Objective To analyze the relationship between clinical drug utilization and the risk of nosocomial infections among hospitalized patients,and provide evidence for the prevention and control of nosocomial infections.Methods This study adopted a retrospective case-control design.The case group included 209 patients with nosocomial infection reported from January 2023 to December 2023 in a tertiary hospital.The control group included 209 patients without nosocomial infection during the same period.The patients in the control group were selected by stratified sampling based on Charlson Comorbidity Index(CCI).Results Univariate analysis showed that proton pump inhibitors,antacids,immunosuppressants and prior antimicrobial combination therapy increased the risk of nosocomial infection(P＜0.05).Multivariate log-binomial regression analysis showed that proton pump inhibitors,immunosuppressive drugs,and prior antimicrobial combination therapy were correlated with nosocomial infection.The corresponding relative risk(RR)was 1.31(95％CI:1.07-1.60),1.40(95％CI:1.02-1.91),and 1.66(95％CI:1.01-2.74),respectively.Further analysis indicated that the patients with nosocomial infection had longer time in use of proton pump inhibitors and prior antimicrobial combination therapy than the patients in the control group(Z=-6.331,P＜0.001;Z=-2.667,P=0.008).The trend Chi-square test showed that there was a dose-response relationship for proton pump inhibitors(x2=73.869,P＜0.001),immunosuppressive drugs(x2=16.530,P＜0.001),and prior antimicrobial combination therapy(x2=35.107,P＜0.001).Conclusions The use of immunosuppressants,proton pump inhibitors and antimicrobial combination therapy increases the risk of nosocomial infections in hospitalized patients.The prolonged use of these drugs will further increase the risk of nosocomial infection.

Objective To develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

Objective To investigate the efficacy of voriconazole in the treatment of pulmonary tuberculosis complicated with chronic pulmonary aspergillosis(CPA)based on CYP2C19 gene polymorphism detection and examine the factors affecting the efficacy for improving targeted therapy in clinical practice.Methods A total of 207 patients with pulmonary tuberculosis complicated with CPA treated in the Third People's Hospital of Kunming from December 2018 to November 2022 were randomly assigned to an observation group(105 cases)or a control group(102 cases).The patients in the control group received standard voriconazole treatment,while the patients in the observation group had their voriconazole regimen tailored based on CYP2C19 genotyping results.Plasma drug concentration levels,efficacy,and safety were compared between the two groups and in terms of CYP2C19 genotypes.Logistic regression analysis was used to identify the factors affecting treatment efficacy.Results The observation group showed significantly higher plasma voriconazole concentrations and overall antifungal efficacy compared to the control group(P＜0.05).In the observation group,CYP2C19 genotyping identified 37 extensive metabolizers(EM),47 intermediate metabolizers(IM),and 21 poor metabolizers(PM).Plasma concentration of voriconazole did not show significant difference between EM and IM(P＞0.05),but both PM and IM were associated with significantly lower plasma concentration of voriconazole than PM(P＜0.05).The clinical efficacy rate was 100％for PM,91.5％for IM,and 83.8％for EM(P＜0.05).The incidence of adverse events did not show significant difference among the three genotypes(P＞0.05).Logistic regression analysis revealed that lung cavitation,hypoalbuminemia,and agranulosis were significantly correlated with therapeutic efficacy(P＜0.05).Conclusions CYP2C19 gene polymorphism detection is valuable in clinical practice.It can inform anti-aspergillus therapy with voriconazole to effectively improve symptoms and clinical efficacy in patients with pulmonary tuberculosis complicated with CPA.Meanwhile,clinicians should be aware of the factors such as hypoproteinemia,agranulocytosis,and lung cavitation that may affect the efficacy of voriconazole.

