Nosocomial Pneumonia Research Articles

Minimum inhibitory concentrations of antibacterial drugs for Staphylococcus epidermidis strains isolated from the contents of the tracheobronchial tree of newborn children

Introduction. Over the past decades, outstanding progress has been made in caring for extremely premature infants and newborns with severe pathologies. Management of this vulnerable category of patients is associated with the continued risk of developing infectious pathology. In the structure of nosological forms, neonatal sepsis caused by coagulase-negative staphylococci occupies one of the leading positions. There is an increase in the number of antibiotic-resistant strains, including among Staphylococcus epidermidis, a typical representative of the normal microbiocenosis of human skin, so colonization of a premature newborn child who is at the stationary stage of nursing with it is a typical process.Objective. To study changes in the minimum inhibitory concentration of antibacterial drugs for Staphylococcus epidermidis strains isolated from the contents of the tracheobronchial tree of newborn children at the nursing stage in a hospital setting.Material and methods. To assess the statistical significance of the results obtained, the Chisquare test with Yates correction and the Mann-Whitney U test were used. Research results. All strains tested were resistant to cefoxitin. This, in turn, determines resistance to protected penicillins, amoxicillin clavulanate, ampicillin, sulbactam, and cephalosporins of I-IV generations. 44.4% and 87.5% of Staphylococcus epidermidis strains resistant to gentamicin were registered in 2022 and 87.5% in 2024.When comparing the MIC to gentamicin of Staphylococcus epidermidis isolated from TBD, a significant increase in indicators was established in 2024 compared to 2022 (Mann-Whitney U test is 7.5; p<0.05). The proportion of clindamycin-resistant Staphylococcus epidermidis strains is 44.4% in 2022 and 12.5% in 2024 (p = 0.179). > < 0.05). The proportion of clindamycin-resistant Staphylococcus epidermidis strains is 44.4% in 2022 and 12.5% in 2024 (p = 0.179).Conclusion. Thus, the analysis of antibiotic resistance of staphylococci isolated during bacteriological examination of the contents of the tracheobronchial tree demonstrates an increase in the MIC of Staphylococcus epidermidis to gentamicin.The high therapeutic potential of vancomycin, a deep reserve antibiotic for the treatment of congenital and hospital-acquired pneumonia in premature newborns, remains high.

Ceftobiprole activity against multidrug-resistant Staphylococcus aureus clinical isolates collected in the United States from 2016 through 2022.

Ceftobiprole was recently approved by the United States (US) Food and Drug Administration (FDA) for the treatment of adult patients with Staphylococcus aureus bacteremia, including right-side endocarditis, acute bacterial skin and skin structure infections, and community-acquired bacterial pneumonia in adults and pediatrics. Ceftobiprole is an advanced-generation cephalosporin approved in many countries for the treatment of adults with community-acquired pneumonia and hospital-acquired pneumonia, excluding ventilator-associated pneumonia. We evaluated the activities of ceftobiprole and comparators against methicillin-resistant S. aureus (MRSA) and multidrug-resistant (MDR) S. aureus clinical isolates. A total of 19,764 S. aureus isolates were collected from patients with various infection types at 37 US medical centers from 2016 to 2022. Susceptibility testing was performed by broth microdilution according to Clinical and Laboratory Standard Institutes (CLSI) standards. Isolates were categorized as MDR if they were nonsusceptible by CLSI criteria to ≥3 antimicrobials. Ceftobiprole was highly active against MRSA (n = 8,184; MIC50/90, 1/2 mg/L; 99.3% susceptible [S]) and MDR (n = 2,789; MIC50/90, 1/2 mg/L; 98.1%S) isolates and retained activity against 87.3% of ceftaroline-nonsusceptible isolates (n = 433; MIC50/90, 2/4 mg/L). Ceftobiprole demonstrated greater susceptibility rates than ceftaroline against all resistant subsets. Ceftobiprole was highly active against isolates nonsusceptible to clindamycin (98.0%S), daptomycin (100.0%S), doxycycline (98.2%S), erythromycin (99.5%S), gentamicin (98.1%S), levofloxacin (99.1%S), tetracycline (99.1%S), tigecycline (100.0%S), and trimethoprim-sulfamethoxazole (99.4%S) and isolates with decreased susceptibility to vancomycin (98.3%S).

