Prevention of ventilator-associated pneumonia with inhaled antibiotics

The direct delivery of inhaled antibiotics to the respiratory tract has been a subject of enduring interest among medical practitioners and researchers due to the associated favorable pharmacokinetics.This interest has been particularly pronounced in the context of critically illpatients,wherehealthcare-associatedpulmonary infections represent a significant challenge,driving continued exploration of inhaled antibiotics for intubated patients.Recent high-level evidence has shown a very promising application in the field of ventilator-associated pneumonia (VAP) prevention.^([1]).

Causative bacteria of ventilator-associated pneumonia in intensive care unit in Bahrain:Prevalence and antibiotics susceptibility pattern

BACKGROUND Ventilator-associated pneumonia(VAP)is defined as pneumonia that occurs two calendar days following endotracheal intubation or after that.It is the most common infection encountered among intubated patients.VAP incidence showed wide variability between countries.AIM To define the VAP incidence in the intensive care unit(ICU)in the central gove-rnment hospital in Bahrain and review the risk factors and the predominant bacterial pathogens with their antimicrobial susceptibility pattern.METHODS The research was a prospective cross-sectional observational study over six months from November 2019 to June 2020.It included adult and adolescent patients(>14 years old)admitted to the ICU and required intubation and mechanical ventilation.VAP was diagnosed when it occurred after 48 h after endotracheal intubation using the clinical pulmonary infection score,which considers the clinical,laboratory,microbiological,and radiographic evidence.RESULTS The total number of adult patients admitted to the ICU who required intubation and mechanical ventilation during the study period was 155.Forty-six patients developed VAP during their ICU stay(29.7%).The calculated VAP rate was 22.14 events per 1000 ventilator days during the study period,with a mean age of 52 years±20.Most VAP cases had late-onset VAP with a mean number of ICU days before the development of VAP of 9.96±6.55.Gram-negative contributed to most VAP cases in our unit,with multidrug-resistant Acinetobacter being the most identified pathogen.CONCLUSION The reported VAP rate in our ICU was relatively high compared to the international benchmark,which should trigger a vital action plan for reinforcing the implementation of the VAP prevention bundle.

Comparison of the Use of Conventional and Antibiotic-Coated Tracheal Tubes and EVAC on the Incidence of Ventilator-Associated Pneumonia (VAP)

Ventilator-associated pneumonia (VAP) is one of the most important hospital infections in hospitalized patients, which is associated with increased mortality and patient costs. The tracheal tube itself seems to be a major risk factor for VAP. Contaminated secretions pass through the endotracheal tube and reach the lungs. Also, bacteria form a bacterial biofilm on the tracheal tube and are transferred from there to the lungs. Different tracheal tube designs have been produced to overcome these cases. The purpose of this study is to investigate the effect of an Evac tracheal tube covered with antibiotics and normal on the incidence of pneumonia caused by the ventilator. Research method: 180 patients were randomly intubated in three groups of 60 people with three types of tracheal tubes, Evac and Bactiguard. Clinical examinations, endotracheal tube aspiration culture, and chest radiography were obtained from the patients and the incidence of VAP was calculated based on the CPIS standard. The relationship between the type of endotracheal tube and the incidence of VAP and the length of stay in the intensive care unit (ICU) and being discharged alive from the ICU were investigated. Findings and conclusions: The average incidence of VAP for the group of patients intubated with a conventional tracheal tube was 50%, EVAC was 45% and Bactiguard was 40%. The results showed that there is no significant relationship between the incidence of ventilator-induced pneumonia and the type of tracheal tube. The incidence of ventilator-induced pneumonia was not significantly reduced by suctioning subglottic secretions and Bactiguard tracheal tubes. It seems that using one method alone is not effective in reducing ventilator-induced pneumonia.

