therapeutic regimen in septic critically ill patients should be based not only on improving antibiotic use but also on optimizing the entire therapeutic regimen by considering possible drug-drug or drug-nutrient interactions. The aim of this narrative review is to provide a comprehensive overview on recent advances to optimize the therapeutic regimen in septic critically ill patients based on a pharmacokinetics and pharmacodynamic approach. Studies on recent advances on TDM-guided drug therapy optimization based on PK and/or PD results were included. Studies on patients <18 years old or with classical TDM-guided therapy were excluded. New approaches in TDM-guided therapy in septic critically ill patients based on PK and/or PD parameters are presented for cefiderocol, carbapenems, combinations beta-lactams/beta-lactamase inhibitors (piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam), plazomicin, oxazolidinones and polymyxins. Increased midazolam toxicity in combination with fluconazole, nephrotoxic synergism between furosemide and aminoglycosides, life-threatening hypoglycemia after fluoroquinolone and insulin, prolonged muscle weakness and/or paralysis after neuromuscular blocking agents and high-dose corticosteroids combinations are of interest in critically ill patients. In the real-world practice, the use of probiotics with antibiotics is common; even data about the risk and benefits of probiotics are currently spares and inconclusive. According to current legislation, probiotic use does not require safety monitoring, but there are reports of endocarditis, meningitis, peritonitis, or pneumonia associated with probiotics in critically ill patients. In addition, probiotics are associated with risk of the spread of antimicrobial resistance. The TDM-guided method ensures a true optimization of antibiotic therapy, and particular efforts should be applied globally. In addition, multidrug and drug-nutrient interactions in critically ill patients may increase the likelihood of adverse events and risk of death; therefore, the PK and PD particularities of the critically ill patient require a multidisciplinary approach in which knowledge of clinical pharmacology is essential.

Antibiotic Usage in the COVID-19 Intensive Care Unit of an Infectious Diseases Hospital from Nord-Eastern Romania.

Background and Objectives. The intensive care unit (ICU), especially in an infectious disease hospital, is both an area with a high consumption of antibiotics (atb) and a "reservoir" of multidrug-resistant bacteria. We proposed the analysis of antibiotic therapy practices in such a department that treated, in conditions of a pandemic wave, patients with COVID-19 and its complications. Materials and Methods. This was a retrospective transversal study of 184 COVID-19 patients treated in the ICU of a regional infectious disease hospital of Iasi, Romania, in a 3-month interval of 2020 and 2021. Results. All the included patients (Caucasians, 53% males, with a median age of 68 years, and a Charlton comorbidity index of 3) received at least one antibiotic during their stay in the ICU (43% also had antibiotics prior to hospital admission and 68% in the Infectious Diseases ward). Only 22.3% of the ICU patients had only one antibiotic. A total of 77.7% of them started with an association of two antibiotics, and 19.6% of them received more than three antibiotics. The most-used ones were linezolid (77.2%), imipenem (75.5%), and ceftriaxone (33.7%). The median atb duration was 9 days. No change in the number or type of atb prescription was seen in 2021 (compared to 2020). Only 9.8% of the patients had a microbiological confirmation of bacterial infection. A total of 38.3% of the tested patients had elevated procalcitonin levels at ICU admission. The overall fatality rate was 68.5%, with no significant differences between the two analyzed periods or the number of administered antibiotics. More than half (51.1%) of the patients developed oral candidiasis during their stay in the ICU, but only 5.4% had C. difficile colitis. Conclusion. Antibiotics were widely used in our ICU patients in the presence of a reduced microbiological confirmation of a bacterial co-infection, and were justified by other clinical or biological criteria.

Polymicrobial Bacterial Meningitis in a Patient with Chronic Suppurative Otitis Media: Case Report and Literature Review.

