Antibiotic-induced microbiome depletion promotes intestinal colonization by Campylobacter jejuni in mice.

BACKGROUND: To establish a method to induce Campylobacter jejuni colonization in the intestines of C57BL/6 mice through antibiotic-induced microbiome depletion. RESULTS: Fifty-four female C57BL/6 mice were divided into the normal, control, and experimental groups. The experimental group was administered intragastric cefoperazone sodium and sulbactam sodium (50 mg/mL) for 2 days; then, the experimental and control mice were intragastrically administered 200 µL C. jejuni, which was repeated once more after 2 days. Animal feces were collected, and the HipO gene of C. jejuni was detected using TaqMan qPCR from day 1 to day 14 after modeling completion. Immunofluorescence was used to detect intestinal C. jejuni colonization on day 14, and pathological changes were observed using hematoxylin and eosin staining. Additionally, 16S rDNA analyses of the intestinal contents were conducted on day 14. In the experimental group, C. jejuni was detected in the feces from days 1 to 14 on TaqMan qPCR, and immunofluorescence-labeled C. jejuni were visibly discernable in the intestinal lumen. The intestinal mucosa was generally intact and showed no significant inflammatory-cell infiltration. Diversity analysis of the colonic microbiota showed significant inter-group differences. In the experimental group, the composition of the colonic microbiota differed from that in the other 2 groups at the phylum level, and was characterized by a higher proportion of Bacteroidetes and a lower proportion of Firmicutes. CONCLUSIONS: Microbiome depletion induced by cefoperazone sodium and sulbactam sodium could promote long-term colonization of C. jejuni in the intestines of mice.

Halloysite nanotubes-based hybrid silica monolithic spin tip for hydrophilic solid-phase extraction of sulbactam, cefoperazone, and cefuroxime in whole blood.

In this study, we proposed a novel method utilizing polyethyleneimine (PEI)-modified halloysite nanotubes (HNTs)-based hybrid silica monolithic spin tip to analyze hydrophilic ß-lactam antibiotics and ß-lactamases inhibitors in whole blood samples for the first time. HNTs were incorporated directly into the hybrid silica monolith via a sol-gel method, which improved the hydrophilicity of the matrix. The as-prepared monolith was further modified with PEI by glutaraldehyde coupling reaction. It was found that the PEI-modified HNTs-based hybrid silica monolith enabled a large adsorption capacity of cefoperazone at 35.7 mg g-1. The monolithic spin tip-based purification method greatly reduced the matrix effect of whole blood samples and had a detection limit as low as 0.1 - 0.2 ng mL-1. In addition, the spiked recoveries of sulbactam, cefuroxime, and cefoperazone in blank whole blood were in the range of 89.3-105.4 % for intra-day and 90.6-103.5 % for inter-day, with low relative standard deviations of 1.3-7.2 % and 4.9-10.5 %, respectively. This study introduces a new strategy for preparing nanoparticles incorporated in a hybrid silica monolith with a high adsorption capacity. Moreover, it offers a valuable tool to monitor sulbactam, cefoperazone, and cefuroxime in whole blood from pregnant women with the final aim of guiding their administration.

Immune response to colonization of Candida albicans in mice treated with Cefoperazone.