Clinical characteristics and prognostic analysis of concurrent Pneumocystis jirovecii pneumonia in patients with idiopathic inflammatory myopathy

Objective: To describe the clinical characteristics and to explore the prognostic factors of concurrent pneumocystis jirovecii pneumonia (PJP) in patients with idiopathic inflammatory myopathy (IIM). Methods: We retrospectively enrolled consecutive IIM patients diagnosed with PJP at our center between January 2014 and December 2022. Fifty-eight IIM-PJP patients were enrolled in our study, with the age of 26-79 (56.3±12.1) years. There were 19 males (32.9%) and 39 females (67.1%). The participants were classified into survival group (21 patients) and non-survival group (37 patients) according to the clinical outcome. Cox regression models were used to analyze the prognostic factors. Results: Compared with the survival group, there were more patients with anti- melanoma differentiation-associated gene (MDA5) positive, respiratory failure, hospital-acquired pneumonia, second-line PJP treatment, and caspofungin treatment in non-survival group (P<0.05). Meanwhile, the time from onset of IIM, corticosteroid therapy, and immunosuppressant medication to diagnosis of PJP was significantly shorter in non-survival patients than survival patients (P<0.05). Additionally, non-survival patients had higher neutrophil percentage and creatine kinase (P<0.05), and lower lymphocyte count and percentage, platelets, minimal albumin, NK cell count, T cell count, and CD8+T cell count (P<0.05). Multivariate analysis showed that anti-MDA5 positive (HR=3.54, P<0.05, 95%CI: 1.27-9.89), oral candidiasis infection (HR=2.62, P<0.05, 95%CI: 1.07-6.43) and thrombocytopenia (HR=5.00, P<0.01, 95%CI: 1.88-13.32) were independent risk factors for IIM-PJP patients. Conclusions: Middle-aged females were the main IIM-PJP in our group, and the mortality rate was 63.8%. Anti-MDA5 antibody positive, oral candidiasis infection, and thrombocytopenia were independent survival risk factors for them.

Echinacoside attenuates Klebsiella pneumoniae-induced pneumonia via inhibition of the TLR4/NF-κB signaling.

The Gram-negative bacterium Klebsiella pneumoniae (K. pneumoniae) is one major causative agent of community- and hospital-acquired pneumonia. Echinacoside (ECH) is a phenylethanoid glycoside isolated from Cistanche deserticola that possesses anti-inflammatory activity. Our research aimed to confirm whether ECH alleviates K. pneumoniae-induced pneumonia and explore the underlying regulatory mechanisms. BEAS-2B cells and BALB/c mice were infected by K. pneumoniae to establish the cellular and animal models, respectively, followed by ECH treatment. Inflammatory cytokine levels were detected by RT-qPCR and ELISA. The lung wet/dry (W/D) weight ratio and the myeloperoxidase (MPO) activity in lung tissues were examined. The pulmonary histopathologic changes were observed through hematoxylin and eosin (H&E) staining. The levels of TLR4/NF-κB pathway-associated molecules were estimated through western blotting, immunohistochemical, and immunohistochemical staining. K. pneumoniae infection caused lung histopathologic damage, enhanced MPO activity, elevated lung W/D weight ratio, and upregulated inflammatory cytokine levels in mice and promoted inflammatory cytokine expression in BEAS-2B cells, which were reversed by ECH treatment. K. pneumoniae infection-induced upregulation in TLR4, phosphorylated (p)-p65, and p-IκBα levels, and downregulation in IκBα levels in BEAS-2B cells and pneumonia mice were overturned by ECH treatment. ECH ameliorates K. pneumoniae-induced pneumonia through suppressing the TLR4/NF-κB pathway.

Bathing with 2% chlorhexidine gluconate versus routine care for preventing surgical site infections after pancreatic surgery: a single centre randomised controlled trial.

