Etiology of bacterial pneumonia and multi-drug resistance pattern among pneumonia suspected patients in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Bacterial pneumonia can affect all age groups, but people with weakened immune systems, young children, and the elderly are at a higher risk. Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa are the most common causative agents of pneumonia, and they have developed high MDR in recent decades in Ethiopia. This systematic review and meta-analysis aimed to determine the pooled prevalence of bacterial pneumonia and multidrug resistance in Ethiopia. METHODS: The articles were searched extensively in the electronic databases and grey literature using entry terms or phrases. Studies meeting the eligibility criteria were extracted in MS Excel and exported for statistical analysis into STATA version 14 software. The pooled prevalence of bacterial pneumonia and multidrug resistance were calculated using a random-effects model. Heterogeneity was assessed by using the I2 value. Publication bias was assessed using a funnel plot and Egger's test. A sensitivity analysis was done to assess the impact of a single study on the pooled effect size. RESULT: Of the 651 studies identified, 87 were eligible for qualitative analysis, of which 11 were included in the meta-analysis consisting of 1154 isolates. The individual studies reported prevalence of bacterial pneumonia ranging from 6.19 to 46.3%. In this systematic review and metanalysis, the pooled prevalence of bacterial pneumonia in Ethiopia was 37.17% (95% CI 25.72-46.62), with substantial heterogeneity (I2 = 98.4%, p < 0.001) across the studies. The pooled prevalence of multidrug resistance in bacteria isolated from patients with pneumonia in Ethiopia was 67.73% (95% CI: 57.05-78.40). The most commonly isolated bacteria was Klebsiella pneumoniae, with pooled prevalence of 21.97% (95% CI 16.11-27.83), followed by Streptococcus pneumoniae, with pooled prevalence of 17.02% (95% CI 9.19-24.86), respectively. CONCLUSION: The pooled prevalence of bacterial isolates from bacterial pneumonia and their multidrug resistance were high among Ethiopian population. The initial empirical treatment of these patients remains challenging because of the strikingly high prevalence of antimicrobial resistance.

Lung ultrasound and procalcitonin, improving antibiotic management and avoiding radiation exposure in pediatric critical patients with bacterial pneumonia: a randomized clinical trial.

BACKGROUND: Pneumonia is a major public health problem with an impact on morbidity and mortality. Its management still represents a challenge. The aim was to determine whether a new diagnostic algorithm combining lung ultrasound (LUS) and procalcitonin (PCT) improved pneumonia management regarding antibiotic use, radiation exposure, and associated costs, in critically ill pediatric patients with suspected bacterial pneumonia (BP). METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children < 18y with suspected BP admitted to the PICU from September 2017 to December 2019, were included. PCT was determined at admission. Patients were randomized into the experimental group (EG) and control group (CG) if LUS or chest X-ray (CXR) were done as the first image test, respectively. Patients were classified: 1.LUS/CXR not suggestive of BP and PCT < 1 ng/mL, no antibiotics were recommended; 2.LUS/CXR suggestive of BP, regardless of the PCT value, antibiotics were recommended; 3.LUS/CXR not suggestive of BP and PCT > 1 ng/mL, antibiotics were recommended. RESULTS: 194 children were enrolled, 113 (58.2%) females, median age of 134 (IQR 39-554) days. 96 randomized into EG and 98 into CG. 1. In 75/194 patients the image test was not suggestive of BP with PCT < 1 ng/ml; 29/52 in the EG and 11/23 in the CG did not receive antibiotics. 2. In 101 patients, the image was suggestive of BP; 34/34 in the EG and 57/67 in the CG received antibiotics. Statistically significant differences between groups were observed when PCT resulted < 1 ng/ml (p = 0.01). 3. In 18 patients the image test was not suggestive of BP but PCT resulted > 1 ng/ml, all of them received antibiotics. A total of 0.035 mSv radiation/patient was eluded. A reduction of 77% CXR/patient was observed. LUS did not significantly increase costs. CONCLUSIONS: Combination of LUS and PCT showed no risk of mistreating BP, avoided radiation and did not increase costs. The algorithm could be a reliable tool for improving pneumonia management. CLINICAL TRIAL REGISTRATION: NCT04217980.