Candida species are a normal human flora in humans' digestive and reproductive systems, oral cavity, skin, and mucosal surfaces. This study aimed to detect the immunological role of Candida infection by using some immunological markers. The results of levels in serum showed high concentrations of IgA (56.20 ± 12 pg/ml,29.55 ± 4.5 pg/ml respectively) and IgG (12.05 ± 3.218 pg/ml, 3.836 ± 1.23 pg/ml respectively) in mice infected with C. albicans and mice treated with Cefoperazone and infected with Candida with significant differences (P value < 0.05). The results showed high serum levels of IL-17(191.5 ± 42.81 pg/ml) and TLR2(7.651 ± 1.5 pg/ml) in group mice infected with C. albicans compared with negative control and group mice treated with Cefoperazone. Also, high levels of IL-17 (91.33 ± 4.816 pg/ml) and TLR2 (2.630 ± 0.5 pg/ml) in group mice treated with Cefoperazone and infected with Candida compared with negative control and group mice treated with Cefoperazone (P value < 0.05). The results of antibodies and immunological markers in the intestine showed high levels of IgA and IgG in mice infected with C.albicans (55.7 ± 4.9 pg/ml, 18.19 ± 0.63 pg/ml respectively).Also,IgA and IgG in mice treated with Cefoperazone and infected with Candida were high level (43.04 ± 2.1 pg/ml, 2.927 ± 0.2 pg/ml respectively) in mice infected with C. albicans with significant differences (P value < 0.05). The results levels of IL-17 and TLR2 were increased in mice infected with C. albicans (191.5 ± 42.81 pg/ml, 7.651 ± 1.5 pg/ml respectively) and mice treated with Cefoperazone and infected with Candida (91.33 ± 4.816 pg/ml,2.630 ± 0.5 pg/ml respectively) with significant differences (P < 0.05). In conclusion, this study demonstrated that cefoperazone treatment and infection by Candida albicans changed the microbiome components in the gut and finally can change host immune responses. It was observed that elevated levels of the antibodies production (IgA and IgG) and immunological markers (IL-17, and TLR2) in serum and the gut.

Montelukast and cefoperazone act as antiquorum sensing and antibiofilm agents against Pseudomonas aeruginosa.

AIMS: Drug repurposing is an attractive strategy to control biofilm-related infectious diseases. In this study, two drugs (montelukast and cefoperazone) with well-established therapeutic applications were tested on Pseudomonas aeruginosa quorum sensing (QS) inhibition and biofilm control. METHODS AND RESULTS: The activity of montelukast and cefoperazone was evaluated for Pqs signal inhibition, pyocyanin synthesis, and prevention and eradication of Ps. aeruginosa biofilms. Cefoperazone inhibited the Pqs system by hindering the production of the autoinducer molecules 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (the Pseudomonas quinolone signal or PQS), corroborating in silico results. Pseudomonas aeruginosa pyocyanin production was reduced by 50%. The combination of the antibiotics cefoperazone and ciprofloxacin was synergistic for Ps. aeruginosa biofilm control. On the other hand, montelukast had no relevant effects on the inhibition of the Pqs system and against Ps. aeruginosa biofilm. CONCLUSION: This study provides for the first time strong evidence that cefoperazone interacts with the Pqs system, hindering the formation of the autoinducer molecules HHQ and PQS, reducing Ps. aeruginosa pathogenicity and virulence. Cefoperazone demonstrated a potential to be used in combination with less effective antibiotics (e.g. ciprofloxacin) to potentiate the biofilm control action.

Ureidopenicillins Are Potent Inhibitors of Penicillin-Binding Protein 2 from Multidrug-Resistant Neisseria gonorrhoeae H041.

Effective treatment of gonorrhea is threatened by the increasing prevalence of Neisseria gonorrhoeae strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we demonstrated the promise of the third-generation cephalosporin cefoperazone as an antigonococcal agent due to its rapid second-order rate of acylation against penicillin-binding protein 2 (PBP2) from the ESC-resistant strain H041 and robust antimicrobial activity against H041. Noting the presence of a ureido moiety in cefoperazone, we evaluated a subset of structurally similar ureido ß-lactams, including piperacillin, azlocillin, and mezlocillin, for activity against PBP2 from H041 using biochemical and structural analyses. We found that the ureidopenicillin piperacillin has a second-order rate of acylation against PBP2 that is 12-fold higher than cefoperazone and 85-fold higher than ceftriaxone and a lower MIC against H041 than ceftriaxone. Surprisingly, the affinity of ureidopenicillins for PBP2 is minimal, indicating that their inhibitory potency is due to a higher rate of the acylation step of the reaction compared to cephalosporins. Enhanced acylation results from the combination of a penam scaffold with a 2,3-dioxopiperazine-containing R1 group. Crystal structures show that the ureido ß-lactams overcome the effects of resistance mutations present in PBP2 from H041 by eliciting conformational changes that are hindered when PBP2 interacts with the weaker inhibitor ceftriaxone. Overall, our results support the potential of piperacillin as a treatment for gonorrhea and provide a framework for the future design of ß-lactams with improved activity against ESC-resistant N. gonorrhoeae.