To investigate whether bathing with 2% chlorhexidine gluconate (CHG) reduces the incidence of surgical site infection (SSI) in patients undergoing routine pancreatic surgery. A randomised controlled trial was conducted at a large-volume pancreatic centre between 1 January 2021 and 31 December 2022. Patients undergoing clean-contaminated pancreatic surgery were enrolled and randomised into an intervention arm (bathing with a 2% CHG wipe) and a control arm (routine care, soap and water). The primary outcome was the incidence of SSI after pancreatic surgery within 30days. Overall, 614 patients (311, intervention arm; 303, control arm) were included in intention-to-treat (ITT) analysis. 8.8% (54/614) patients developed SSI. The incidence of SSI in intervention arm was 6.8% (21/311) and 10.9% (33/303) in control arm, and the difference did not reach the level of statistical significance (p=0.070). The time to SSI was significantly extended when patients in the intervention arm (log-rank test, p= 0.047). The intervention did not significantly reduce the incidence of healthcare-associated infection, hospital-acquired pneumonia, and bloodstream infection. No adverse events were observed. However, in the Per-Protocol (PP) analysis among 519 patients, the intervention arm showed a significantly lower incidence of overall SSI than that of those in the control arm (21/272, 7.7% vs. 33/242, 13.4%, p=0.036). Bathing with 2% chlorhexidine gluconate could potentially reduce the incidence of SSI for the patients scheduled to undergo pancreatic surgery which further well-designed clinical trials are warranted.

MINIMAL CHANGE DISEASE IN PEOPLE LIVING WITH HIV: A CASE REPORT AND REVIEW OF THE LITERATURE.

Various glomerular diseases are associated with human immunodeficiency virus (HIV) infection. However, the incidence of minimal change nephrotic syndrome has scarcely been reported. We describe a patient with a stage 4 HIV infection complaining of swelling in his face, hands, feet, genitals and an enlarged abdomen. Urinalysis revealed +3 proteins with normal urine sediment, and 2.1 g protein was found in the 24-hour analysis. Renal ultrasound showed bilateral glomerulopathies with hyperechoic and cortical thickening, a normal kidney size, and ascites. Kidney biopsy revealed acute tubular injury without HIV-associated nephropathy (HIVAN) features. The patient was treated with salt restriction, diuretics, captopril, methylprednisolone, and combined ART for 2 weeks and showed clinical improvement. Two weeks after the remission, the patient came to the outpatient department with a history of a 3-day cough with rust-colored sputum, fever, malaise, and shortness of breath. The lung auscultation revealed bilateral rhonchi and the chest x-ray result suggesting pneumonia. The patient was diagnosed with sepsis associated with healthcare-associated pneumonia but was not willing to be hospitalized and passed away at home. This study is limited to single-case nature and the possibility of sampling error. However, this case encourages further study in the field of HIV-associated renal diseases in providing clear recommendation in the management in special population.

Stress hyperglycaemia ratio is an independent predictor of in-hospital heart failure among patients with anterior ST-segment elevation myocardial infarction

BackgroundStress hyperglycaemia ratio (SHR) has been reported to be independently and significantly associated with various adverse cardiovascular events as well as mortality. Moreover, in-hospital heart failure following acute myocardial infarction has been demonstrated to account for majority of all heart failure (HF) cases with anterior myocardial infarction showing higher rates of HF. However, the association between SHR and in-hospital HF following an anterior ST-elevation myocardial infarction (STEMI) has not been reported earlier. Therefore, the present study aimed at identifying the relationship between SHR and in-hospital HF post STEMI.MethodsIn this retrospective study electronic health records of 512 patients who presented with anterior STEMI from 01 January 2022 to 31 January 2024 were analysed. Based on the development of in-hospital HF, the enrolled patients were stratified into two groups: Group I, comprising of 290 patients who developed in-hospital HF and Group II comprising of 222 patients who did not develop in-hospital HF. ROC and Multivariable logistic regression analyses were performed to assess the relationship between SHR and in-hospital HF.ResultsThe results revealed that SHR is a significant independent predictor of in-hospital HF (OR: 3.53; 95%CI: 2.02–6.15; p < 0.001). Apart from SHR, the results also identified age, nosocomial pneumonia, ventricular fibrillation, LVEF, and NT-pro-BNP levels as other independent predictors. ROC analysis showed that SHR independently had a moderate discriminative power with AUC: 0.683, 95% CI 0.605–0.762; p = 0.04, which was almost comparable to the combined predictive value of other independent risk factors (AUC: 0.726, 95% CI 0.677–0.784). Noticeably, combining SHR and other identified independent predictors demonstrated a significant predictive power (AUC: 0.813, 95% CI 0.757–0.881; p = 0.01).ConclusionSHR is an independent predictor for in-hospital HF in anterior wall STEMI patients.