Objective This study aimed to evaluate the interaction between antiretroviral drug efavirenz and anti-tuberculosis 1H3P3(isoniazid plus rifapentine)in people living with HIV.Methods HIV-positive individuals on efavirenz-containing(600 mg)antiretroviral therapy(ART)received 1H3P3 regimen containing rifapentine(450 mg)plus isoniazid(400 mg)3 times a week for 1 month.Efavirenz concentrations were measured at weeks 0,2,4,8.Rifapentine concentration was determined at weeks 2 and 4.HIV RNA load was determined at weeks 0 and 8.Treatment target was efavirenz concentration＞1 mg/L.The anti-TB prevention was considered acceptable if the target of efavirenz concentration was achieved in more than 80％of participants.The participants were followed up for 18 months to evaluate the efficacy of treatment.Results Thirty-one participants living with HIV were enrolled in the study.Two participants were excluded from PK analysis because his/her baseline efavirenz concentration＜1 mg/L,suggesting poor treatment adherence.Evaluable PK data were available for 29 participants,including 23(79.3％)males.The median[interquartile range(IQR)]age of the participants was 43.0(32.5,53.5)years.The median(IQR)efavirenz plasma concentration was 2.33(1.96,2.34)mg/L at week 0,2.32(1.90,3.28)mg/L at week 2,2.07(1.83,3.09)mg/L at week 4,and 2.71(2.14,3.33)mg/L at week 8.Efavirenz concentration did not show significant difference between the 4 time points(P＞0.05).Median(IQR)rifapentine concentration was 9.36(6.23,16.47)mg/L at week 2,and 9.36(6.41,15.56)mg/L at week 4.Rifapentine concentration did not show significant difference between week 2 and week 4(P＞0.05).Efavirenz concentrations was＞1 mg/L in all participants at weeks 2,4,and 8.Furthermore,efavirenz concentration was significantly higher in females and patients with body weight＜60 kg compared with males and those with body weight ≥60 kg(P＜0.05).None of the participants had symptoms or signs of active tuberculosis during 18-month follow-up.Conclusions Isoniazid plus rifapentine(1H3P3 regimen)did not have significant effect on the plasma concentrations of efavirenz.

Objective To investigate the changing prevalence and antimicrobial resistance profiles of carbapenem-resistant Enterobacterales(CRE)in Xinjiang Uygur Autonomous Region from 2017 to 2021.Methods Relevant CRE data in hospitals across Xinjiang from 2017 to 2021 were summarized according to the unified protocol of the National Antimicrobial Resistance Surveillance Network.The data were statistically analyzed by WHONET 5.6 software.Results A total of 5 071 CRE strains were identified from 165 786 strains of Enterobacterales in Xinjiang in the five-year period.The prevalence of CRE was 2.8％in 2017,3.2％in 2018,2.9％in 2019,3.1％in 2020,and 3.2％in 2021.The highest prevalence(3.3％)was in northern Xinjiang and the lowest prevalence(0)was in eastern Xinjiang.The prevalence of CRE in tertiary hospitals was higher than that in secondary hospitals.The top three species among the 5 071 CRE strains were carbapenem-resistant Klebsiella pneumoniae,carbapenem-resistant Escherichia coli,and carbapenem-resistant Enterobacter cloacae.The CRE strains were mainly isolated from the patients in ICU(34.6％),respiratory ICU(8.1％),neurosurgery(7.5％),and respiratory medicine(5.2％).The distribution of CRE species varied with patient age and gender.The carbapenem-susceptible Enterobacterales and CRE strains isolated from children were less resistant to the commonly used antibiotics in clinical practice than the corresponding strains isolated from adult patients.Conclusions The prevalent CRE strains from patients in Xinjiang are still serious.It is necessary to strengthen the surveillance of bacterial resistance and carry out multidisciplinary linkage to curb the spread and outbreak of CRE.