Nomogram Based on Clinical Characteristics to Predict 28-Day Mortality Among Patients with CRAB-BSI.

BACKGROUND: The drug resistance of carbapenem-resistant Acinetobacter baumannii bloodstream infections (CRAB-BSI), especially hospital-acquired infections, has promoted their rapid and vast spread. It is necessary to use reliable methods to establish better prediction models. According to Cox proportional hazards regression, a nomogram was established. METHODS: A retrospective cohort study among patients who were diagnosed with CRAB-BSI was performed from January 2020 to December 2022. Univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors regarding CRAB-BSI. Then, nomograms were used to calculate the area under the curve (AUC), C-index, and calibration curve to determine the predictive accuracy and dis-criminability. Decision curve analysis (DCA) was employed to further confirm the clinical effectiveness of the nomogram. RESULTS: A total of 98 cases were included in the comparison between the 28-day mortality group consisting of 32 patients and the 28-day survival group with 66 patients. The use of cefoperazone-sulbactam was significantly higher among patients who survived than among those who died. Univariable analysis revealed that factors such as primary diagnosis, time to inadequate antimicrobial therapy, and high serum creatinine and procalcitonin (PCT) levels were more prevalent in the mortality group. However, only primary diagnosis, time to inadequate antimicrobial therapy, and high PCT levels emerged as statistically significant risk factors for death in multivariate analysis and were used to construct the nomogram. The nomogram validation exhibited excellent performance. CONCLUSIONS: The nomogram was sufficiently accurate to predict the risk and prognostic factors of CRAB-BSI, allowing for individualized clinical decisions for future clinical work. The cefoperazone-sulbactam did have an effect, but more studies are needed to interpret it.

Spectrum and antibiotic sensitivity of bacterial keratitis: a retrospective analysis of eight years in a Tertiary Referral Hospital in Southwest China.

Purpose: The objective of this study was to investigate the epidemiological characteristics, distribution of isolates, prevailing patterns, and antibiotic susceptibility of bacterial keratitis (BK) in a Tertiary Referral Hospital located in Southwest China. Methods: A retrospective analysis was conducted on 660 cases of bacterial keratitis occurring between January 2015 and December 2022. The demographic data, predisposing factors, microbial findings, and antibiotic sensitivity profiles were examined. Results: Corneal trauma emerged as the most prevalent predisposing factor, accounting for 37.1% of cases. Among these cases, bacterial culture results were positive in 318 cases, 68 species of bacteria were identified. The most common Gram-Positive bacteria isolated overall was the staphylococcus epidermis and the most common Gram-Negative bacteria isolated was Pseudomonas aeruginosa. Methicillin-Resistant Staphylococci accounted for 18.1% of all Gram-Positive bacteria. The detection rate of P. aeruginosa showed an increasing trend over time (Rs=0.738, P=0.037). There was a significant decrease in the percentage of Gram-Negative microorganisms over time (Rs=0.743, P=0.035). The sensitivity of Gram-Positive bacteria to linezolid, vancomycin, tigecycline, quinupristin/dalfopristin, and rifampicin was over 98%. The sensitivity rates of Gram-Negative bacteria to amikacin, meropenem, piperacillin/tazobactam, cefoperazone sodium/sulbactam, ceftazidime, and cefepime were all above 85%. In patients with a history of vegetative trauma, the possibility of BK should be taken into account in addition to the focus on fungal keratitis. Conclusion: The microbial composition primarily consists of Gram-Positive cocci and Gram-Negative bacilli. Among the Gram-Positive bacteria, S. epidermidis and Streptococcus pneumoniae are the most frequently encountered, while P. aeruginosa is the predominant Gram-Negative bacteria. To combat Gram-Positive bacteria, vancomycin, linezolid, and rifampicin are considered excellent antimicrobial agents. When targeting Gram-Negative pathogens, third-generation cephalosporins exhibit superior sensitivity compared to first and second-generation counterparts. As an initial empirical treatment for severe cases of bacterial keratitis and those unresponsive to fourth-generation fluoroquinolones in community settings, the combination therapy of vancomycin and tobramycin is a justifiable approach. Bacterial keratitis can be better managed by understanding the local etiology and antibacterial drug susceptibility patterns.