Identifying predictors of nosocomial pneumonia in trauma patients admitted to a level-1 trauma center.

Nosocomial pneumonia is common in trauma patients and associated with an adverse prognosis. We recently externally validated and recalibrated an existing formula to predict nosocomial pneumonia risk. Identifying more potential predictors could aid in a more accurate prediction of nosocomial pneumonia risk in level-1 trauma patients. This study aims to identify predictors of nosocomial pneumonia in level-1 trauma patients available in the emergency department or shortly after, and examine their added predictive value to an existing prediction model by Croce. This retrospective cohort study included all consecutive trauma patients (≥ 16 years) admitted for > 24 h to our level-1 trauma center in 2017. Excluded were patients with active infection upon admission, transfer from another hospital, or in-hospital mortality < 48 h. Multiple imputations were used for missing values. Multivariable logistic regression analysis and Ridge penalization were performed to assess the association of predictors with nosocomial pneumonia and evaluate predictor stability. The predictive performance in addition to the existing prediction model was evaluated as well. The study included 809 patients [median age 51 (IQR 32-68) years, 66.9% male, median ISS 10 (5-17), median GCS score 15 (14-15)]. Pneumonia incidence was 10.6% (n = 86). Age (OR 1.03 per year), ISS (OR 1.10 per point), GCS score (OR 0.91 per point), pulmonary contusion (OR 2.77), male sex (OR 1.36), hypertension (OR 1.86), diabetes (OR 1.20), number of rib fractures (OR 1.05 per fractured rib), and thoracic spine fracture (OR 1.51) were found to be predictors of nosocomial pneumonia. All variables showed added predictive value in addition to the existing model. Patient history, injury severity, thoracic trauma, and traumatic brain injury are essential components of nosocomial pneumonia prediction and add to the predictive value of an existing model. Our results further build a basis for more accurate prediction. Level III, prognostic/epidemiological.

Alternative management of persistent Hyperinsulinemic hypoglycemia in a neonate: A case report on octreotide and nifedipine therapy

This case report highlights the successful management of Persistent Hyperinsulinemic Hypoglycemia in Infancy (PHHI) using alternative therapies, demonstrating their efficacy and practical implications in resource-limited settings. A 48-hour-old neonate presented with severe hypoglycemia unresponsive to high-dose glucose infusion. Laboratory investigations confirmed PHHI with elevated insulin and C-peptide levels. Due to the unavailability of diazoxide, treatment involved subcutaneous octreotide and oral nifedipine. The clinical course was managed and monitored according to international guidelines for hyperinsulinemic hypoglycemia. The combination therapy successfully stabilized blood glucose levels, enabling cessation of intravenous glucose infusion by day 10. The patient also recovered fully from hospital-acquired pneumonia with antibiotic treatment. These outcomes underscore the potential efficacy of nifedipine as a viable second-line therapy for PHHI in contexts where standard treatments are inaccessible. This case underscores the importance of flexible, evidence-based therapeutic approaches tailored to individual patient needs, especially in resource-constrained environments. The findings highlight nifedipine’s clinical utility in PHHI management and emphasize the need for further research, including large-scale studies, to establish standardized treatment protocols and expand access to effective therapies globally.

Does the treatment modality affect nosocomial pneumonia and other in-hospital outcomes in patients with combined injuries to the ribs and clavicle? A propensity score weighted analysis of a retrospective cohort.

