Case report: Decreased hemoglobin and multiple organ failure caused by ceftizoxime-induced immune hemolytic anemia in a Chinese patient with malignant rectal cancer.

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics. This study reports on a case of ceftizoxime-induced hemolysis observed in a patient in China. Case description: A Chinese patient diagnosed with malignant rectal cancer underwent antimicrobial therapy after laparoscopic partial recto-sigmoid resection (L-Dixon). After receiving four doses of ceftizoxime, the patient developed symptoms including rash, itchy skin, and chest distress, followed by a rapid decline in hemoglobin levels, the presence of hemoglobin in the urine (hemoglobinuria), renal failure, and disseminated intravascular coagulation. Laboratory analysis revealed high-titer antibodies against ceftizoxime and red blood cells (RBCs) in the patient's serum, including immunoglobulin M (IgM) (1:128) antibodies and immunoglobulin G (IgG) (1:8) antibodies, with noted crossreactivity to ceftriaxone. Significant improvement in the patient's hemolytic symptoms was observed following immediate discontinuation of the drug, two plasma exchanges, and extensive RBC transfusion. Conclusion: This case, together with previous reports, underscores the importance of considering DIIHA in patients who exhibit unexplained decreases in hemoglobin levels following antibiotic therapy. A thorough examination of the patient's medical history can provide crucial insights for diagnosing DIIHA. The effective management of DIIHA includes immediate cessation of the implicated drug, plasma exchange, and transfusion support based on the identification of specific drug-dependent antibodies through serological testing.

FDA-Approved Oximes and Their Significance in Medicinal Chemistry.

Despite the scientific advancements, organophosphate (OP) poisoning continues to be a major threat to humans, accounting for nearly one million poisoning cases every year leading to at least 20,000 deaths worldwide. Oximes represent the most important class in medicinal chemistry, renowned for their widespread applications as OP antidotes, drugs and intermediates for the synthesis of several pharmacological derivatives. Common oxime based reactivators or nerve antidotes include pralidoxime, obidoxime, HI-6, trimedoxime and methoxime, among which pralidoxime is the only FDA-approved drug. Cephalosporins are ß-lactam based antibiotics and serve as widely acclaimed tools in fighting bacterial infections. Oxime based cephalosporins have emerged as an important class of drugs with improved efficacy and a broad spectrum of anti-microbial activity against Gram-positive and Gram-negative pathogens. Among the several oxime based derivatives, cefuroxime, ceftizoxime, cefpodoxime and cefmenoxime are the FDA approved oxime-based antibiotics. Given the pharmacological significance of oximes, in the present paper, we put together all the FDA-approved oximes and discuss their mechanism of action, pharmacokinetics and synthesis.

Eggerthella lenta bacteremia successfully treated with ceftizoxime: case report and review of the literature.

Eggerthella lenta is a normal human microflora that is anaerobic, non-sporulating, and Gram positive. However, an increasing number of studies have shown that it could also be an important pathogen for humans, even causing life-threatening infection under certain conditions. However, understanding its pathogenic mechanism and treatment options still need to be improved; more clinical data are needed to explore it further. In this article, we report a case of ceftizoxime-cured E. lenta bacteremia and review the recent literature to provide more clinical data for the diagnosis of E. lenta bacteremia. Our report suggests that the frequency of E. lenta bacteremia is increased in patients with hematologic or solid organ cancer, diabetes mellitus and also in those with appendicitis.

Pharmacokinetics and Efficacy of Ceftriaxone in Staphylococcal Mastitis in Crossbred Cows Following Single Intravenous Administration.