Clinical pharmacist intervention in contraindications of the co-administration of cefoperazone and ambroxol hydrochloride injection.

BACKGROUND: Clinical pharmacists identified contraindications in two cases concerning the co-administration of cefoperazone and ambroxol hydrochloride injection, prompting a thorough investigation. CASE PRESENTATION: Clinically, two cases of contraindications for the co-administration of cefoperazone and ambroxol hydrochloride injection were discovered. After the intervention and analysis by clinical pharmacists, the possible reason could be the precipitation of free alkali due to the immediate administration of ambroxol after the infusion of cefoperazone. Clinical pharmacists suggested avoiding the co-administration of the two and recommended flushing the intravenous lines with 5% glucose injection or 0.9% sodium chloride injection during intravenous infusion to prevent direct drug interaction causing precipitation, thereby reducing the occurrence of adverse events. No adverse events occurred after the intervention, and no harm was caused to the patients. CONCLUSIONS: The co-administration of cefoperazone and ambroxol hydrochloride injection can lead to the precipitation of free alkali, posing a risk of adverse events. Clinical pharmacists' intervention could prevent this interaction. This practice has been shown to be effective, with no subsequent adverse events reported.

In-depth analysis of the treatment effect and synergistic mechanism of TanReQing injection on clinical multi-drug resistant Pseudomonas aeruginosa.

Antibiotic resistance is a recognized and concerning public health issue. Gram-negative bacilli, such as Pseudomonas aeruginosa (P. aeruginosa), are notorious for their rapid development of drug resistance, leading to treatment failures. TanReQing injection (TRQ) was chosen to explore its pharmacological mechanisms against clinical multidrug-resistant P. aeruginosa (MDR-PA), given its antibacterial and anti-inflammatory properties. We revealed the expression of proteins and genes in P. aeruginosa after co-culture with TRQ. This study developed an assessment method to evaluate clinical resistance of P. aeruginosa using MALDI-TOF MS identification and Biotyper database searching techniques. Additionally, it combined MIC determination to investigate changes in MDR-PA treated by TRQ. TRQ effectively reduced the MICs of ceftazidime and cefoperazone and enhanced the confidence scores of MDR-PA as identified by mass spectrometry. Using this evaluation method, the fingerprints of standard P. aeruginosa and MDR-PA were compared, and the characteristic peptide sequence (Seq-PA No. 1) associated with flagellum was found. The phenotypic experiments were conducted to confirm the effect of TRQ on the motility and adhesion of P. aeruginosa. A combination of co-immunoprecipitation and proteome analysis was employed, and 16 proteins were significantly differentially expressed and identified as potential candidates for investigating the mechanism of inhibiting resistance in P. aeruginosa treated by TRQ. The candidates were verified by quantitative real-time PCR analysis, and TRQ may affect these core proteins (MexA, MexB, OprM, OprF, OTCase, IDH, and ASL) that influence resistance of P. aeruginosa. The combination of multiple methods helps elucidate the synergistic mechanism of TRQ in overcoming resistance of P. aeruginosa.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen closely associated with various life-threatening acute and chronic infections. The presence of antimicrobial resistance and multidrug resistance in P. aeruginosa infections significantly complicates antibiotic treatment. The expression of ß-lactamase, efflux systems such as MexAB-OprM, and outer membrane permeability are considered to have the greatest impact on the sensitivity of P. aeruginosa. The study used a method to assess the clinical resistance of P. aeruginosa using matrix-assisted laser desorption ionization time of flight mass spectrometry identification and Biotyper database search techniques. TanReQing injection (TRQ) effectively reduced the MICs of ceftazidime and cefoperazone in multidrug-resistant P. aeruginosa (MDR-PA) and improved the confidence scores for co-cultured MDR-PA. The study found a characteristic peptide sequence for distinguishing whether P. aeruginosa is resistant. Through co-immunoprecipitation and proteome analysis, we explored the mechanism of TRQ overcoming resistance of P. aeruginosa.

Serum trough concentration threshold and risk factors of cefoperazone-induced coagulopathy in critically ill patients: A retrospective case-control study.