Risk factors for ventilator-associated pneumonia in trauma patients:A descriptive analysis

BACKGROUND:We sought to evaluate the risk factors for developing ventilator-associated pneumonia(VAP)and whether the location of intubation posed a risk in trauma patients.METHODS:Data were retrospectively reviewed for adult trauma patients requiring intubation for>48 hours,admitted between 2010 and 2013.Patients’demographics,clinical presentations and outcomes were compared according to intubation location(prehospital intubation[PHI]vs.trauma room[TRI])and presence vs.absence of VAP.Multivariate regression analysis was performed to identify predictors of VAP.RESULTS:Of 471 intubated patients,332 patients met the inclusion criteria(124 had PHI and208 had TRI)with a mean age of 30.7±14.8 years.PHI group had lower GCS(P=0.001),respiratory rate(P=0.001),and higher frequency of head(P=0.02)and chest injuries(P=0.04).The rate of VAP in PHI group was comparable to the TRI group(P=0.60).Patients who developed VAP were 6 years older,had significantly lower GCS and higher ISS,head AIS,and higher rates of polytrauma.The overall mortality was 7.5%,and was not associated with intubation location or pneumonia rates.In the early-VAP group,gram-positive pathogens were more common,while gram-negative microorganisms were more frequently encountered in the late VAP group.Logistic regression analysis and modeling showed that the impact of the location of intubation in predicting the risk of VAP appeared only when chest injury was included in the models.CONCLUSION:In trauma,the risk of developing VAP is multifactorial.However,the location of intubation and presence of chest injury could play an important role.

Effect of traditional Chinese preparation Xuebijing on inflammatory markers in patients with ventilator-associated pneumonia

Objective:To observe the effect of Xuebijing,a complex traditional Chinese preparation,on inflammation and prognosis of patients with pneumonia.Methods:The patients with ventilator-associated pneumonia in the intensive care unit(ICU)were randomly divided into the control group and the treatment group with 35 cases in each group.Both groups were given routine treatment such as anti-inflammatory drugs,rehydration,expectorant,and nutritional support,while the treatment group was additionally given Xuebijing injection.Serum C-reactive protein(CRP),clinical pulmonary infection score(CPIS),acute physiology,and chronic health scoreⅡ(APACHEⅡ)were recorded before treatment,the 3rd and 7th day after treatment.The duration of antibiotic use,mechanical ventilation,ICU stay,and mortality during 28 days was recorded.Results:There was no significant difference in CRP,CPIS,and APACHEⅡbetween the two groups before treatment(P>0.05).The improvement of CRP,CPIS,and APACHEⅡin the treatment group was better than those in the control group on the 3 and 7 days after treatment,and the differences were statistically significant(P<0.05).The duration of antibiotic use,mechanical ventilation,and ICU stay in the treatment group were less than those in the control group(P<0.05).The 28-day mortality of the treatment group was lower than that of the control group,but the difference was not statistically significant(P>0.05).Conclusions:Xuebijing injection can improve the inflammatory indexes of patients with ventilator-associated pneumonia,and can partly improve the prognosis.

Respiratory mechanics,ventilator-associated pneumonia and outcomes in intensive care unit

AIM To evaluate the predictive capability of respiratory mechanics for the development of ventilator-associated pneumonia (VAP) and mortality in the intensive care unit(ICU) of a hospital in southern Brazil. METHODS A cohort study was conducted between, involving a sample of 120 individuals. Static measurements of compliance and resistance of the respiratory system in pressure-controlled ventilation (PCV) and volumecontrolled ventilation(VCV) modes in the 1 st and 5 th days of hospitalization were performed to monitor respiratory mechanics. The severity of the patients' illness was quantified by the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ). The diagnosis of VAP was made based on clinical, radiological and laboratory parameters.RESULTS The significant associations found for the development of VAP were APACHE Ⅱ scores above the average(P = 0.016), duration of MV (P = 0.001) and ICU length of stay above the average(P = 0.003), male gender(P = 0.004), and worsening of respiratory resistance in PCV mode(P = 0.010). Age above the average(P < 0.001), low level of oxygenation on day 1(P = 0.003) and day 5 (P = 0.004) and low lung compliance during VCV on day 1 (P = 0.032) were associated with death as the outcome.CONCLUSION The worsening of airway resistance in PCV mode indicated the possibility of early diagnosis of VAP. Low lung compliance during VCV and low oxygenation index were death-related prognostic indicators.

