ATAK complex (adrenaline, takotsubo, anaphylaxis, and kounis hypersensitivity-associated coronary syndrome) related to latamoxef administration-a case report.

Background: Adrenaline, stress cardiomyopathy, allergic reactions, and Kounis syndrome (Adrenaline, Takotsubo, Anaphylaxis, Kounis Complex, ATAK) constitute a complex clinical syndrome often associated with endogenous or exogenous adrenaline. Due to its rapid onset, severity, and treatment challenges, it warrants significant attention from clinicians. This article reports a case of Type II Kounis syndrome combined with stress cardiomyopathy (ATAK) triggered by a latamoxef-induced allergy. Case report: A 67-year-old male patient with an acute exacerbation of chronic obstructive pulmonary disease was admitted to the respiratory department for treatment. The day before discharge, after receiving a latamoxef infusion for 27 min, the patient developed wheezing, dyspnea, chills, profuse sweating, and an elevated body temperature, necessitating transfer to the ICU for monitoring and treatment. The ECG suggested a suspected myocardial infarction, while bedside echocardiography showed a left ventricular ejection fraction of 40%, segmental dysfunction of the left ventricle, and apical rounding. Emergency coronary angiography revealed 50% segmental eccentric stenosis in the mid-segment of the left anterior descending branch and right coronary artery. The final diagnosis was Type II Kounis Syndrome combined with stress cardiomyopathy due to a latamoxef-induced allergy, i.e., ATAK. Despite aggressive treatment, the patient succumbed to severe cardiogenic shock on the third day in the ICU. Conclusion: ATAK is a critical condition that progresses rapidly. For patients experiencing severe allergic reactions, monitoring biomarkers such as Troponin and ECG changes is crucial for timely recognition. If a patient is diagnosed with Kounis syndrome, caution should be exercised in using adrenaline to prevent ATAK.

Estimation of latamoxef (moxalactam) dosage regimens against ß-lactamase-producing Enterobacterales in dogs: a pharmacokinetic and pharmacodynamic analysis using Monte Carlo simulation.

One of the most significant research areas in veterinary medicine is the search for carbapenem substitutes for the treatment of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (ESBL-E). This study applied a pharmacokinetic/pharmacodynamic (PK/PD) strategy in validating optimal latamoxef (LMX) therapeutic regimens against canine ESBL-E infections. Five dogs were administered a bolus dose of 40 mg/kg LMX intravenously to measure serum drug concentrations and determine PK indices using the noncompartmental model. The highest minimum inhibitory concentration (MIC) with a probability of target attainment ≥90% was used to compute the PK/PD cutoff values for bacteriostatic (time for which the unbound drug concentration was above the MIC [fTAM] ≥ 40%) and bactericidal (fTAM ≥ 70%) effects when administered at 20, 30, 50, and 60 mg/kg, in addition to 40 mg/kg. The cumulative fraction of response (CFR) was determined using the MIC distribution of wild-type ESBL-E in companion animals. The PK/PD cutoff values can be increased by reducing the dosing interval rather than increasing the dose per time. Based on the calculated CFRs for ESBL-producing Escherichia coli and Klebsiella pneumoniae, all LMX regimens in this study and those administered at 30-60 mg/kg every 8 and 6 hr were found to be optimal (CFR ≥ 90%) for exerting bacteriostatic and bactericidal effects, respectively. However, the regimens of 50 and 60 mg/kg every 6 hr may merely exert bacteriostatic effects on ESBL-producing Enterobacter cloacae. Further clinical trials are required to confirm the clinical efficacy of LMX.

Latamoxef dosing regimen adjustments and pharmaceutical care in pediatrics.