PURPOSE: To analyze the risk factors influencing the development of cefoperazone-induced coagulopathy in critically ill patients and determine the threshold of serum trough concentration. METHODS: A retrospective case-control study was conducted in the intensive care unit patients treated with cefoperazone, and it was approved by the Ethical Committee of Drum Tower Hospital affiliated with the Medical School of Nanjing University (NO.2023-158-01). Patients were divided into the normal group and coagulopathy group based on prothrombin time. The clinical characteristics of the two groups were compared using univariate analysis. The serum concentration threshold and influencing factors of cefoperazone-induced coagulopathy in critically ill patients were analyzed using the receiver operating characteristic curve and multivariate logistic regression analysis. RESULTS: A total of 113 patients were included, and cefoperazone-induced coagulopathy occurred in 39 patients, with an incidence of 34.5%. These patients experienced significant prothrombin time prolongation around day 6 (median) after cefoperazone application. The serum trough concentration threshold of cefoperazone-induced coagulopathy in critically ill patients was 87.765 mg/l. Multivariate logistic regression analysis revealed that the APACHE II score (p = 0.034), prophylactic use of vitamin K1 (p < 0.001), hepatic impairment (p = 0.014), and Cmin ≥ 87.765 mg/l (p = 0.005) were associated with cefoperazone-induced coagulopathy. CONCLUSION: Cefoperazone-induced coagulopathy usually occurs on the 6th day of cefoperazone use in critically ill patients. The risk will increase in patients with an APACHE II score > 25, hepatic impairment, and cefoperazone Cmin ≥ 87.765 mg/l. Vitamin K1 is effective in preventing this adverse reaction.

Efficacy of cefoperazone/sulbactam for ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and the factors associated with poor outcomes.

OBJECTIVE: We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. METHODS: This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. RESULTS: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15-29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45-141.82, P = 0.023). DISCUSSION: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality.

Antimicrobial susceptibility of mastitis pathogens isolated from North American dairy cattle, 2011-2022.

A total of 10,890 bacterial isolates of Streptococcus dysgalactiae, Streptococcus uberis, Staphylococcus aureus and Escherichia coli isolated as etiological agents from dairy cows with mastitis by 29 veterinary laboratories across North America between 2011 and 2022 were tested for in vitro antimicrobial susceptibility by broth microdilution to ampicillin, cefoperazone, ceftiofur, cephalothin, erythromycin, oxacillin, penicillin-novobiocin and pirlimycin according to CLSI standards. Using available clinical breakpoints, antimicrobial resistance among S. dysgalactiae (n = 2406) was low for penicillin-novobiocin (0% resistance), ceftiofur (0.1%), erythromycin (3.2%) and pirlimycin (4.6%). Among S. uberis (n = 2398), resistance was low for ampicillin (0%) and ceftiofur (0.2%) and moderate for erythromycin (11.9%) and pirlimycin (18.4%). For S. aureus (n = 3194), resistance was low for penicillin-novobiocin (0%), ceftiofur (0.1%), oxacillin (0.2%), erythromycin (0.7%), cefoperazone (1.2%) and pirlimycin (2.8%). For E. coli (n = 2892), resistance was low for ceftiofur (2.8%) and cefoperazone (3.4%) and moderate for ampicillin (9.2%). Overall, the results indicate that mastitis pathogens in the United States and Canada have not shown any substantial changes in the in vitro susceptibility to antimicrobial drugs over the 12 years of the study, or among that of the proceeding survey from 2002-2010. The data support the conclusion that resistance to common antimicrobial drugs among mastitis pathogens, even to drugs that have been used in dairies for mastitis management for many years, continues to remain low.

A case of Elizabethkingia meningoseptica septicemia. / 脑膜脓毒性伊丽莎白金菌败血症一例.

A 82-year-old man was admitted to hospital with fever, unresponsiveness, elevated hypersensitive C-reactive protein and neutrophile granulocyte. Ceftriaxone was administrated by intravenous dripping in the emergency room, but the effect was not satisfactory. Following his admission to the ward, cefoperazone sulbactam were given. Elizabethkingia meningoseptica was identified by blood culture and further confirmed by 16S rRNA sequencing. The lumbar puncture showed that cerebrospinal fluid pressure was 80 mmH2O (1 mmH2O=0.0098 kPa) and biochemical results were normal. After 11 days of cefoperazone sulbactam treatment, the patient was discharged with negative blood culture. The hypersensitive C-reactive protein and neutrophile granulocyte had also declined. The patient received levofloxacin tablets for anti-infection treatment for 14 d after discharge. No signs of infection were observed in three months' following up.

