Development and internal validation of a model for predicting cefoperazone/sulbactam-associated coagulation disorders in Chinese inpatients.

BACKGROUND AND AIM: The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients. METHODS: A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn't develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings. RESULTS: 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8%. A final population of 252 cases and 252 controls was included for model development and validation. Malnutrition (OR = 2.41 (1.56-3.77)), history of recent bleeding (OR = 1.95 (1.32-2.90)), treatment duration (OR = 1.10 (1.07-1.14)), combination with carbapenems (OR = 4.43 (1.85-11.88)), and serum creatinine (OR = 1.01 (1.00-1.01)) were identified as final predictors. The model showed good discrimination, calibration, and clinical practicality, with the validated area under the receiver operating characteristic curve being 0.723 (0.683-0.770). CONCLUSIONS: The model with good performance quantifies the risk for CPZ/SAM-associated coagulation disorders, and may support individual assessment and interventions to mitigate the risk after external validation.

A phase II, multicenter, nonblinded, randomized controlled trial for evaluating protective effects of ABPC/SBT plus, azithromycin versus erythromycin, in pregnant women with pPROM occurring at <28 weeks of gestation on the development of BPD in neonates: Study protocol.

This is a protocol for PPROM-AZM Study, phase II, nonblinded, randomized controlled trial. Bronchopulmonary dysplasia (BPD) at a postmenstrual age of 36 weeks (BPD36) is often observed in infants with preterm premature rupture of the membranes (pPROM). A regimen of ampicillin (ABPC) intravenous infusion for 2 days and subsequent amoxicillin (AMPC) oral administration for 5 days plus erythromycin (EM) intravenous infusion for 2 days followed by EM oral administration for 5 days is standard treatment for pPROM. However, the effect on the prevention of moderate/severe BPD36 using the standard treatment has not been confirmed. Recently, it is reported that ampicillin/sulbactam (ABPC/SBT) plus azithromycin (AZM) was effective for the prevention of moderate/severe BPD36 in pPROM patients with amniotic infection of Ureaplasma species. Therefore, our aim is to evaluate the occurrence rate of the composite outcome of "incidence rate of either moderate/severe BPD36 or intrauterine fetal death, and infantile death at or less than 36 weeks 0 days" comparing subjects to receive ABPC/SBT for 14 days plus AZM for 14 days (intervention group) and those to receive ABPC/SBT for 14 days plus EM for 14 days (control group), in a total of 100 subjects (women with pPROM occurring at 22-27 weeks of gestation) in Japan. The recruit of subjects was started on April 2022, and collection in on-going. We also investigate the association between the detection of Ureaplasma species and occurrence of BPD36. In addition, information on any adverse events for the mother and fetus and serious adverse events for infants are collected during the observation period. We allocate patients at a rate of 1:1 considering two stratification factors: onset of pPROM (22-23 or 24-27 weeks) and presence/absence of a hospital policy for early neonatal administration of caffeine. Trial registration: The trial number in the Japan Registry of Clinical Trials is jRCTs031210631.

Role of the gut microbiota in cefoperazone/sulbactam-induced epilepsy in mice with chronic renal failure.

OBJECTIVES: The mechanism of cefoperazone/sulbactam-induced epilepsy in chronic kidney disease (CKD) patients is not yet clear. We hypothesized that cefoperazone/sulbactam-induced epilepsy could be based on two main factors: neurotoxicity caused by drug accumulation after renal failure and an abnormal gut microbiota (GM). METHODS: A chronic renal failure (CRF) model in mice was established, and then different doses of cefoperazone/sulbactam were injected to induce epilepsy in mice. Normal mouse feces for fecal microbiota transplantation (FMT) were collected. We observed the changes in feces, mental state, and activity of each group of mice. After killing, we collected kidneys and colon for H&E staining. We collected mouse feces for the 16S RNA sequencing of bacteria. RESULTS: All CRF mice injected with different concentrations of cefoperazone/sulbactam experienced grade-V seizures and eventually died, whereas normal control mice did not. However, after FMT intervention, the time of epilepsy onset and death in mice was delayed. Early FMT intervention resulted in more mice surviving (p = .0359). Moreover, the villi in the mucosal of group-CS layer fell off, goblet cells missed, and crypts disappeared. The mucosal layer and submucosa were clearly separated. The morphology of intestinal tissue of the CFS and FS group was improved. After FMT, the changes of the GM were observed. CONCLUSIONS: The GM may be involved in the epilepsy induced by cefoperazone/sulbactam in CRF mice. FMT can delay the onset of epilepsy in CRF mice induced by cefoperazone/sulbactam, and the earlier the intervention, the better the effect.