Latamoxef is a semi-synthetic, broad-spectrum oxacephem antibiotic used primarily to treat infectious diseases, but the adverse drug reactions, such as the risk of fatal bleeding, once caused physicians to use it less frequently. However, with the rise of antibiotic-resistant bacterial strains, latamoxef is being used again to treat infectious diseases, especially in pediatrics. The pharmacokinetic parameters of latamoxef are highly variable, given the changes in body composition, organ maturation, and development that occurs in pediatrics. Therefore, an appropriate dosing regimen is essential. Latamoxef dosing optimization in pediatrics should adequately account for current body weight, postnatal age, postmenstrual age, and different minimum inhibitory concentration (MIC) values. In addition, attention should also be paid to some of the adverse reactions associated with latamoxef, such as coagulation disorders and bleeding risks, disulfiram-like reactions, as well as hypersensitivity and anaphylactic shock. This review summarizes the dosing regimens and some key points of pharmaceutical care for latamoxef in pediatrics in order to provide a better reference for its application in clinical practice.

Latamoxef-induced severe thrombocytopenia during the treatment of pulmonary infection: A case report.

BACKGROUND: Latamoxef shows excellent antibacterial activity against anaerobic bacteria such as Bacteroides fragilis. Reports of thrombocytopenic toxicity of latamoxef are limited. This report presents a case of severe thrombocytopenia possibly induced by latamoxef, an infrequent adverse drug reaction in a young patient with tuberculosis and Crohn's disease in China. CASE SUMMARY: We reported a case of severe thrombocytopenia induced by latamoxef in a 28-year-old man with tuberculosis and Crohn's disease. On admission, the patient presented with a cough productive of bloody sputum, a chest computed tomogram suggested scattered mottled, high-density shadows in both lungs. Laboratory tests indicated a platelet count of 140000/µL. Considered a pulmonary bacterial infection, the patient received anti-infection therapy with latamoxef (dose: 2.0 g) intravenously Q12h. On the 9th day of treatment, the platelet count decreased to 44000/µL. On the 12th day, scattered purpura and ecchymosis appeared on the patient's limbs and trunk, and the platelet count decreased to 9000/µL after latamoxef treatment for 15 d. Three days after discontinuation of latamoxef, the platelet count recovered to 157000/µL, and the area of scattered purpura and ecchymosis on the limbs and trunk decreased. The platelet counts remained in the normal range, and no thrombocytopenia was found at follow-up 15 mo after discharge. CONCLUSION: For patients treated with latamoxef, platelet counts should be carefully followed, and caregivers should be vigilant for the appearance of scattered ecchymosis.

Population Pharmacokinetics and Dosing Regimen Optimization of Latamoxef in Chinese Children.

The present study aimed to establish population pharmacokinetic models of latamoxef, as well as its R- and S-epimers, and generate findings to guide the individualized administration of latamoxef in pediatric patients. A total of 145 in-hospital children aged 0.08-10.58 years old were included in this study. Three population pharmacokinetic models of latamoxef and its R- and S-epimers were established. The stability and predictive ability of the final models were evaluated by utilizing goodness-of-fit plots, nonparametric bootstrapping, and normalized prediction distribution errors. The final model of total latamoxef was considered as a basis for the dosing regimen. A two-compartment model with first-order elimination best described the pharmacokinetics of total latamoxef. The population typical values of total latamoxef were as follows: central compartment distribution volume (V1) of 4.84 L, peripheral compartment distribution volume (V2) of 16.18 L, clearance (CL) of 1.00 L/h, and inter-compartmental clearance (Q) of 0.97 L/h. Moreover, R-epimer has a higher apparent volume of distribution and lower clearance than S-epimer. Body surface area (BSA) was identified as the most significant covariate to V, CL, and Q. Specific recommendations are given for dosage adjustment in pediatric patients based on BSA. This study highlights that a BSA-normalized dose of latamoxef was required when treating different bacteria to reach the therapeutic target more effectively.

Latamoxef-induced coagulation disorders: Incidence and risk factors.

WHAT IS KNOWN AND OBJECTIVE: To observe the effect of latamoxef on coagulation function and to analyse its risk factors. METHODS: A retrospective cohort study was performed to compare patients receiving latamoxef versus those treated with ceftazidime. Baseline characteristics and coagulation parameters were recorded and analysed to explore whether treatment with latamoxef increased the risks of coagulation disorders and bleeding. RESULTS AND DISCUSSION: A total number of 162 patients receiving latamoxef and 93 patients receiving ceftazidime were included. Haemorrhagic events were similar between groups, but patients receiving latamoxef had a higher risk of coagulation disorders compared to those receiving ceftazidime. Multivariate analysis revealed that the exposure of antibiotics, especially the cumulative defined daily doses (DDDs), and the nutrition risk may be the predictors of coagulation disorders. WHAT IS NEW AND CONCLUSION: Latamoxef might induce coagulation disorders. Cumulative DDDs and the nutrition risk were linked with coagulation disorders.

Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial.

Early-onset neonatal sepsis (EONS), a bacterial infection that occurs within 72 h after birth, is associated with high likelihood of neonatal mortality. Latamoxef, a semi-synthetic oxacephem antibiotic developed in 1980s, has been brought back into empirical EONS treatment in recent years. In the preliminary work, we established a population pharmacokinetics (PPK) model for latamoxef in Chinese neonates. Moreover, in order to better guide clinical treatment, we conducted dose simulation and found that ascending administration frequency could improve the target rate of 70% of patients having a free antimicrobial drug concentration exceeding the MIC during 70% of the dosing interval (70% fT > MIC). Accordingly, this study is aimed to compare the 70% fT > MIC, efficacy and safety between conventional regimen and PPK model regimen for rational use of latamoxef in EONS treatment. A single-blind, multicenter randomized controlled trial (RCT) for latamoxef will be conducted in Chinese EONS patients. Neonates (≤3 days of age, expected number = 114) admitted to the hospital with the diagnosis of EONS and fulfilling inclusion and exclusion criteria will be randomized (ratio of 1:1) to either a conventional regimen (30 mg/kg q12h) or model regimen (20 mg/kg q8h) latamoxef treatment group for at least 3 days. Primary outcome measure will be 70% fT > MIC and secondary outcome indicators will be the latamoxef treatment failure, duration of antibiotic therapy, changes of white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT), blood culture results during administration and incidence of adverse event (AE)s. Assessments will be made at baseline, initial stage of latamoxef treatment (18-72 h) and before the end of latamoxef treatment. Ethical approval of our clinical trial has been granted by the ethics committee of the Beijing Children's Hospital (ID: 2020-13-1). Written informed consent will be obtained from the parents of the participants. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR 2000040064).It is hoped that our study will provide a clinical basis for the rational clinical use of latamoxef in EONS treatment.

Latamoxef induced a severe coagulation disorder in older patients in China: Two case reports.

WHAT IS KNOWN AND OBJECTIVE: We present two cases of severe coagulation disorders induced by latamoxef, thereby revealing risk factors of coagulation disorder in latamoxef-treated patients. CASE SUMMARY: Two very elderly patients developed haemorrhage, and coagulation tests showed a longer prothrombin time (PT), activated partial thromboplastin time (APTT) and a high international normalized ratio (INR). Latamoxef was thought to be responsible for the coagulopathy in these patients, and coagulation disorder was relieved after vitamin-K intake. WHAT IS NEW AND CONCLUSION: We report on two cases of coagulopathy in patients given latamoxef. Advanced age, deficiency in vitamin-K intake, poor nutritional status, abnormal coagulation history, ongoing anti-coagulation/anti-aggregation therapy, renal dysfunction and polypharmacy are possible contributory factors, and should be looked out for when prescribing latamoxef.

Separation and characterization of unknown impurities in latamoxef sodium by LC-Q-TOF MS and a summary of their positive-ion fragmentation regularities.

A simple and sensitive method was developed for separation and characterization of seventeen impurities from commercial latamoxef sodium for injection by liquid chromatography combined with electrospray ionization and QTOF mass spectrometer (LC-ESI-QTOF MS). The chromatographic separation was performed on a Boston Green ODS-AQ C18 column (250 mm × 4.6 mm, 5 µm) under gradient mode using binary mobile phase: (A) ammonium acetate (10 mM)-methanol (99:1, v/v) and (B) ammonium acetate (10 mM)-methanol (70:30, v/v). Based on tandem multistage MS and high resolution MS data, the molecular formulas and structures of unknown impurities were inferred. A plausible formation mechanism of impurities was also proposed. In addition, the fragmentation regularity of degraded impurities in positive-ion mode was summarized.