Antimicrobial resistance pattern in ventilator-associated pneumonia in an intensive care unit of Babol, northern Iran

Objective:To investigate antibiotic resistance pattern of ventilator-assiated pneumonia (VAP) generating microorganisms,and quantitative culture and determining antibiotic sensitivity.Methods:This cross sectional study was performed on 50 patients suffering from VAP in intensive care unit of Ayatollah Rouhani Hospital,Babol,Iran during 2014-2015.VAP was probable for them based on clinical signs and the criteria of Clinical Pulmonary Infection Score standards.Lower respiratory samples were given under bronchoalveolar lavage and quantitative culture was done on them.Afterwards by microdilution method,minimal inhibitory concentration based on respective microorganisms,considering clinical pulmonary infection score were determined.Results:From 50 investigated samples in this study,the most common microorganisms were Acinetobacter baumannii (A.baumannii) (70%) then Pseudomonas aeruginosa (12%),Staphylococcus aureus (8%) and Klebsiella pneumonia (3%).In our study A.baummannii showed approximate 100% resistance to all antibiotics,in a way that A.baumannii resistance to imipenem and meropenem and piperacillin/tazobactam each was 97.1%.The most resistance of Pseudomonas aeruginosa was 66.7% to each cefepime and ceftazidime and clavulanate/ticarcillin.Staphylococcus aureus showed 75% resistance to nafcillin,cloxacillin and resistance in case of vancomycin was not seen.Conclusion:In current study,A.baumannii had the most prevalence among VAP and this species is resistant to most of antibiotics.Using ceftazidime,cefepime and clavulanate/ticarcillin,in treatment of the patients suffering VAP is not reasonable.

Ventilator-associated pneumonia in patients with cancer: Impact of multidrug resistant bacteria

BACKGROUND Patients with cancer have several risk factors for developing respiratory failure requiring mechanical ventilation(MV).The emergence of multidrug resistant bacteria(MDRB)has become a public health problem,creating a new burden on medical care in hospitals,particularly for patients admitted to the intensive care unit(ICU).AIM To describe risk factors for ventilator-acquired pneumonia(VAP)in patients with cancer and to evaluate the impact of MDRB.METHODS A retrospective study was performed from January 2016 to December 2018 at a cancer referral center in Mexico City,which included all patients who were admitted to the ICU and required MV≥48 h.They were classified as those who developed VAP versus those who did not;pathogens isolated,including MDRB.Clinical evolution at 60-d was assessed.Descriptive analysis was carried out;comparison was performed between VAP vs non-VAP and MDRB vs non-MDRB.RESULTS Two hundred sixty-three patients were included in the study;mean age was 51.9 years;52.1%were male;68.4%had solid tumors.There were 32 episodes of VAP with a rate of 12.2%;11.5 episodes/1000 ventilation-days.The most frequent bacteria isolated were the following:Klebsiella spp.[n=9,four were Extended-Spectrum Beta-Lactamase(ESBL)producers,one was Carbapenem-resistant(CR)];Escherichia coli(n=5,one was ESBL),and Pseudomonas aeruginosa(n=8,two were CR).One Methicillin-susceptible Staphylococcus aureus was identified.In multivariate analysis,the sole risk factor associated for VAP was length of ICU stay(OR=1.1;95%CI:1.03-1.17;P=0.003).Sixty-day mortality was 53%in VAP and 43%without VAP(P=0.342).There was not higher mortality in those patients with MDRB.CONCLUSION This study highlights the high percentage of Gram-negative bacteria,which allows the initiation of empiric antibiotic coverage for these pathogens.In this retrospective,single center,observational study,MDRB VAP was not directly linked to increased mortality at 60 days.

Linezolid versus Vancomycin for the Treatment of Methicillin-Resistant <i>Staphylococcus aureus</i>in Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia at Tertiary Care Hospital