Cost-effectiveness analysis of CTZ/TAZ for the treatment of ventilated hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia in Japan.

BACKGROUND: Resistant bacterial infections, particularly those caused by gram-negative pathogens, are associated with high mortality and economic burdens. Ceftolozane/tazobactam demonstrated efficacy comparable to meropenem in patients with ventilated hospital-acquired bacterial pneumonia in the ASPECT-NP study. One cost-effectiveness analysis in the United States revealed that ceftolozane/tazobactam was cost effective, but no Japanese studies have been conducted. Therefore, the objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam compared to meropenem for patients with ventilated hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia from a health care payer perspective. METHODS: A hybrid decision-tree Markov decision-analytic model with a 5-year time horizon were developed to estimate costs and quality-adjusted life-years and to calculate the incremental cost-effectiveness ratio associated with ceftolozane/tazobactam and meropenem in the treatment of patients with ventilated hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. Clinical outcomes were based on the ASPECT-NP study, costs were based on the national fee schedule of 2022, and utilities were based on published data. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to assess the robustness of our modeled estimates. RESULTS: According to our base-case analysis, compared with meropenem, ceftolozane/tazobactam increased the total costs by 424,731.22 yen (£2,626.96) and increased the quality-adjusted life-years by 0.17, resulting in an incremental cost-effectiveness ratio of 2,548,738 yen (£15,763.94) per quality-adjusted life-year gained for ceftolozane/tazobactam compared with meropenem. One-way sensitivity analysis showed that although the incremental cost-effectiveness ratio remained below 5,000,000 yen (£30,925) for most of the parameters, the incremental net monetary benefit may have been less than 0 depending on the treatment efficacy outcome, especially the cure rate and mortality rate for MEPM and mortality rate for CTZ/TAZ. 53.4% of the PSA simulations demonstrated that CTZ/TAZ was more cost-effective than MEPM was. CONCLUSION: Although incremental cost-effectiveness ratio was below ï¿¥5,000,000 in base-case analysis, whether ceftolozane/tazobactam is a cost-effective alternative to meropenem for ventilated hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia in Japan remains uncertain. Future research should examine the unobserved heterogeneity across patient subgroups and decision-making settings, to characterise decision uncertainty and its consequences so as to assess whether additional research is required.

In vitro modelling of bacterial pneumonia: a comparative analysis of widely applied complex cell culture models.

Bacterial pneumonia greatly contributes to the disease burden and mortality of lower respiratory tract infections among all age groups and risk profiles. Therefore, laboratory modelling of bacterial pneumonia remains important for elucidating the complex host-pathogen interactions and to determine drug efficacy and toxicity. In vitro cell culture enables for the creation of high-throughput, specific disease models in a tightly controlled environment. Advanced human cell culture models specifically, can bridge the research gap between the classical two-dimensional cell models and animal models. This review provides an overview of the current status of the development of complex cellular in vitro models to study bacterial pneumonia infections, with a focus on air-liquid interface models, spheroid, organoid, and lung-on-a-chip models. For the wide scale, comparative literature search, we selected six clinically highly relevant bacteria (Pseudomonas aeruginosa, Mycoplasma pneumoniae, Haemophilus influenzae, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Staphylococcus aureus). We reviewed the cell lines that are commonly used, as well as trends and discrepancies in the methodology, ranging from cell infection parameters to assay read-outs. We also highlighted the importance of model validation and data transparency in guiding the research field towards more complex infection models.

Characterization and Determinants of Long-Term Immune Recovery Under Suppressive Antiretroviral Therapy.