Population pharmacokinetics and dosing optimization of latamoxef in neonates and young infants.

OBJECTIVES: There has been recent renewed interest in historical antibiotics because of the increased antibiotic-resistant bacterial strains. Latamoxef, a semi-synthetic oxacephem antibiotic developed in 1980s, has recently been brought back into use for treatment of infections in newborns; however, it is still used off-label in neonatal clinical practice due to the lack of an evidence-based dosing regimen. This study was performed to evaluate the pharmacokinetics of latamoxef in neonates and young infants, and to provide an evidence-based dosing regimen for newborns based on developmental pharmacokinetics-pharmacodynamics (PK-PD). METHODS: Opportunistic blood samples from newborns treated with latamoxef were collected to determine the latamoxef concentration by high-performance liquid chromatography with UV detection. Population PK-PD analysis was conducted using NONMEM and R software. A total of 165 plasma samples from 128 newborns (postmenstrual age range 28.4-46.1 weeks) were available for analysis. RESULTS: A two-compartment model with first-order elimination showed the best fit with the data. Current body weight, birth weight, and postnatal age were identified as significant covariates influencing latamoxef clearance. Simulation indicated that the current dosing regimen (30 mg/kg q12h) is adequate with an MIC of 1 mg/L. For an MIC of 4 mg/L, 30 mg/kg q8h was required to achieve a target rate of 70% of patients having a free antimicrobial drug concentration exceeding the MIC during 70% of the dosing interval. CONCLUSIONS: Based on the developmental PK-PD analysis of latamoxef, a rational dosing regimen of 30 mg/kg q12h or q8h was required in newborns, depending on the pathogen.

A microscale HPLC-UV method for the determination of latamoxef in plasma: An adapted method for therapeutic drug monitoring in neonates.

Latamoxef, a broad-spectrum anti-bacterial agent of the ß-lactam antibiotics, is used off-label in treatment of neonatal sepsis. Large inter-individual variability and uncertainty of treatment make therapeutic drug monitoring (TDM) useful to optimize antimicrobial therapy. The objective of this study was to develop and validate a simple, selective and reliable HPLC method for the determination of latamoxef in small volumes of plasma, which could be used in neonatal TDM. After a simple protein precipitation, analytes were separated with liquid chromatography and quantified by UV detection, with tinidazole as the internal standard. The calibration range was linear from 3.0 to 60.0 µg/mL. Intra- and inter-day precisions were < 7.2%. The acceptance criteria of accuracy (between 85 and 115%, 120% for lower limit of quantification) were met in all cases. A plasma volume of 50 µL was required to achieve the limit of quantification of 3.0 µg/mL. The TDM results showed a large variability in trough concentrations. A large number of patients were underdosed, highlighting the unmet need for TDM to optimize latamoxef therapy in neonates.

Effect and prognosis of treatment of lobar pneumonia with latamoxet / 中国生化药物杂志

Objective To investigate the therapeutic effect of cefradine on lobar pneumonia and its influence on the prognosis of patients with lobar pneumonia. Methods 90 cases of lobar pneumonia patients from December 2015 to May 2017 were randomly divided into the study group and the control group, with 45 cases in each group. The study group was treated with latamoxef on the basis of routine treatment, the control group was treated with cefoperazone on the basis of routine treatment ,recorded in two groups after 2 weeks of treatment. The clinical efficacy,drug related adverse reactions occur of the two groups were recorded after two weeks of treatment. Results The total effective rate in the study group(93.33%) was significantly higher than that of the control group(73.33%)(P<0.05). There was no significant difference in the incidence of drug-related adverse reactions between the two groups during the treatment period. Conclusion The application of latamoxet in the treatment of lobar pneumonia can significantly improve the clinical efficacy of patients, and is conducive to the protection of their prognosis and quality of life.