Accuracy of antibiotic concentrations in drug dispensing in neonates: a laboratory-based study.

BACKGROUND: Antibacterial therapy plays a crucial role in neonatal infections. The efficacy of antibacterial agents is closely related to the actual dose given to neonates. So we evaluated factors potentially affecting the actual dose of intravenous antibiotics during dispensing process in neonates. METHODS: Meropenem, cefoperazone/sulbactam and piperacillin/tazobactam with two strengths were used to evaluate three methods. Method A (MA) was diluted once and the volumes of 5% glucose for MA were meropenem 4.00 mL, cefoperazone/sulbactam 3.00 mL, piperacillin/tazobactam 9.00 mL. Method B (MB) differed by doubling the volume of 5% glucose. The difference in method C (MC) involved diluting with 5% glucose twice. The concentrations were measured by high-performance liquid chromatography. Relative error (RE) was used to evaluate the preparation accuracy. RESULTS: The RE values using MA/MB/MC were: (1) meropenem 0.5 g: 15.1%, 8.0%, 10.4%; 0.25 g: 7.8%, 3.1%, 6.0%; (2) cefoperazone/sulbactam 1.5 g: 13.6%, 4.2%, 3.4%; 0.75 g: 8.8%, 3.5%, 4.0%; (3) piperacillin/tazobactam 4.5 g: 18.2%, 8.7%, 6.3%; 562.5 mg: 8.1%, 2.8%, 6.1%. MB was better than MA in all three drugs. No difference in RE values was found between single and double dilution, except meropenem with 0.25 g. Using MB, meropenem and piperacillin/tazobactam with small drug strength had higher accuracy in preparation. CONCLUSIONS: MB was suitable for neonatal drug dispensing because of its high accuracy and simple operation. Drugs with small strength were promoted due to the high accuracy.

Safety of Tigecycline in Patients on Antithrombotic Therapy: A Single-Center Retrospective Study.

INTRODUCTION: The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs. METHODS: We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without. RESULTS: This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline. CONCLUSION: A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment.

Development and validation of a nomogram for predicting cefoperazone/sulbactam-induced hypoprothrombinaemia in Hospitalized adult patients.

Cefoperazone/sulbactam-induced hypoprothrombinaemia is associated with longer hospital stays and increased risk of death. The aim of this study was to develop and validate a nomogram for predicting the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia in hospitalized adult patients. This retrospective cohort study involved hospitalized adult patients at Xi'an Central Hospital from January 2020 to December 2022 based on the Chinese pharmacovigilance system developed and established by the Adverse Drug Reaction Monitoring Center in China. Independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were obtained using multivariate logistic regression and were used to develop and establish the nomogram. According to the same standard, the clinical data of hospitalized patients using cefoperazone/sulbactam at the Third Affiliated Hospital of Xi'an Medical University from January 1, 2023 to June 30, 2023 were collected as the external validation group. The 893 hospitalized patients included 95 who were diagnosed with cefoperazone/sulbactam-induced hypoprothrombinaemia. Our study enrolled 610 patients: 427 in the training group and 183 in the internal validation group. The independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were surgery (odds ratio [OR] = 5.279, 95% confidence interval [CI] = 2.597-10.729), baseline platelet count ≤50×109/L (OR = 2.492, 95% CI = 1.110-5.593), baseline hepatic dysfunction (OR = 12.362, 95% CI = 3.277-46.635), cumulative defined daily doses (OR = 1.162, 95% CI = 1.162-1.221) and nutritional risk (OR = 16.973, 95% CI = 7.339-39.254). The areas under the curve (AUC) of the receiver operating characteristic for the training and internal validation groups were 0.909 (95% CI = 0.875-0.943) and 0.888 (95% CI = 0.832-0.944), respectively. The Hosmer-Lemeshow tests yielded p = 0.475 and p = 0.742 for the training and internal validation groups, respectively, confirming the goodness of fit of the nomogram model. In the external validation group (n = 221), the nomogram was equally robust in cefoperazone/sulbactam-induced hypoprothrombinaemia (AUC = 0.837, 95%CI = 0.736-0.938). The nomogram model constructed in this study had good predictive performance and extrapolation, which can help clinicians to identify patients at high risk of cefoperazone/sulbactam-induced hypoprothrombinaemia early. This will be useful in preventing the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia and allowing timely intervention measures to be performed.