OBJECTIVE: We developed a robust characterization of immune recovery trajectories in people living with HIV on antiretroviral treatment (ART) and relate our findings to epidemiological risk factors and bacterial pneumonia. METHODS: Using data from the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Cohort Study (n = 5907), we analyzed the long-term trajectories of CD4 cell and CD8 cell counts and their ratio in people living with HIV on ART for at least 8 years by fitting nonlinear mixed-effects models. The determinants of long-term immune recovery were investigated using generalized additive models. In addition, prediction accuracy of the modeled trajectories and their impact on the fit of a model for bacterial pneumonia was assessed. RESULTS: Overall, our population showed good immune recovery (median plateau [interquartile range]-CD4: 718 [555-900] cells/µL, CD8: 709 [547-893] cells/µL, CD4/CD8: 1.01 [0.76-1.37]). The following factors were predictive of recovery: age, sex, nadir/zenith value, pre-ART HIV-1 viral load, hepatitis C, ethnicity, acquisition risk, and timing of ART initiation. The fitted models proved to be an accurate and efficient way of predicting future CD4 and CD8 cell recovery dynamics: Compared with carrying forward the last observation, mean squared errors of the fitted values were lower by 1.3%-18.3% across outcomes. When modeling future episodes of bacterial pneumonia, using predictors derived from the recovery dynamics improved most model fits. CONCLUSION: We described and validated a method to characterize individual immune recovery trajectories of people living with HIV on suppressive ART. These trajectories accurately predict long-term immune recovery and the occurrence of bacterial pneumonia.

Evaluation of the effect of therapeutic durations on small ruminant bacterial pneumonia.

BACKGROUND: Sheep and goat production in Ethiopia is hindered by numerous substandard production systems and various diseases. Respiratory disease complexes (RDC) pose a significant threat to the productivity of these animals. Pneumonia is a common manifestation of respiratory disease complexes and often necessitates a prolonged course of antibiotic treatment. This study aimed to optimize and propose the ideal duration of therapy for pneumonia in sheep and goats. METHODS: The study was conducted from February to June 2021 at the Veterinary Teaching Hospital of the College of Veterinary Medicine and Agriculture, Addis Ababa University. The study recruited 54 sheep and goats presented to the hospital for treatment with a confirmed RDC as determined based on clinical signs and bacteriological methods. The animals were randomly allocated to 5 groups each group receiving 10% oxytetracycline (Phenxyl, Phenix, Belgum) intramuscularly for a duration of 3, 4, 5, 6 and 7 consecutive days. The treatment outcomes were assessed by recording vital signs (body temperature, respiratory rate, heart rate, coughing, and nasal discharges), performing lung ultrasonography (L-USG) as well as collection of nasal swabs for bacterial isolation and molecular identification before and after completion of the treatment. An ordered logistic regression model with random effects was employed to determine the optimal therapeutic duration, taking into account the cumulative scores of the outcome variables across the different groups. RESULTS: Among the 54 sheep and goats treated with 10% oxytetracycline, a total of 74.07% (95% CI, 60.35-85.04) achieved complete recovery, as confirmed through clinical, ultrasound, and bacteriological methods. In Group 1 (G1), out of 12 sheep and goats, 8 (83.0%) recovered completely; in Group 2 (G2), out of 11 animals, 9 (82.0%) recovered completely; in Group 3 (G3), out of 11 animals, 10 (93.0%) recovered completely; in Group 4 (G4), out of 9 animals, 9 (100.0%) recovered completely; and in Group 5 (G5), out of 11 animals, 10 (91.0%) recovered completely. Bacteriological examination of nasal swabs indicated involvement of M. hemolytica in 27 (50.00%) and P. multocida in 13 (24.07%) of pneumonic animals. Detection of specific marker genes confirmed only five of the presumptive M. hemolytica isolates, whilst no isolates tested positive for P. multocida. Post-treatment samples collected from recovered animals did not yield any M. hemolytica nor P. multocida. Based on results from clinical signs, L-USG, and bacterial infection variables, the group of sheep and goats treated for seven consecutive days (G5) showed the highest recovery score compared to the other groups, and there was a statistically significant difference (coefficient (ß) = - 2.296, p = 0.021) in variable score between G5 and G1. These findings suggest that the administration of 10% oxytetracycline for a full course of seven consecutive days resulted in symptomatic and clinical recovery rates from respiratory disease in sheep and goats.