Objective To investigate the value of neutrophil to lymphocyte ratio(NLR)and lymphocyte to monocyte ratio(LMR)in the diagnosis and prognosis of patients with sepsis.Methods From January 2022 to December 2022,patients in the First Affiliated Hospital of Soochow University were recruited in this study,including 47 patients with sepsis(sepsis group),31 with infection but not diagnosed as sepsis(infection group),and 25 healthy individuals(control group)were simultaneously chosen.Patients with sepsis were assigned to non-shock group(32 cases)or shock group(15 cases),survivors group(38 cases)or deaths group(9 cases).Procalcitonin(PCT),C-reactive protein(CRP)and routine blood tests were analyzed and compared between groups.Spearman's correlation test was used to analyze the correlation among NLR,LMR and PCT,PCR,lymphocyte,monocyte,neutrophil,platelet and SOFA scores,the diagnostic value of NLR and LMR in sepsis was evaluated by plotting the receiver operating characteristic(ROC)curve.Results The NLR was 12.54(7.53,23.42)in sepsis group,3.85(1.83,5.64)in infection group,and 1.71(1.39,2.20)in normal control group.The corresponding LMR was 1.58(1.07,3.03),2.81(1.53,4.76),and 5.16(4.04,6.59),respectively.NLR was negatively correlated with LMR(rs=-0.469,P＜0.05).The NLR on day 7(NLR7)was 6.56(3.90,10.72)in the non-shock group and 15.20(7.53,27.31)in shock group.The corresponding △NLR7 was-1.64(-5.75,0.41)and 1.98(-0.48,13.79)in the two groups.The shock group had significantly higher △NLR7 than the non-shock group(P＜0.05).NLR7 was 7.10(4.09,12.96)in the survivors and 15.20(10.45,32.82)in the deaths group.The corresponding △NLR7 was-0.65(-5.58,1.58)and 5.02(-1.12,17.06)in the two groups.The deaths group had significantly higher △NLR7 than the survivors group(P＜0.05).The LMR on day 7(LMR7)was 2.22(1.64,3.78)in the non-shock group and 1.29(0.66,2.03)in shock group.The corresponding △LMR7 was 0.38(-0.37,1.17)and-0.19(-0.78,0.25)in the two groups.The shock group had significantly lower △LMR7 than the non-shock group(P＜0.05).LMR7 was 2.12(1.49,3.42)in the survivors group and 1.09(0.53,1.78)in the deaths group.The deaths group had significantly lower LMR7 than the survivors group(P＜0.05).The AUC of NLR was 0.959 1(95％CI:0.910 5-1.000 0)in diagnosis of sepsis.The best cut-off value was 4.16.The A UC of LMR was 0.913 6(95％CI:0.846 4-0.980 8)in diagnosis of sepsis.The best cut-off value was 3.21.Conclusions NLR and LMR can be used to evaluate the severity and prognosis of patients with sepsis.These two markers may play a role in the diagnosis of sepsis.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To investigate the correlation between baseline plasma soluble triggering receptor expressed on myeloid cell-1(sTREM-1),steroid hormone cortisol and dehydroepiandrosterone(DHEA),immunoendocrine markers,and disease severity in patients with pulmonary tuberculosis(PTB).Methods From March 2020 to May 2022,76 PTB patients and 78 healthy controls were recruited.The plasma sTREM-1 levels were compared between controls and PTB patients.Plasma sTREM-1 and C-reactive protein(CRP),interleukin(IL)-6 and interferon(IFN)-y,erythrocyte sedimentation rate(ESR),steroid hormone cortisol and dehydroepiandrosterone(DHEA)were analyzed to correlate with inflammatory transcripts(IL-6,IFN-γ)in peripheral blood mononuclear cells.Results The sTREM,CRP,ESR,IL-6,IFN-γ,cortisol and cortisol/DHEA were significantly increased(P＜0.05)while DHEA was significantly decreased(P＜0.05)in PTB patients compared with the control group.Futhermore,severe PTB patients had higher sTREM-1 and ESR levels than mild and moderate PTB patients.Spearman correlation analysis showed that sTREM-1 was significantly positively correlated with CRP in all patients(P＜0.05).Only in patients with severe PTB,sTREM-1 was significantly positively correlated with cortisol/DHEA(P＜0.05),and significantly negatively correlated with DHEA(P＜0.05).Conclusions High plasma sTREM-1 levels may be an important factor contributing to the persistence of immunoendocrine imbalance specific to advanced disease in patients with PTB.

Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Objective To examine the diagnosis and treatment of disseminated infection caused by Enterocytozoon bieneusi in a child with leukemia and improve the awareness of the pathogen in clinical and laboratory practice.Methods A case of disseminated infection caused by Enterocytozoon bieneusi in a child with leukemia in Shanghai Children's Hospital was retrospectively analyzed,including diagnosis and treatment details.Similar cases were identified from PubMed,Wanfang Data,VIP,and CNKI databases since database establishment until June 30,2024,using search terms"Enterocytozoon bieneusi".The relevant literature was reviewed.Results This child had acute lymphoblastic leukemia as the underlying disease and was admitted to hospital for antimicrobial treatment due to fever and abdominal discomfort.The case was considered bacterial infection complicated with Enterocytozoon bieneusi infection,confirmed by detection of Klebsiella pneumoniae in blood and detection of Enterocytozoon bieneusi in blood and ascites by metagenomic next-generation sequencing(mNGS).The treatment was switched to tigecycline plus trimethoprim-sulfamethoxazole at a sufficient dose,which resulted in resolution of symptoms.Six months later,the patient suffered from acute lymphoblastic leukemia and bone marrow depression,Enterocytozoon bieneusi disseminated infection,septic shock.Her family gave up treatment and the child died.Literature review indicated that most patients infected with Enterocytozoon bieneusi had underlying conditions such as organ transplantation,AIDS,and leukemia associated with poor immunity.The onset symptoms are diarrhea,abdominal discomfort,and fever.Enterocytozoon bieneusi was detected by using methods such as modified Masson's trichrome stain,fluorescent calcofluor white staining,molecular detection techniques,and immunofluorescence.The patients were treated with drugs such as albendazole,nitazoxanide,fumagillin,and trimethoprim-sulfamethoxazole.Conclusions Enterocytozoon bieneusi is an opportunistic pathogenic fungus that infects immunocompromised patients and can cause abdominal discomfort,diarrhea,fever,and even disseminated infection and death.Conventional laboratory methods cannot culture Enterocytozoon bieneusi.Molecular detection techniques can be used to identify the pathogen early.