Aim: To evaluate morbidity and mortality rate, clinical cure rate and cost of linezolid versus vancomycin in patients who have hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) or Healthcare-associated pneumonia (HCAP) caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Retrospective analysis data. Data were collected for adult patients admitted to King Faisal Specialist Hospital and Research Centre-Jeddah (KFSH & RC-J) from January 2010 to May 2015. Method: A total of 88 patients with HAP, VAP and HCAP caused by MRSA treated with vancomycin (IV) or linezolid (IV or PO) either as empirically or directed therapy ≥ 7 days. They are retrospectively evaluated and analyzed. The primary end points are morbidity and mortality rate as well as clinical cure rate. The secondary end point is the cost analysis for each medication. Results: A total of 40 patients (ICU, n = 13 (32.5% and non ICU, n = 27 (67.5%)) were included in the study. Among vancomycin, n = 21 (52.5%);age (54.95 ± 18.255) and linezolid, n = 19 (74.5%);age (48.684 ± 25.593), there was no statistical differences in mortality and morbidity rate (P = 0.375). Clinical cure rate (fever improvement, 12 (57.1%) vs 12 (63.2%);P = 0.698, leukocytosis improvement, 15 (71.4%) vs 14 (73.7%);P = 0.873, purulent sputum improvement, 6 (28.6%) vs 4 (21.1%);P = 0.429, dyspnea improvement, 8 (38.1%) vs 3 (15.8%);P = 0.115,cough improvement 4 (19.0%) vs 4 (21.1%);P = 0.592, microbiological eradication of MRSA from sputum culture, 2 (9.5%) vs 6 (31.6%);P = 0.089 and improvement of radiographic finding (pulmonary infiltration), 17 (81.0%) vs 16 (84.2%);P = 0.559) of vancomycin vs linezolid, respectively. The cost analysis in the treatment of MRSA pneumonia with linezolid is statistical significantly higher than vancomycin. The mean cost of vancomycin = 185.9143 SR and of linezolid = 4547.3684 SR (P Conclusion: There are no statistical differences in mortality and morbidity rate and clinical cure rate between linezolid and vancomycin in the treatment of MRSA in HAP, VAP, and HCAP. However, the cost of linezlid is significantly higher than vancomycin during the treatment period of one patient.

Klebsiella pneumoniae infections after liver transplantation:Drug resistance and distribution of pathogens,risk factors,and influence on outcomes

BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.

Clinical characteristics of community-acquired pneumonia in children caused by mycoplasma pneumoniae with or without myocardial damage:A single-center retrospective study

BACKGROUND Mycoplasma pneumoniae(MP)is a prevalent pathogen that causes respiratory infections in children and adolescents.AIM To assess the differences in the clinical features of MP-associated communityacquired pneumonia(CAP)in children who presented with mild or severe mycoplasma pneumoniae pneumonia(MPP);to identify the incidence of myocardial damage between the two groups.METHODS This work is a retrospective study.We identified children between 2 mo and 16 years of age with clinical and radiological findings consistent with CAP.We admitted patients to the inpatient department of the Second Hospital of Jilin University,Changchun,China,from January 2019 to December 2019.RESULTS A total of 409 hospitalized patients were diagnosed with MPP.Among them were 214(52.3%)males and 195(47.7%)females.The duration of fever and cough was the longest in severe MPP cases.Similarly,plasma levels of highly sensitive Creactive protein(t=-2.834,P<0.05),alanine transaminase(t=-2.511,P<0.05),aspartate aminotransferase(t=-2.939,P<0.05),and lactate dehydrogenase(LDH)(t=-2.939,P<0.05)were all elevated in severe MPP cases compared with mild MPP cases,and these elevations were statistically significant(P<0.05).Conversely,the neutrophil percentage was significantly lower in severe MPP cases than in mild MPP cases.The incidence of myocardial damage was significantly higher in severe MPP cases than in mild MPP cases(χ^(2)=157.078,P<0.05).CONCLUSION Mycoplasma pneumoniae is the main cause of CAP.The incidence of myocardial damage was higher and statistically significant in severe MPP cases than in mild MPP cases.