Community-acquired bacterial pneumonia in children: an update on antibiotic duration and immunization strategies.

PURPOSE OF REVIEW: This review is structured to update clinicians on the epidemiology, antibiotic treatment, and prevention of pediatric bacterial pneumonia. The review provides information regarding the current research on antibiotic management for bacterial pneumonia and the newest immunization recommendations to prevent pneumococcal pneumonia and other respiratory infections. RECENT FINDINGS: The recommended length of antibiotic therapy for bacterial pneumonia has been discrepant between low-income and high-income countries. Recently, randomized controlled trials conducted in high-income countries provided evidence to support a short antibiotic course (3-5 days) for uncomplicated bacterial pneumonia in otherwise healthy children. The negative impact of inaccurate penicillin allergy labels in children with pneumonia has emphasized the importance of prompt allergy de-labeling. Newer pneumococcal vaccines are recommended for children and are expected to have a significant impact on bacterial pneumonia rates. SUMMARY: Pediatric bacterial pneumonia is an important contributor to childhood morbidity and mortality. A short antibiotic course seems to be sufficient for the outpatient management of uncomplicated bacterial pneumonia; however, more studies are required in the inpatient setting. Future studies will inform the impact of recently introduced pneumococcal and respiratory syncytial virus vaccines on the epidemiology of bacterial pneumonia.

Target attainment of intravenous lefamulin for treatment of acute bacterial skin and skin structure infections.

OBJECTIVES: Lefamulin is a pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). Its spectrum of activity, good penetration into soft tissues and low rates of cross-resistance also make lefamulin a potentially valuable option for treatment of acute bacterial skin and skin structure infections (ABSSSIs). A Phase 2 trial of lefamulin for ABSSSI indicated similar efficacy of 100 and 150 mg q12h IV dosing regimens. In the present study, the potential of lefamulin for this indication was further evaluated from a translational pharmacokinetic/pharmacodynamic perspective. METHODS: PTA was determined for various dosages using Monte Carlo simulations of a population pharmacokinetic model of lefamulin in ABSSSI patients and preclinical exposure targets associated with bacteriostasis and a 1-log reduction in bacterial count. Overall target attainment against MSSA and MRSA was calculated using lefamulin MIC distributions. RESULTS: Overall attainment of the bacteriostasis target was 94% against MSSA and 84% against MRSA for the IV dosage approved for CABP (150 mg q12h). Using the same target, for the 100 mg q12h regimen, overall target attainment dropped to 68% against MSSA and 50% against MRSA. Using the 1-log reduction target, overall target attainment for both regimens was <40%. CONCLUSIONS: Lefamulin at the currently approved IV dosage covers most Staphylococcus aureus isolates when targeting drug exposure associated with bacteriostasis, suggesting potential of lefamulin for the treatment of ABSSSIs. Lefamulin may not be appropriate in ABSSSI when rapid bactericidal activity is warranted.

Pseudomonas fluorescens pneumonia.

Pseudomonas fluorescens (P. fluorescens) is not generally considered a bacterial pathogen in humans; however, multiple culture-based and culture-independent studies have identified it in the indigenous microbiota of multiple body sites. We herein report a rare case of pneumonia caused by P. fluorescens. A man in his 80 s with chronic obstructive pulmonary disease and diabetes mellitus was diagnosed with stage II rectal cancer. He underwent laparoscopic surgery, and on the 6th postoperative day, he developed a high fever. Chest computed tomography revealed infiltration in the left lower lung. Gram staining of the sputum showed Gram-negative rods phagocytosed by neutrophils, suggesting postoperative nosocomial pneumonia. The patient was started on tazobactam/piperacillin, and his pneumonia quickly improved. Later, only P. fluorescens was detected in a sputum culture. It was susceptible to common antipseudomonal agents. Gram staining of P. fluorescens appears to show a slightly thicker and larger morphology in comparison to Pseudomonas aeruginosa. Although there have been reports of opportunistic infections caused by P. fluorescens in immunosuppressed patients, including those with advanced cancer, most have been bloodstream infections, with very few reports of pneumonia alone. Clinicians should be aware that patients, who are not necessarily immunosuppressed, may develop pneumonia caused by P. fluorescens.