What is the effect of surgical or conservative treatment on the in-hospital outcomes of patients with combined fractures of the clavicle and ribs? Retrospective cohort study. Two level-1 trauma centers and academic teaching hospitals in Boston, Massachusetts. All adult patients with a clavicle fracture and ≥3 rib fractures admitted from 2016 to 2021. None. Nosocomial pneumonia, hospital length-of-stay (HLOS), ICU length-of-stay (ILOS), days on mechanical ventilation (DMV). 252 patients were included (212 conservative, 40 surgical; median age 62 years, 67% male). The median ISS and GCS scores were 17 and 15, respectively. Thirty-seven patients developed nosocomial pneumonia. For clavicle fixation (n = 26), the OR for pneumonia was 0.3 (95% CI 0.0-2.2), ILOS had a ß-coefficient of -2.6 (95% CI -5.9-0.8), and DMV a ß-coefficient of -3.6 (95% CI -12.0-4.8). For rib plating (n = 10), the OR for pneumonia was 1.4 (95% CI 0.2-8.6), HLOS had a ß-coefficient of 4.9 (95% CI -1.6-11.5), and ILOS a ß-coefficient of 4.1 (95% CI -0.4-8.6). For both surgeries (n = 4), the CIs were wide. Clavicle fixation in patients with combined injuries of the clavicle and ribs did not improve nor worsen in-hospital outcomes; the orthopedic surgeon should make a patient-tailored treatment decision. Rib plating did not improve in-hospital outcomes in non-flail patients with a concomitant clavicle fracture. Guidelines on non-flail rib plating could profit from these findings in combination with previous and additional research. Level III, Therapeutic Study.

Emergence of Candida famata Fungemia in an Immunocompromised Patient: A Case Report Highlighting Clinical Presentation, Diagnosis, and Therapeutic Strategy

Candida famata, once regarded as benign, is now being recognized as an opportunistic pathogen. This case presents an 88-year-old male with multiple comorbidities who developed C. famata bloodstream infection during treatment for healthcare-associated pneumonia complicated by prolonged catheter use and hospital stay. Antifungal therapy with voriconazole led to clinical improvement and eventual discharge of the patient in stable condition. The rarity of C. famata infection presents diagnostic and therapeutic challenges. This case highlights the importance of timely antifungal therapy and a multidisciplinary approach in managing invasive candidiasis, particularly in immunocompromised patients. Further research is needed to optimize treatment.

Prevalence of multidrug-resistant gram-negative bacilli (MDR-GNB) in hospital-acquired and ventilator-associated pneumonia: A comparative study from a tertiary care center, Gujarat

Antibiotic resistance poses a formidable challenge to global healthcare, with Gram-negative bacteria emerging as a primary concern. Multidrug-resistant Gram-negative bacilli (MDR-GNB) have become a significant cause of nosocomial infections, particularly pneumonia, complicate therapy, and have a detrimental impact on patients’ outcomes. This study aims to investigate the etiology, risk factors, and antibiotic resistance patterns associated with Gram-negative bacilli (GNB) isolated from nosocomial pneumonia cases.This prospective cross-sectional study was conducted at the Microbiology laboratory of a tertiary care Hospital in Gujarat. Patients hospitalized for &amp;#62;48 hours with new lung infiltrates and at least two of the following clinical features: fever, leukocytosis/leukopenia, purulent secretions, or decreased oxygenation were included. The study was initiated after the ethical approval. Patient demographic and clinical details were noted in the preformed questionnaire. A total of 64 specimens [Sputum (n= 28) and Endotracheal aspirate (ET, n=36)] were cultured on MacConkey’s agar and Blood agar and further species identification with Antimicrobial Susceptibility Pattern was done by automated Vitek-2 compact system. Ventilator-associated Pneumonia (VAP) was found in 14.6% of infected patients, with male predominance and common in the 30-50 years age group. Out of them, 72% were mainly associated with late-onset. Overall, the major isolates were (20/64, 31%), followed by (19/64, 29.6%) and (17/64, 26.5%) both as solitary and mixed infections.76% strains of and 85% of strains were resistant to carbapenems and 93.3% of were resistant to cephalosporins and carbapenems. strains were 100% resistant to carbapenems. The study recommends effective Infection control practices and strong antibiotic stewardship programs to reduce the morbidity and mortality of nosocomial pneumonia.

Pneumonia due to silent aspiration: a diagnostic and therapeutic challenge

Aspiration pneumonia (AP) may present as gross aspiration of large gastric contents or as a consequence of silent aspiration of contaminated oropharyngeal secretions.AP due to silent aspiration is caused by dysphagia and, in some instances, impaired cough reflex. Factors favouring the development of pneumonia include advanced age as well as severe comorbidity and impaired functional status.Therefore, silent aspiration is a frequent etiology of community-acquired pneumonia in aged patients but also of nosocomial pneumonia. Recurrent pneumonia should always prompt the consideration of AP.Treatment of acute AP should include not only the use of antimicrobial agents but also chest physiotherapy and airway clearance techniques. In addition, all patients with silent aspiration and AP should be subject to an investigation of swallowing function and, in the presence of dysphagia, also receive treatment for this condition. This includes methods of restitution, compensation and adaptation of impaired swallowing function.