Polymicrobial meningitis is a rare entity in the adult population, especially in the antibiotic era. However, disorders such as chronic suppurative otitis media (CSOM) or even poor oral hygiene are considered risk factors for the development of such cerebral infection. We report a case of polymicrobial meningitis associated with oto-mastoiditis in a 64-year-old female patient known to have CSOM. The patient presented atypical symptoms for community-acquired meningitis, showing subacute evolution of headache, without fever or neck stiffness. The aerobe microorganisms Streptococcus anginosus and Corynebacterium spp., sensitive to beta-lactamines, and the anaerobe Prevotella spp., resistant to penicillin and metronidazole, were isolated from CSF specimens, while Proteus mirabilis and Enterococcus faecalis were identified from the ear drainage. The diversity of pathogens identified in our case led us to the hypothesis of two different sources of meningitis: otogenic and/or odontogenic. Favorable evolution was obtained after a multi-disciplinary approach, combining surgery and broad-spectrum antibiotics. In addition, we performed a literature review that highlights the low incidence of polymicrobial mixed aerobe-anaerobe meningitis.

The Clash of the Titans: COVID-19, Carbapenem-Resistant Enterobacterales, and First mcr-1-Mediated Colistin Resistance in Humans in Romania.

(1) Background: Antibiotic resistance and coronavirus disease-19 (COVID-19) represent a dual challenge in daily clinical practice, inducing a high burden on public health systems. Hence, we aimed to dynamically evaluate the impact of COVID-19 on patients with carbapenem-resistant Enterobacterales (CRE) urinary tract infections (UTIs), as well as the antibiotic resistance trends after the onset of the pandemic. (2) Methods: We conducted a prospective study including patients with CRE UTIs who were enrolled both pre- and during the pandemic from 2019 to 2022. We further performed a standardized and comparative clinical, paraclinical, and microbiological assessment between patients with and without COVID-19. (3) Results: A total of 87 patients with CRE UTIs were included in this study (46 pre-pandemic and 41 during the pandemic, of which 21 had associated Severe Acute Respiratory Syndrome Coronavirus-2 infection). Klebsiella pneumoniae was the main etiological agent of the UTIs, with the majority of strains (82.7%) being carbapenemase producers (mainly OXA-48 producers), while five of the 34 colistin-resistant isolates were harboring the mobile colistin resistance-1 (mcr-1) gene. COVID-19 patients presented a significantly worse outcome with higher rates of intensive care unit (ICU) admissions (66.7% for COVID patients vs. 18.2% for non-COVID patients, p < 0.001), while the fatality rates were also considerably higher among patients with concomitant viral infection (33.3% vs. 12.1%, p < 0.001). Besides COVID-19, additional risk factors associated with increased mortality were urinary catheterization, sepsis with K. pneumoniae, impaired liver and kidney function, and an inappropriate initial empiric antibiotic therapy. (4) Conclusions: COVID-19 showed a pronounced negative impact on patients with CRE UTIs, with significantly longer hospitalizations and higher ICU admissions and mortality rates.

Mortality Predictors in Severe COVID-19 Patients from an East European Tertiary Center: A Never-Ending Challenge for a No Happy Ending Pandemic.

(1) Background: There are limited clinical data in patients from the Eastern European regions hospitalized for a severe form of Coronavirus disease 2019 (COVID-19). This study aims to identify risk factors associated with intra-hospital mortality in patients with COVID-19 severe pneumonia admitted to a tertiary center in Iasi, Romania. (2) Methods: The study is of a unicentric retrospective observational type and includes 150 patients with severe COVID-19 pneumonia divided into two subgroups, survivors and non-survivors. Demographic and clinical parameters, as well as comorbidities, laboratory and imaging investigations upon admission, treatments, and evolution during hospitalization were recorded. First, we sought to identify the risk factors associated with intra-hospital mortality using logistic regression. Secondly, we assessed the correlations between D-Dimer and C-reactive protein and predictors of poor prognosis. (3) Results: The predictors of in-hospital mortality identified in the study are D-dimers >0.5 mg/L (p = 0.002), C-reactive protein >5 mg/L (p = 0.001), and heart rate above 100 beats per minute (p = 0.001). The biomarkers were also significantly correlated the need for mechanical ventilation, admission to intensive care unit, or multiple organ dysfunction syndrome. By area under the curve (AUC) analysis, we noticed that both D-Dimer (AUC 0.741) and C-reactive protein (AUC 0.707) exhibit adequate performance in predicting a poor prognosis in patients with severe viral infection. (4) Conclusions: COVID-19's outcome is significantly influenced by several laboratory and clinical factors. As mortality induced by severe COVID-19 pneumonia is considerable, the identification of risk factors associated with negative outcome coupled with an early therapeutic approach are of paramount importance, as they may significantly improve the outcome and survival rates.