Achromobacter pneumonia in a patient with advanced COPD, a diagnostic challenge.

Bacterial pneumonia causes significant morbidity and mortality especially in elderly and immunocompromised hosts. Achromobacter xylosoxidans denitrificans pneumonia is very rarely reported. However, the reported cases have been in patients who are either immunocompromised or have bronchiectasis. We hereby present a unique case of Achromobacter xylosoxidans denitrificans pneumonia in an immunocompetent patient with advanced chronic obstructive pulmonary disease (COPD). Our patient is a Caucasian male admitted with shortness of breath, fever and cough. Chest X-ray demonstrated right-sided infiltrates and he was treated with intravenous ceftriaxone and azithromycin. He was discharged home on oral amoxicillin-clavulanate 875-125 mg two times per day for a total of 7 days. Patient returned to emergency room after 5 weeks with persistent symptoms and chest X-ray revealed persistent right-sided infiltrate and sputum culture showed Achromobacter xylosoxidans denitrificans. The patient was started on oral levofloxacin 750 mg one time per day for 2 weeks with resolution of symptoms.

Which trial do we need? Combination antimicrobial therapy for hospital-acquired bacterial pneumonia caused by Pseudomonas aeruginosa.

Meropenem therapy will be open-label, while tobramycin or placebo will be administered in a double-blind fashion. The primary trial endpoint will be a composite hierarchical outcome of 1) 28-day all-cause mortality, 2) ventilator-free days, and 3) modified time to clinical stability, evaluated using a win ratio methodology (see below). Secondary trial outcomes will include frequency of safety events (acute kidney injury), resolution of circulatory shock, recurrent HABP, and emergence of meropenem resistance both during treatment and in cases of recurrent infection. Using simulation studies to inform sample size calculations, we estimate that recruitment of 130 patients per treatment arm would provide at least 80% power to detect a win ratio of 1.50 while preserving a two-sided type 1 error rate of 0.05.

Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia.

BACKGROUND: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation. METHODS: A multidisciplinary committee created an infectious diseases DOOR endpoint customized for HABP/VABP, incorporating infectious complications, serious adverse events, and mortality. We applied this to 2 previously completed, large randomized controlled trials for HABP/VABP. ZEPHyR compared vancomycin to linezolid and VITAL compared linezolid to tedizolid. For each trial, we evaluated the DOOR distribution and probability, including DOOR component and partial credit analyses. We also applied DOOR in subgroup analyses. RESULTS: In both trials, the HABP/VABP DOOR demonstrated similar overall clinical outcomes between treatment groups. In ZEPHyR, the probability that a participant treated with linezolid would have a more desirable outcome than a participant treated with vancomycin was 50.2% (95% confidence interval [CI], 45.1%--55.3%). In VITAL, the probability that a participant treated with tedizolid would have a more desirable outcome than a participant treated with linezolid was 48.7% (95% CI, 44.8%-52.6%). The DOOR component analysis revealed that participants treated with tedizolid had a less desirable outcome than those treated with linezolid when considering clinical response alone. However, participants with decreased renal function had improved overall outcomes with tedizolid. CONCLUSIONS: The HABP/VABP DOOR provided more granular information about clinical outcomes than is typically presented in clinical trials. HABP/VABP trials would benefit from prospectively using DOOR.

Bacterial pneumonia-induced shedding of epithelial heparan sulfate inhibits the bactericidal activity of cathelicidin in a murine model.