Case report: A rare multidrug-resistant Escherichia coli causes fatal neonatal meningoencephalitis.

Neonatal meningitis is rare but devastating disease. Multidrug-resistant (MDR, multi-drug resistant) bacteria are a major global health risk. We report an Escherichia coli meningitis isolate with multiple resistance patterns and unusual serotype (O75) that caused sudden neonatal death. The isolate was resistant to antibiotics other than cefoperazone/sulbactam and imipenem, challenging the combination of antibiotics commonly used in the empirical treatment of neonatal sepsis. Despite aggressive symptomatic and supportive treatment of the infant based on laboratory tests and clinical practice, the infant eventually died. This is the first case of meningoencephalitis due to serotype O75 reported in China. The presence of highly pathogenic multidrug-resistant microorganisms isolated in neonates underscores the need to implement rapid resistance diagnostic methods and should prompt consideration of alternatives to empiric treatment of neonatal bacterial meningitis.

[A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies].

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Probing the interaction of cephalosporin antibiotic "cefoperazone" with lysozyme using spectroscopic and in silico methods: Effect of paracetamol on binding.

The interaction of lysozyme with cefoperazone was studied by means of spectroscopic and computational approaches. The change in the UV-visible spectrum of lysozyme in presence of cefoperazone was an indication of the complex formation between them. Fluorescence spectroscopy suggested that there was a fair interaction between the protein and drug which was taken place via dynamic quenching mechanism and the binding ratio was approximately 1:1. The binding was energetically feasible and principally supported by the hydrophobic forces. CD spectroscopic studies have shown that cefoperazone induced the secondary structure of lysozyme by increasing the α-helical contents of the latter. In silico studies revealed that the large nonpolar cavity was the preferred binding site of cefoperazone within lysozyme and the interaction was taken place mainly through hydrophobic forces with small involvement of hydrogen bonding and electrostatic interactions which is in good agreement with the experimental analyses. Effect of paracetamol was also seen on the binding and it was found that paracetamol had a negative influence on the binding between cefoperazone and lysozyme.

The clinical efficacy of cefoperazone-sulbactam versus piperacillin-tazobactam in the treatment of severe community-acquired pneumonia.

The objective was to compare the clinical efficacy of cefoperazone-sulbactam with piperacillin-tazobactam in the treatment of severe community-acquired pneumonia (SCAP). The retrospective study was conducted from March 1, 2018 to May 30, 2019. Clinical outcomes were compared for patients who received either cefoperazone-sulbactam or piperacillin-tazobactam in the treatment of SCAP. A total of 815 SCAP patients were enrolled. Among them, 343 received cefoperazone-sulbactam, and 472 received piperacillin-tazobactam. Patients who received cefoperazone-sulbactam presented with higher Charlson Comorbidity Index scores. (6.20 ± 2.77 vs 5.72 ± 2.61; P = .009). The clinical cure rates and effectiveness for patients receiving cefoperazone-sulbactam and piperacillin-tazobactam were 84.2% versus 80.3% (P = .367) and 85.4% versus 83.3% (P = .258), respectively. In addition, the overall mortality rate of the cefoperazone-sulbactam group was 16% (n = 55), which was also comparable to the piperacillin-tazobactam group (17.8%, n = 84, P = .572). The primary clinical outcomes for patients receiving cefoperazone-sulbactam were superior compared to those receiving piperacillin-tazobactam after adjusting disease severity status. The clinical efficacy of cefoperazone-sulbactam in the treatment of adult patients with SCAP is comparable to that of piperacillin-tazobactam. After adjusting for disease severity, cefoperazone-sulbactam tended to be superior to piperacillin-tazobactam.