A phase III randomized controlled non-inferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) versus piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP).

Imipenem/cilastatin/relebactam (IMI/REL) is a β-lactam/β-lactamase inhibitor combination effective against gram-negative pathogens. Efficacy and safety of IMI/REL were studied in critically ill adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). In this phase III, double-blind, multinational, randomized trial (NCT03583333), adults with HABP/VABP were randomized 1:1 to receive intravenous IMI/REL (500 mg/250 mg) or piperacillin/tazobactam (PIP/TAZ; 4000 mg/500 mg) every 6 h for 7-14 days. The primary endpoint was 28-day all-cause mortality (ACM). Secondary endpoints were clinical response (CR), microbiological response (MR), and adverse event (AE) incidence. In the modified intention-to-treat population (N = 270 [IMI/REL: n = 134; PIP/TAZ: n = 136]), demographics and baseline characteristics were comparable between treatment groups. Most patients were from China. IMI/REL was non-inferior to PIP/TAZ for 28-day ACM (11.2% vs 5.9%; adjusted difference [95% confidence interval]: 5.2% [-1.5 to 12.4]). Secondary outcomes were comparable between treatment groups, including favorable CR and MR. AEs resulting in death were generally consistent with pre-existing or underlying illness. IMI/REL met non-inferiority criteria versus PIP/TAZ for 28-day ACM, and safety profiles were comparable. This trial could support the use of IMI/REL to treat adults with HABP/VABP, including regional use in China.

Development and validation of interpretable machine learning models for postoperative pneumonia prediction.

Postoperative pneumonia, a prevalent form of hospital-acquired pneumonia, poses significant risks to patients' prognosis and even their lives. This study aimed to develop and validate a predictive model for postoperative pneumonia in surgical patients using nine machine learning methods. Our study aims to develop and validate a predictive model for POP in surgical patients using nine machine learning algorithms. By evaluating the performance differences among these machine learning models, this study aims to assist clinicians in early prediction and diagnosis of POP, providing optimal interventions and treatments. Retrospective data from electronic medical records was collected for 264 patients diagnosed with postoperative pneumonia and 264 healthy control surgical patients. Through correlation screening, chi-square tests, and feature importance ranking, 47 variables were narrowed down to 5 potential predictive factors based on the main cohort of 528 patients. Nine machine learning models, including k-nearest neighbors, support vector machine, random forest, decision tree, gradient boosting machine, adaptive boosting, naive bayes, general linear model, and linear discriminant analysis, were developed and validated to predict postoperative pneumonia. Model performance was evaluated using the area under the receiver operating curve, sensitivity, specificity, accuracy, precision, recall, and F1 score. A distribution plot of feature importance and feature interaction was obtained to interpret the machine learning models. Among 17,190 surgical patients, 264 (1.54%) experienced postoperative pneumonia, which resulted in adverse outcomes such as prolonged hospital stay, increased ICU admission rates, and mortality. We successfully established nine machine learning models for predicting postoperative pneumonia in surgical patients, with the general linear model demonstrating the best overall performance. The AUC of the general linear model on the testing set was 0.877, with an accuracy of 0.82, specificity of 0.89, sensitivity of 0.74, precision of 0.88, and F1 score of 0.80. Our study revealed that the duration of bed rest, unplanned re-operation, end-tidal CO2, postoperative albumin, and chest X-ray film were significant predictors of postoperative pneumonia. Our study firstly demonstrated that the general linear model based on 5 common variables might predict postoperative pneumonia in the general surgical population.

Nosocomial Pneumonia in Georgia: A Study of Extended Spectrum Beta-Lactamase (ESBL)-Producing Versus Non-extended ESBL Gram-Negative Bacterial Profiles.