Bacterial pneumonia is a common clinical syndrome leading to significant morbidity and mortality worldwide. In the current study, we investigate a novel, multidirectional relationship between the pulmonary epithelial glycocalyx and antimicrobial peptides in the setting of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Using an in vivo pneumonia model, we demonstrate that highly sulfated heparan sulfate (HS) oligosaccharides are shed into the airspaces in response to MRSA pneumonia. In vitro, these HS oligosaccharides do not directly alter MRSA growth or gene transcription. However, in the presence of an antimicrobial peptide (cathelicidin), increasing concentrations of HS inhibit the bactericidal activity of cathelicidin against MRSA as well as other nosocomial pneumonia pathogens (Klebsiella pneumoniae and Pseudomonas aeruginosa) in a dose-dependent manner. Surface plasmon resonance shows avid binding between HS and cathelicidin with a dissociation constant of 0.13 µM. These findings highlight a complex relationship in which shedding of airspace HS may hamper host defenses against nosocomial infection via neutralization of antimicrobial peptides. These findings may inform future investigation into novel therapeutic targets designed to restore local innate immune function in patients suffering from primary bacterial pneumonia.NEW & NOTEWORTHY Primary Staphylococcus aureus pneumonia causes pulmonary epithelial heparan sulfate (HS) shedding into the airspace. These highly sulfated HS fragments do not alter bacterial growth or transcription, but directly bind with host antimicrobial peptides and inhibit the bactericidal activity of these cationic polypeptides. These findings highlight a complex local interaction between the pulmonary epithelial glycocalyx and antimicrobial peptides in the setting of bacterial pneumonia.

Childhood community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a common disease in children, and its aetiological and clinical diagnosis are challenging for physicians in both private practice and hospitals. Over the past three decades, conjugate vaccines have successfully reduced the burden of the former main causes of CAP, Streptococcus pneumoniae and Haemophilus influenzae type b. Today, viruses are by far the most commonly detected pathogens in children with CAP.  Conclusion: New insights into the aetiology and treatment of CAP in children in recent years have influenced management and are the focus of this review. In addition to reducing diagnostic uncertainty, there is an urgent need to reduce antibiotic overuse and antimicrobial resistance in children with CAP. What is Known: • Conjugate vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b have shifted the epidemiology of childhood CAP to predominantly viral pathogens and Mycoplasma pneumoniae. • Clinical, laboratory, and radiological criteria cannot reliably distinguish between bacterial and viral aetiology in children with CAP. What is New: • Test results and epidemiological data must be carefully interpreted, as no single diagnostic method applied to non-pulmonary specimens has both high sensitivity and high specificity for determining pneumonia aetiology in childhood CAP. • This review provides a simple and pragmatic management algorithm for children with CAP to aid physicians in providing optimal and safe care and reducing antibiotic prescribing.

Exploring the microbial landscape: uncovering the pathogens associated with community-acquired pneumonia in hospitalized patients.

Objectives: This study aimed to investigate the etiology, clinical features, and outcomes of community-acquired pneumonia (CAP) in adults. Understanding the causative pathogens is essential for effective treatment and prevention. Design: Between 2016-2018, 518 hospitalized adults with CAP and 241 controls without symptoms were prospectively enrolled. Urine samples were collected for pneumococcal urinary antigen tests and nasopharyngeal swabs for viral and bacterial analysis, combined with routine diagnostic care. Results: Among the included CAP patients, Streptococcus pneumoniae was the most common pathogen, detected in 28% of patients, followed by Haemophilus influenzae in 16%. Viruses were identified in 28%, and concurrent viruses and bacteria were detected in 15%. There was no difference in mortality, length of stay, or symptoms at hospitalization when comparing patients with bacterial, viral, or mixed etiologies. Among the control subjects without respiratory symptoms, S. pneumoniae, H. influenzae, or Moraxella catarrhalis were detected in 5-7%, and viruses in 7%. Conclusion: Streptococcus pneumoniae emerged as the predominant cause of CAP, followed closely by viruses and H. influenzae. Intriguingly, symptoms and outcome were similar regardless of etiology. These findings highlight the complexity of this respiratory infection and emphasize the importance of comprehensive diagnostic and treatment strategies.Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT03606135].

Therapeutic Effect and Safety Evaluation of Naringin on Klebsiella pneumoniae in Mice.