Intravenous fosfomycin for treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: A multi-centre clinical experience.

BACKGROUND: Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections. METHODS: This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model. RESULTS: One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48) or ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, early 24-h active in-vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success. CONCLUSIONS: Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB.

Treatment-emergent cefiderocol resistance in carbapenem-resistant Acinetobacter baumannii is associated with insertion sequence ISAba36 in the siderophore receptor pirA.

We report the emergence of cefiderocol resistance in a blaOXA-72 carbapenem-resistant Acinetobacter baumannii isolate from a sacral decubitus ulcer. Cefiderocol was initially used; however, a newly approved sulbactam-durlobactam therapy with source control and flap coverage was successful in treating the infection. Laboratory investigation revealed cefiderocol resistance mediated by ISAba36 insertion into the siderophore receptor pirA.

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.

In vitro antibacterial activity of sulbactam-durlobactam in combination with other antimicrobial agents against Acinetobacter baumannii-calcoaceticus complex.

Combinations of the ß-lactam/ß-lactamase inhibitor sulbactam-durlobactam and seventeen antimicrobial agents were tested against strains of Acinetobacter baumannii in checkerboard assays. Most combinations resulted in indifference with no instances of antagonism. These results suggest sulbactam-durlobactam antibacterial activity against A. baumannii is unlikely to be affected if co-dosed with other antimicrobial agents.

A Comprehensive Study to Determine the Residual Elimination Pattern of Major Metabolites of Amoxicillin-Sulbactam Hybrid Molecules in Rats by UPLC-MS/MS.

Amoxicillin and sulbactam are widely used in animal food compounding. Amoxicillin-sulbactam hybrid molecules are bicester compounds made by linking amoxicillin and sulbactam with methylene groups and have good application prospects. However, the residual elimination pattern of these hybrid molecules in animals needs to be explored. In the present study, the amoxicillin-sulbactam hybrid molecule (AS group) and a mixture of amoxicillin and sulbactam (mixture group) were administered to rats by gavage, and the levels of the major metabolites of amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and sulbactam were determined by UPLC-MS/MS. The residue elimination patterns of the major metabolites in the liver, kidney, urine, and feces of rats in the AS group and the mixture group were compared. The results showed that the total amount of amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and the highest concentration of sulbactam in the liver and kidney samples of the AS group and the mixture group appeared at 1 h after drug withdrawal. Between 1 h and 12 h post discontinuation, the total amount of amoxicillin, amoxicilloic acid, and amoxicillin diketopiperazine in the two tissues decreased rapidly, and the elimination half-life of the AS group was significantly higher than that in the mixture group (p < 0.05); the residual amount of sulbactam also decreased rapidly, and the elimination half-life was not significantly different (p > 0.05). In 72 h urine samples, the total excretion rates were 60.61 ± 2.13% and 62.62 ± 1.73% in the AS group and mixture group, respectively. The total excretion rates of fecal samples (at 72 h) for the AS group and mixture group were 9.54 ± 0.26% and 10.60 ± 0.24%, respectively. These results showed that the total quantity of amoxicillin, amoxicilloic acid, and amoxicillin diketopiperazine was eliminated more slowly in the liver and kidney of the AS group than those of the mixture group and that the excretion rate through urine and feces was essentially the same for both groups. The residual elimination pattern of the hybrid molecule in rats determined in this study provides a theoretical basis for the in-depth development and application of hybrid molecules, as well as guidelines for the development of similar drugs.

Characterization of Acinetobacter baumannii-calcoaceticus complex isolates and microbiological outcome for patients treated with sulbactam-durlobactam in a phase 3 trial (ATTACK).

Acinetobacter baumannii-calcoaceticus complex (ABC) causes severe, difficult-to-treat infections that are frequently antibiotic resistant. Sulbactam-durlobactam (SUL-DUR) is a targeted ß-lactam/ß-lactamase inhibitor combination antibiotic designed to treat ABC infections, including those caused by multidrug-resistant strains. In a global, pathogen-specific, randomized, controlled phase 3 trial (ATTACK), the efficacy and safety of SUL-DUR were compared to colistin, both dosed with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC. Results from ATTACK showed that SUL-DUR met the criteria for non-inferiority to colistin for the primary efficacy endpoint of 28-day all-cause mortality with improved clinical and microbiological outcomes compared to colistin. This report describes the characterization of the baseline ABC isolates from patients enrolled in ATTACK, including an analysis of the correlation of microbiological outcomes with SUL-DUR MIC values and the molecular drivers of SUL-DUR resistance.