Effect and prognosis of treatment of lobar pneumonia with latamoxet / 中国生化药物杂志

Objective To investigate the therapeutic effect of cefradine on lobar pneumonia and its influence on the prognosis of patients with lobar pneumonia. Methods 90 cases of lobar pneumonia patients from December 2015 to May 2017 were randomly divided into the study group and the control group, with 45 cases in each group. The study group was treated with latamoxef on the basis of routine treatment, the control group was treated with cefoperazone on the basis of routine treatment ,recorded in two groups after 2 weeks of treatment. The clinical efficacy,drug related adverse reactions occur of the two groups were recorded after two weeks of treatment. Results The total effective rate in the study group(93.33%) was significantly higher than that of the control group(73.33%)(P<0.05). There was no significant difference in the incidence of drug-related adverse reactions between the two groups during the treatment period. Conclusion The application of latamoxet in the treatment of lobar pneumonia can significantly improve the clinical efficacy of patients, and is conducive to the protection of their prognosis and quality of life.

Clinical ineffectiveness of latamoxef for Stenotrophomonas maltophilia infection.

OBJECTIVES: Stenotrophomonas maltophilia shows wide-spectrum resistance to antimicrobials and causes various infections in immunocompromised or critically ill patients with high mortality. In this era of antibiotics resistance, a revival of old antibiotics is now featured. We examined the clinical usefulness of latamoxef (LMOX) for the treatment of S. maltophilia infection. PATIENTS AND METHODS: The observational study was retrospectively performed at Okayama University Hospital (Okayama, Japan) from January 2011 to December 2013. LMOX was administered to 12 patients with S. maltophilia infection, with eleven of those patients being admitted to the intensive care unit. RESULTS: Underlying conditions of the patients included postoperation, hematological transplantation, hepatic transplantation, and burn. Major infectious foci were surgical site infection (six cases), respiratory infection (four cases), blood stream infection (three cases), and burn site infection (one case). The doses of LMOX administered ranged from 1 g/d to 3 g/d for ten adult patients and from 40 mg/kg/d to 80 mg/kg/d for two pediatric patients. Microbiologic failure was seen in five (41.7%) of 12 cases, and 30-day and hospital mortality rates were 25% and 50%, respectively. Minimum inhibitory concentrations of LMOX were higher in the deceased group (4-64 µg/mL) than in the surviving group (1-4 µg/mL). CONCLUSION: LMOX treatment is not recommended for the treatment of S. maltophilia infection. Further investigation would be needed before its clinical use.

Determination of Impurities Including Polymers in Latamoxef Sodium by HPSEC / 中国药师

Objective:To establish a high performance size-exclusion chromatography ( HPSEC) method for the determination of impurities including polymers in latamoxef sodium. Methods:The analysis was performed on a Zenix SEC-150 column(7. 8 mm × 300 mm, 3 μm)with the mobile phase of 0. 005 mol·L-1 phosphate buffer solution [0. 005 mol·L-1 disodium hydrogen phosphate-0. 005 mol·L-1 sodium dihydrogen phosphate (61∶39), pH 7. 0] at a flow rate of 0. 8 ml·min-1. The detection wavelength was set at 254 nm. The column tempretrue was 25℃ and the injection volume was 10μl. Results:The impurities including polymers in latamoxef so-dium were completely separated from latamoxef. The linear range of latamoxef was 0. 98-97. 73 μg·ml-1(r=0. 999 9). The limit of quantitation of latamoxef was 2. 9 ng, and the detection limit was 1. 0 ng. The linear range of the total impurities was 0. 45-2. 8 mg· ml-1(r=0. 999 5). Conclusion: The established method is accurate, rapid and reproducible, and suitable for the determination of impurities including polymers in latamoxef sodium.

Compatible Stability of Ornidazole Sodium Chloride Injection with Latamoxef Disodium / 中国药房

OBJECTIVE:To study the compatible stability of ornidazole sodium chloride injection with latamoxef disodium.METHODS:Content changes of the mixed solution of ornidazole sodium chloride injection with latamoxef disodium were detected at different time by ultraviolet spectrophotometry;and the pH value,the appearance and the insoluble microparticles of the solution were also detected.RESULTS:Storing for 8 hours under room temperature,the combined solution looked clear,no significant change was noted regarding the content of ornidazole,but a slight reduction was noted regarding the content of lata_moxef disodium and the pH value had a slight change.CONCLUSION:Ornidazole sodium chloride injection and latamoxef dis_odium can be administered compatibly.