Nosocomial pneumonia is a significant healthcare challenge, particularly in the face of rising antimicrobial resistance among Gram-negative bacteria. The production of extended spectrum beta-lactamase (ESBL) exacerbates treatment complexities. This study investigates the prevalence and resistance patterns of ESBL-producing and non-ESBL Gram-negative bacteria in nosocomial pneumonia cases in Georgian hospitals to inform antibiotic stewardship and treatment strategies. To our knowledge, this is the first study of its kind conducted in Georgia, offering critical insights into bacterial resistance in this region. This prospective observational study analyzed a total of 357 pulmonary samples from patients diagnosed with nosocomial pneumonia in Georgian hospitals between December 2022 and February 2024. Gram-negative bacterial identification and ESBL determination were performed using the combination disk method, adhering to European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. The analyses were conducted at TEST-IMP Laboratory and the Richard Lugar Center for Public Health Research to investigate the prevalence and resistance patterns of ESBL-producing versus non-ESBL Gram-negative bacteria. Among the 256 Gram-negative isolates, 201 (78.5%) were ESBL producers. Pseudomonas aeruginosa (63.7%), Acinetobacter baumannii (18.4%), and Klebsiella pneumoniae (17.9%) were the most prevalent. Non-ESBL producers accounted for 21.5% but exhibited notable beta-lactamase activity. The remaining 101 samples were evaluated as an additional analysis, revealing the distribution of Gram-positive bacteria and fungi as outlined in the results. However, the primary emphasis of this study remains on the resistance patterns and prevalence of Gram-negative pathogens. The study highlights a concerning prevalence of ESBL-producing bacteria in nosocomial pneumonia cases, emphasizing the urgent need for improved antibiotic stewardship and infection control practices in Georgian hospitals. Non-ESBL producers displayed susceptibility to advanced antibiotics, presenting potential therapeutic opportunities, though vigilance is required to prevent further resistance development.

Ex vivo assessment of sulbactam-durlobactam clearance during continuous renal replacement therapy to guide dosing recommendations.

Sulbactam-durlobactam is approved for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex. Patients with serious Acinetobacter infections may require support with continuous renal replacement therapy (CRRT), which presents challenges for optimal dosing of antibiotics. Sulbactam-durlobactam dosing regimens were derived for this population using an ex vivo CRRT model and Monte Carlo simulation (MCS). Transmembrane clearance (CLTM) was determined in hemofiltration (CVVH) and hemodialysis (CVVHD) modes using the Prismaflex M100 and HF1400 hemofilter sets and with effluent rates of 1, 2, and 3 L/h. Pre-filter, post-filter blood, and effluent samples were collected over 60 min to calculate sieving (SC) and saturation (SA) coefficients for CVVH and CVVHD, respectively. An established population pharmacokinetic model was integrated with the CLTM; then, a 1,000 patient MCS was conducted to determine exposures of potential dosing regimens. Adsorption and degradation in the ex vivo CRRT model were negligible. The overall mean ± standard deviation SC/SA was 1.14 ± 0.12 and 0.93 ± 0.08 for sulbactam and durlobactam, respectively. In multivariable regression analyses, effluent rate was the primary driver of CLTM for both drugs. For effluent rates <3 L/h, sulbactam-durlobactam 1 g-1g q8h as 3 h infusion achieved a high probability of pharmacodynamic target attainment while retaining area under the curve exposures consistent with the standard dose in non-CRRT patients. For effluent rates ≥3 to 5 L/h, the optimal regimen was 1 g-1g q6h 3 h infusion. Sulbactam-durlobactam regimens that provide optimum drug exposures for efficacy and safety were identified for CRRT based on the prescribed effluent rate.

Ceftobiprole Medocaril: A New Fifth-Generation Cephalosporin.

The objective was to review the pharmacology, efficacy, and safety of intravenous ceftobiprole in the treatment of bloodstream infections, acute bacterial skin and skin structure infections (ABSSSIs), community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP), or ventilator-associated pneumonia (VAP). PubMed and ClinicalTrials.gov were searched using the following terms: ceftobiprole, ceftobiprole medocaril, ceftobiprole medocaril sodium, Zevtera, and BAL5788. Articles published in English between January 1985 and August 15, 2024, related to pharmacology, safety, efficacy, and clinical trials were reviewed. Ceftobiprole has shown similar efficacy to comparator antibiotics in CAP, ABSSSIs, and bloodstream infections. Overall treatment success in patients with bacteremia was 69.8% and 68.7%; 91.3% and 88.1% with ABSSSIs and 86.6% and 87.4% with CAP in ceftobiprole and comparator groups, respectively. Finally, in the management of HAP and VAP, ceftobiprole was inferior in the VAP population. Ceftobiprole had a favorable safety profile with gastrointestinal adverse effects occurring more frequently than comparators. Clinicians have limited options to treat multidrug-resistant infections. Ceftobiprole has demonstrated efficacy against causative pathogens in specific infections including methicillin-resistant Staphylococcus aureus bacteremia (SAB), ABSSSI, and CAP and may be considered a viable alternative. However, ceftobiprole's impact on HAP, VAP, and febrile neutropenia needs to be further delineated. Ceftobiprole's broad-spectrum activity makes it a viable option for treating patients hospitalized with CAP, ABSSSI, and SAB. Further studies are needed in severely ill HAP or VAP, febrile neutropenia, and pediatric patients.