Evolution, control and success of combination therapy with Ampicilin-sulbactam/Ceftazidime-Avibactam during a Carbapenem-Resistant Acinetobacter baumannii outbreak in burn Intensive Care Unit.

We present our findings on interpatient transmission, epidemic control measures, and the outcomes of a series of ten critically ill burn patients who were either colonized or infected with carbapenem-resistant Acinetobacter baumannii (CRAB). None of the five infected patients achieved clinical cure, and all experienced relapses. Microbiological failure was observed in 40% of the infected patients. The isolated CRAB strains were found to carry blaOXA-23 and armA resistance genes. Despite the lack of clinical cure, all five infected patients survived and were discharged from the Burn Intensive Care Unit.

A Rare Cause of Coagulopathy in the Emergency Department: Cefoperazone Use.

Cefoperazone (CPZ) is an antibiotic widely used for moderate to severe infections, especially in countries where resources are difficult to access. This case report aimed to draw attention to coagulopathy, a potential side effect of CPZ. This side effect can cause high mortality and morbidity in patients. In the mechanism of CPZ causing coagulopathy, it is reported that effects such as binding to vitamin K, disrupting vitamin K metabolism, and preventing platelet aggregation are responsible. In this presentation, a case who came to the emergency department with the complaint of hematuria caused by coagulopathy after the use of CPZ-containing antibiotics (CPZ + sulbactam) is presented.

NMR insights into ß-Lactamase activity of UVI31+ Protein from Chlamydomonas reinhardtii.

ß-Lactamases (EC 3.5.2.6) confer resistance against ß-lactam group-containing antibiotics in bacteria and higher eukaryotes, including humans. Pathogenic bacterial resistance against ß-lactam antibiotics is a primary concern for potential therapeutic developments and drug targets. Here, we report putative ß-lactamase activity, sulbactam binding (a ß-lactam analogue) in the low µM affinity range, and site-specific interaction studies of a 14 kDa UV- and dark-inducible protein (abbreviated as UVI31+, a BolA homologue) from Chlamydomonas reinhartii. Intriguingly, the solution NMR structure of UVI31 + bears no resemblance to other known ß-lactamases; however, the sulbactam binding is found at two sites rich in positively charged residues, mainly at the L2 loop regions and the N-terminus. Using NMR spectroscopy, ITC and MD simulations, we map the ligand binding sites in UVI31 + providing atomic-level insights into its ß-lactamase activity. Current study is the first report on ß-lactamase activity of UVI31+, a BolA analogue, from C. reinhartii. Furthermore, our mutation studies reveal that the active site serine-55 is crucial for ß-lactamase activity.

Sulbactam-durlobactam: a ß-lactam/ß-lactamase inhibitor combination targeting Acinetobacter baumannii.

Sulbactam-durlobactam is a pathogen-targeted ß-lactam/ß-lactamase inhibitor combination that has been approved by the US FDA for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex (ABC) in patients 18 years of age and older. Sulbactam is a penicillin derivative with antibacterial activity against Acinetobacter but is prone to hydrolysis by ß-lactamases encoded by contemporary isolates. Durlobactam is a diazabicyclooctane ß-lactamase inhibitor with activity against Ambler classes A, C and D serine ß-lactamases that restores sulbactam activity both in vitro and in vivo against multidrug-resistant ABC. Sulbactam-durlobactam is a promising alternative therapy for the treatment of serious Acinetobacter infections, which can have high rates of mortality.

Sulbactam­durlobactam: a drug for treating lung infectionsAcinetobacter is a type of bacteria. One type, called CRAB, causes serious infections and can be fatal. CRAB is very hard to treat because most drugs no longer work. Sulbactam­durlobactam (SUL-DUR) is a drug that can kill CRAB. The US FDA approved SUL-DUR in May of 2023 for treating lung infections (pneumonia) caused by CRAB. This article explains how SUL-DUR works. Use of SUL-DUR and other drugs to treat these types of infections are discussed. In conclusion, SUL-DUR is a promising therapy for serious infections caused by CRAB.

[New awareness for zoonoses using the example of rat bite fever : Case report and literature review]. / Neue Achtsamkeit für Zoonosen am Beispiel Rattenbissfieber : Fallbericht und Literaturübersicht.