Critically ill patients with Corona Virus Disease 2019 (COVID-19) often develop secondary bacterial infections that pose a significant threat to patient life safety, making the development of drugs to prevent bacterial infections in the lungs critical to clinical care. Naringin (NAR) is one of the significant natural flavonoids rich in Pummelo Peel (Hua Ju Hong), with anti-inflammatory, antimicrobial, and antioxidant activities, and is commonly used in treating respiratory tract infectious diseases. In this study, the in vitro and in vivo findings revealed that, after Klebsiella pneumoniae (Kpn) infection, NAR inhibited overactivation of the nuclear factor kappa-B(NF-κB) signaling pathway in alveolar macrophages of mice, reduced neutrophil (NEs) recruitment, and lowered the induced production of proinflammatory markers, such as Interleukin-6(IL-6) and tumor necrosis factor α(TNF-α). Thus, it suppressed excessive immune responses in the lungs, as well as attenuated the induced pulmonary fibrosis and inflammatory infiltrates. These results suggest that NAR has a preventive effect against Kpn in mice. In addition, the study evaluated NAR's potential toxicity, demonstrating that NAR is safe at effective doses. These results suggested that NAR effectively reduces excessive inflammatory damage in the lungs induced by Kpn and enhances the body's ability to clear bacteria. Therefore, NAR may be an effective and safe healthcare drug for preventing and caring for bacterial pneumonia.

Clinical characteristics and risk factors associated with secondary bacterial pneumonia among COVID-19 patients in ICU.

INTRODUCTION: COVID-19 and secondary infections developing during COVID-19 follow-up are one of the most important causes of morbidity and mortality in intensive care units (ICU). In this study, we aimed to determine the frequency, microbiology, risk factors, and outcomes of secondary bacterial pneumonia in hospitalized patients due to COVID-19. METHODOLOGY: We studied all patients with bacterial pneumonia developed in patients with severe COVID-19 infection in the COVID-19 intensive care unit in a single-center hospital between March 16, 2020 and June 17, 2020. Patients hospitalized and followed up in the ICU for respiratory failure were examined in terms of secondary infection affecting morbidity and mortality. RESULTS: Ninety-six (20%) of 471 patients had secondary bacterial pneumonia, respectively; of the leading pathogens were Acinetobacter baumannii (44.8%) and Klebsiella pneumoniae (39.6%), followed by Pseudomonas aeruginosa (4.2%), Escherichia coli (3.1%), methicillin-resistant Staphylococcus aureus (MRSA) (3.1%), Streptococcus pneumoniae (3.1%), and Methicillin-susceptible Staphylococcus aureus (MSSA) (1%). The mortality rate among infected (75% / 47.5%) was significantly higher than in uninfected patients. Associated with the development of secondary bacterial pneumonia in COVID-19 patients; corticosteroid therapy [odds ratio (OR) 6250, 95% confidence interval (CI) 1.383-28.571, p = 0.017), corticosteroid dose (OR 8.862 CI 2.299-70.258, p= 0.006), duration of mechanical ventilation (OR 1.199 CI) 1.088-1.322, p< 0.001). CONCLUSIONS: Secondary bacterial pneumonia was found to be associated with the severity and survival of the disease in patients admitted to ICU due to COVID-19. Duration of mechanical ventilation and use of corticosteroids and high-dose corticosteroids are risk factors for secondary bacterial pneumonia.

Clinical efficacy and safety of tigecycline based on therapeutic drug monitoring for carbapenem-resistant Gram-negative bacterium pneumonia in intensive care units.

BACKGROUND: We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. METHODS: This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline's clinical efficacy and safety were performed to control confounding factors. RESULTS: For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 µg/mL in the HD group, which was higher than in the SD group (0,21 µg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005-1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755-1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. CONCLUSIONS: Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient's age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.

Geriatric Pharmacotherapy Case Series: Chronic Obstructive Pulmonary Disease.

Patient is a 77-year-old female who is a retired teacher living with her husband. Patient presents to the clinic for a post-hospital discharge visit. She was treated for bacterial pneumonia with combination therapy of azithromycin and cefpodoxime. She was diagnosed with COPD seven years ago when she had to be treated for chronic dyspnea, cough, and sputum that kept her breathless and required hospitalization.