Chinese herbal medicine combined with Western medicine for Mycoplasma pneumoniae pneumonia in children:An overview of systematic reviews

Objective:To summarize the characteristics and evaluate the quality of the methodology and evidence within systematic reviews(SRs)of Chinese herbal medicine(CHM)for Mycoplasma pneumoniae pneumonia(MPP)inchildren.Methods:SRs of randomized controlled trials were searched using PubMed,the Cochrane Library,Embase,the Chinese National Knowledge Infrastructure Databases(CNKI),the Chinese Scientific Journals Database(VIP),Wanfang,and the SinoMed Database.SRs on the use of CHM alone or in combination with Western medications for MPP in children were included.The study compared the effects of Western medicine alone with those of CHM.The evidence quality using the A Measurement Tool to Assess Systematic Reviews(AMSTAR)2,the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)2020,and the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)criteria.The primary indicators were the total effective rate,fever subsidence time,and cough disappearance time.The secondary outcomes were pulmonary rale disappearance time,average hospitalization time,lung X-ray infiltrate disappearance time,immunological indices,and inflammatory cytokine levels.Results:Twelve relevant SRs were included;75%(9/12)were assessed as very low quality,and 25%(3/12)Were rated as low quality using the AMSTAR 2 criteria.According to the PRISMA 2020 checklist,the average SR score was 20.3 out of a 27 point maximum.In all SRs,CHM demonstrated improvement in symptoms and signs among children with MPP.The evidence quality using the GRADE criteria ranged from"very low"(>50%)to"moderate"(<5%).The most common downgrading factor was imprecision,followed by publication bias and inconsistency.Conclusion:This overview highlights the limited quality of the methodology and evidence of the included SRs.Although the included studies showed the beneficial effects of CHM on MPP in children,it was difficult to draw firm conclusions owing to methodological flaws.

Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

A Hybrid Classification and Identification of Pneumonia Using African Buffalo Optimization and CNN from Chest X-Ray Images

An illness known as pneumonia causes inflammation in the lungs.Since there is so much information available fromvarious X-ray images,diagnosing pneumonia has typically proven challenging.To improve image quality and speed up the diagnosis of pneumonia,numerous approaches have been devised.To date,several methods have been employed to identify pneumonia.The Convolutional Neural Network(CNN)has achieved outstanding success in identifying and diagnosing diseases in the fields of medicine and radiology.However,these methods are complex,inefficient,and imprecise to analyze a big number of datasets.In this paper,a new hybrid method for the automatic classification and identification of Pneumonia from chest X-ray images is proposed.The proposed method(ABOCNN)utilized theAfrican BuffaloOptimization(ABO)algorithmto enhanceCNNperformance and accuracy.The Weinmed filter is employed for pre-processing to eliminate unwanted noises from chest X-ray images,followed by feature extraction using the Grey Level Co-Occurrence Matrix(GLCM)approach.Relevant features are then selected from the dataset using the ABO algorithm,and ultimately,high-performance deep learning using the CNN approach is introduced for the classification and identification of Pneumonia.Experimental results on various datasets showed that,when contrasted to other approaches,the ABO-CNN outperforms them all for the classification tasks.The proposed method exhibits superior values like 96.95%,88%,86%,and 86%for accuracy,precision,recall,and F1-score,respectively.

Occurrence of K1 and K2 serotypes and genotypic characteristics of extended spectrumβ-lactamases-producing Klebsiella pneumoniae isolated from selected hospitals in Malaysia

Objective:To determine the distribution,phenotypic and genetic background of extended spectrumβ-lactamases(ESBL)-producing Klebsiella(K.)pneumoniae clinical isolates associated with K1 and K2 serotypes in two selected hospitals in Malaysia.Methods:A total of 192 K.pneumoniae isolates were collected and subjected to antibiotic susceptibility,hypermucoviscosity test and multiplex PCR to detect the presence of K1-and K2-serotype associated genes.Multilocus sequence typing(MLST)was performed on ESBL-producing K.pneumoniae isolates presented with K1 and K2 serotypes,followed by phylogenetic analysis.Results:A total of 87 out of 192(45.3%)of the K.pneumoniae isolates collected were ESBL producers.However,only 8.3%(16/192)and 10.9%(21/192)of the total isolates were detected to carry K1-and K2-serotype associated genes,respectively.Statistical analysis showed that K1 and K2 capsular serotypes were not significantly associated with ESBL phenotype(P=0.196).However,they were significantly associated with hypervirulent,as demonstrated by the positive string test(P<0.001).MLST analysis revealed that ST23 as the predominant sequence type(ST)in the K1 serotype,while the ST in the K2 serotype is more diverse.Conclusions:Although the occurrence of ESBL-producing isolates among the hypervirulent strains was low,their coexistence warrants the need for continuous surveillance.MLST showed that these isolates were genetically heterogeneous.