BACKGROUND: Rat bite fever is a rare but potentially fatal bacterial zoonosis. The symptoms can be unspecific, but severe sepsis can be associated with involvement of different organs. CASE REPORT: A 27-year-old homeless man presented with fever, suspected meningitis, acute renal failure, unclear skin lesions as well as joint problems and muscular pain. Bite wounds were not detected. Meningitis could be excluded after lumbar puncture, and there was no evidence of endocarditis as the cause of the skin lesions. After 72 h, growth of Streptobacillus moniliformis in blood cultures was detected. Clinical symptoms were compatible with the diagnosis of rat bite fever. Calculated antibiosis with ampicillin sulbactam and doxycycline led to regression of the symptoms. CONCLUSION: Rat bite fever poses a diagnostic challenge due unspecific symptoms, diverse differential diagnostic options, and challenging microbiological detection. Patient history is of the utmost importance. Due to the rarity of the disease, this case report is intended to raise awareness.

In vitro activity of apramycin (EBL-1003) in combination with colistin, meropenem, minocycline or sulbactam against XDR/PDR Acinetobacter baumannii isolates from Greece.

OBJECTIVES: To evaluate the in vitro activity of the combination of apramycin with colistin, meropenem, minocycline or sulbactam, against some well-characterized XDR Acinetobacter baumannii clinical isolates from Greece, to understand how apramycin can be best incorporated into clinical practice and optimize effectiveness. METHODS: In vitro interactions of apramycin (0.5×, 1× and 2× the MIC value) with colistin (2 mg/L), meropenem (30 mg/L), minocycline (3.5 mg/L) or sulbactam (24 mg/L) were tested using time-kill methodology. Twenty-one clinical A. baumannii isolates were chosen, exhibiting apramycin MICs of 4-16 mg/L, which were at or below the apramycin preliminary epidemiological cut-off value of 16 mg/L. These isolates were selected for a range of colistin (4-32 mg/L), meropenem (16-256 mg/L), minocycline (8-32 mg/L) and sulbactam (8-32 mg/L) MICs across the resistant range. Synergy was defined as a ≥2 log10 cfu/mL reduction compared with the most active agent. RESULTS: The combination of apramycin with colistin, meropenem, minocycline or sulbactam was synergistic, at least at one of the concentrations of apramycin (0.5×, 1× or 2× MIC), against 83.3%, 90.5%, 90.9% or 92.3% of the tested isolates, respectively. Apramycin alone was bactericidal at 24 h against 9.5% and 33.3% of the tested isolates at concentrations equal to 1× and 2× MIC, while the combination of apramycin at 2× MIC with colistin, meropenem or sulbactam was bactericidal against all isolates tested (100%). The apramycin 2× MIC/minocycline combination had bactericidal activity against 90.9% of the tested isolates. CONCLUSIONS: Apramycin combinations may have potential as a treatment option for XDR/pandrug-resistant (PDR) A. baumannii infections and warrant validation in the clinical setting, when this new aminoglycoside is available for clinical use.

Clinical characteristics and risk factors for Klebsiella pneumoniae bloodstream infection in 152 immunocompetent patients.

OBJECTIVE: To investigate the clinical characteristics and prognostic risk factors for Klebsiella pneumoniae bloodstream infections in immunocompetent patients. METHODS: The study included patients with K. pneumoniae bloodstream infection treated in Zhongda Hospital from June 2016 to June 2021. Clinical data and antibiotic susceptibility test results were retrospectively collected and analyzed. Independent risk factors for mortality were screened using the chi-square test and multivariate logistic regression. RESULTS: A total of 152 patients were included in the analysis. In our cohort, 77.6% of patients were older than 60 years, and 80.9% of them had community-acquired infections. The most common complications were type 2 diabetes, hypertension, and stroke sequelae. The proportion of patients with septic shock or abscesses was 34.9% and 25.7%, respectively. There were significant differences in the site of infection, septic shock, and serum levels of procalcitonin, hypersensitive C-reactive protein, D-dimer, creatinine, and lactic acid between survivors and non-survivors (p < 0.05). Multivariate regression analysis showed that hospital-acquired infections, septic shock, length of hospital stay, and creatinine levels were independent risk factors for mortality. Antibiotic susceptibility test results indicated that clinical outcomes varied depending on bacterial sensitivity to ampicillin/sulbactam. DISCUSSION: Klebsiella pneumoniae is a common community-acquired and hospital-acquired bacteria and usually infects older people with complications such as diabetes. Nosocomial infections, length of stay, septic shock, and renal insufficiency are potentially associated with poor prognosis. Bacterial susceptibility to ampicillin/sulbactam affects prognosis.

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.

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.