Evaluation of a Pharmacist-Led Methicillin-Resistant Staphylococcus aureus Nasal PCR Testing Protocol.

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) can cause cases of community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, and nasal colonization with this pathogen increases the risk of infection. Due to its high negative predictive value, multiple studies support using the MRSA nasal polymerase chain reaction (PCR) test to discontinue antimicrobials that target MRSA in the setting of a negative test result. The purpose of this project was to assess the utility of a protocol to allow pharmacists the ability to order MRSA nasal PCR screenings in hospitalized patients with pneumonia. Results: The pre-protocol group included a random sample of 100 patients, and the post-protocol group included 625 patients. Vancomycin DOTs when pharmacists ordered PCRs were significantly lower compared to the pre-protocol group (p < 0.5; 95% CI, 0.46-2.24). The average length of stay and readmission rates at 30 days were significantly lower in the post-protocol group compared to the pre-protocol group (p < 0.05 and p = 0.02, respectively), but there was no significant difference in mortality (p = 0.33). Methods: A protocol was implemented at our institution that allowed pharmacists to order an MRSA nasal PCR test in patients with pneumonia. This retrospective chart review compared a cohort of patients who received vancomycin from before implementation of the protocol to patients who received vancomycin after the protocol's implementation. The primary endpoint was vancomycin days of therapy (DOTs) between the pre-protocol group and the post-protocol group. Other endpoints assessed included the length of hospitalization, readmission rates, and mortality. Conclusions: Pharmacists ordering MRSA nasal PCR tests significantly reduced vancomycin DOTs, average length of stay, and 30-day readmission rates, contributing to positive outcomes in patients with pneumonia.

Bacteremic nosocomial pneumonia caused by Gram-negative bacilli: results from the nationwide ALARICO study in Italy.

To describe the clinical characteristics and outcomes of patients with nosocomial pneumonia (NP) causedby carbapenem-resistant Gram-negative bacilli (CR-GNB) and to compare them to patients with NP causedby carbapenem-susceptible (CS)-GNB. Prospective observational multicenter study including patients with bacteremic NP caused by GNB from the ALARICO Network (June 2018-January 2020). The primary outcome measure was 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated. Overall, 167 patients with GNB NP were included: 101 with bacteremic NP causedby CR-GNB (n = 39 by KPC-producing Klebsiella pneumoniae, n = 29 by carbapenem-resistant Acinetobacter baumannii, n = 28 by carbapenem-resistant Pseudomonas aeruginosa, n = 5 by MBL-producing Klebsiella pneumoniae) and 66 cases of bacteremic CS-GNB NP. Thirty-day mortality rate was higher in patients with NP causedby CR-GNB compared to those with NPcausedby CS-GNB (46.5% vs 30.3%, p = 0.036). On multivariable analysis, age (HR 1.044, 95% CI 1.021-1.067, p < 0.001), hematological malignancy (HR 4.307, 95% CI 1.924-9.643, p < 0.001) and septic shock (HR 3.668, 95% CI 2.001-6.724, p < 0.001) were factors independently associated with 30-day mortality, while the receipt of adequate antibiotic therapy within 24h from infection onset (HR 0.495, 95% CI 0.252-0.969, p = 0.04) was a protective factor. Carbapenem resistance was not associated with increased risk of mortality (HR 1.075, 95% CI 0.539-2.142, p = 0.837). Patients with bacteremic NP causedby CR-GNB have high mortality rate. Strategies to reduce the time from infection to the administration of adequate antibiotic therapy should be implemented in patients with NP.