Protective eff ect and mechanism of nanoantimicrobial peptide ND-C14 against Streptococcus pneumoniae infection

BACKGROUND:Streptococcus pneumoniae(S.pneumoniae)is a common pathogen that causes bacterial pneumonia.However,with increasing bacterial resistance,there is an urgent need to develop new drugs to treat S.pneumoniae infections.Nanodefensin with a 14-carbon saturated fatty acid(ND-C14)is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of humanα-defensin 5(HD5)via an amide bond.However,it is unclear whether ND-C14 is effective against lung infections caused by S.pneumoniae.METHODS:In vitro,three groups were established,including the control group,and the HD5 and ND-C14 treatment groups.A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S.pneumoniae.The morphological changes of S.pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy.In vivo,mice were divided into sham,vehicle,and ND-C14 treatment groups.Mice in the sham group were treated with 25μL of phosphate-buffered saline(PBS).Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25μL of bacterial suspension with 2×108 CFU/mL(total bacterial count:5×10^(6) CFU),and then the mice were given 25μL PBS or intratracheally injected with 25μL of ND-C14(including 20μg or 50μg),respectively.Survival rates were evaluated in the vehicle and ND-C14 treatment groups.Bacterial burden in the blood and bronchoalveolar lavage fluid were counted.The lung histology of the mice was assessed.A propidium iodide uptake assay was used to clarify the destructive eff ect of ND-C14 against S.pneumoniae.RESULTS:Compared with HD5,ND-C14 had a better bactericidal eff ect against S.pneumoniae because of its stronger ability to destroy the membrane structure of S.pneumoniae in vitro.In vivo,ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S.pneumoniae.ND-C14 reduced bacterial burden and lung tissue injury.Moreover,ND-C14 had a membrane permeation eff ect on S.pneumoniae,and its destructive ability increased with increasing ND-C14 concentration.CONCLUSION:The ND-C14 may improve bactericidal eff ects on S.pneumoniae both in vitro and in vivo.

iTRAQ-based proteomics reveals the mechanism of action of Yinlai decoction in treating pneumonia in mice consuming a high-calorie diet

Objective:To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie dietinduced pneumonia through proteomics analysis.Methods:Based on the Gene Expression Omnibus(GEO)database,lung tissue samples from normal and high-fat diet(HFD)fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses.In the animal experiments,mice were randomly divided into the control(N),high-calorie diet pneumonia(M),and Yinlai decoction treatment(Y)groups.Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d.The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d.Pathological evaluation of the lung tissue was performed.Differentially expressed proteins(DEPs)in the lung tissue were identified using quantitative proteomics and bioinformatics analyses.The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory(MGL)Tools.DEPs were verified by western blot.Results:GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue.The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet.A total of 47 DEPs were identified between the Y and M groups.Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle(TCA)and oxidative phosphorylation.The protein-protein interaction network revealed that Atp5a1,Pdha1,and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction.Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide,praeruptorin B,chrysoeriol,and other components in Yinlai decoction to Atp5a1.Conclusion:The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation.Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.

Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation

BACKGROUND The number of patients undergoing solid organ transplantation has increased annually.However,infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants.Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4’’-O-isovaleryltransferase gene(ist)from streptomyces thermotoleran.Carrimycin has good antibacterial and antiviral effects.However,no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia(SP)after solid organ transplantation.AIM To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment.METHODS In March 2022,ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022.When the condition was critical and difficult to control with other drugs,carrimycin was administered.These ten patients'clinical features and treatment protocols were retrospectively analyzed,and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated.RESULTS All ten patients were included in the analysis.Regarding etiological agent detection,there were three cases of fungal pneumonia,two cases of bacterial pneumonia,two cases of Pneumocystis pneumonia,and three cases of mixed infections.After treatment with carrimycin,the disease in seven patients significantly improved,the course of the disease was significantly shortened,fever was quickly controlled,chest computed tomography was significantly improved,and oxygenation was significantly improved.Finally,the patients were discharged after curing.One patient died of acute respiratory distress syndrome,and two patients discontinued treatment.CONCLUSION Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation.Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.

Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria

BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.