BACKGROUND: Clinical mastitis is an important production disease of dairy animals, causing significant economic losses. OBJECTIVE: Disposition kinetics of ceftriaxone was conducted in healthy lactating and staphylococcal mastitic crossbred cows in field condition following single-dose intravenous administration of only ceftriaxone. METHODS: A single dose of ceftriaxone at 20 mg kg-1 body weight was administered intravenously through jugular vein to six clinically healthy and six mastitic crossbred cows after proper diagnosis and three mastitic cows remained untreated (positive control). Blood and milk samples were collected at 0 (pre-dosing), 5, 15, 30 min, and 1, 24, 48, 72, 96 and 120 h post drug administration and analyzed for ceftriaxone and its active metabolite (ceftizoxime) by high-performance liquid chromatography. RESULTS: Ceftriaxone achieved a peak mean plasma concentration of 131.67±1.83 µg mL-1 at 5 min, which decreased sharply until 1 h (35.56±0.44 µg mL-1) and was below detection limit at 24 h post drug administration in mastitic crossbred cows. On the other hand, ceftizoxime (active metabolite of ceftriaxone) achieved a peak level of 55.42±3.34 µg mL-1 at 72 h and could not be detected at 120 h post drug administration in the milk of those mastitic crossbred cows. The Staphylococcus aureus colony count in mastitic crossbred cows was 49.33±6.55 × 105 c.f.u./mL and the lowest colony count was achieved at 72 h with no colony at 120 h post drug administration. All the staphylococcal mastitis affected crossbred cows were cured on day 5. CONCLUSION: Ceftriaxone may prove to be effective in the treatment of staphylococcal mastitis in crossbred cows following single-dose intravenous administration at 20 mg kg-1 body weight.

Computational design of new enzymes for hydrolysis and synthesis of third-generation cephalosporin antibiotics.

Engineering active sites in inert scaffolds to catalyze chemical transformations with unnatural substrates is still a great challenge for enzyme catalysis. In this research, a p-nitrobenzyl esterase from Bacillus subtilis was identified from the structural database, and a double mutant E115A/E188A was designed to afford catalytic activities toward the hydrolysis of ceftizoxime. A quadruple mutant E115A/E188A/L362S/I270A with enhanced catalytic efficiency was created to catalyze the condensation reaction of ethyl-2-methoxy-amino-2-(2-aminothiazole-4-yl) acetate with 7-amino-3-nor-cephalosporanic acid to produce ceftizoxime in a fully aqueous medium. The catalytic efficiencies of the computationally designed mutants E115A/E188A/L362S/I270A and E115A/Y118 K/E188 V/I270A/L362S can be taken as starting points to further improve their properties towards the practical application in designing more ecology-friendly production of third-generation cephalosporins.

Fabrication and Characterization of Ceftizoxime-Loaded Pectin Nanocarriers.

Ceftizoxime (C13H12N5NaO5S2)is a parenteral, third-generationcephalosporin antibiotic used to treat bacterial infections including ear, nose, and throat infections. In this work, pectin has been used as a nanocarrier for ceftizoxime due to its high biocompatibility and non-toxicity with tunable surface properties. Ceftizoxime-loaded pectin nanocarriers (CPN) were successfully synthesized by the solvent displacement method. Optimization of nanoformulation was done by response surface methodology using Design-Expert software. The optimized formulation examined various in-vitro characterizations such as particle size, morphology, and FTIR studies. TEM results revealed irregular shape nanoparticles within the range of 29-110 nm. The in-vitro drug release using the dialysis method was performed after 24h where nanoformulation showed sustained drug release. Drug-loaded nanoparticles revealed good antimicrobial activity against Bacillus cereus, Bacilluspolymyxa, Enterobacteraerogenes, andPseudomonasaeruginosa.

Marked reduction in haemoglobin levels secondary to ceftizoxime-induced immune haemolytic anaemia in diabetic patients.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced immune haemolytic anaemia (DIIHA) is rare and difficult to diagnose. In diabetic patients, the diagnosis of DIIHA is even harder. In the current study, we report on two cases of ceftizoxime-induced immune haemolytic anaemia in diabetic patients. CASE DESCRIPTION: Two diabetic patients (suffering from type 1 and type 2 diabetes mellitus, respectively) presented with rapid reduction in haemoglobin levels when exposed to ceftizoxime (2g q12h). They both achieved symptom improvement after switching to another antibiotic. WHAT IS NEW AND CONCLUSION: The persistently reduced haemoglobin levels in diabetic patients may contribute to DIIHA. Reviewing patients' medical records might provide some valuable clues as to the causes of DIIHA.

Disposition of ceftizoxime in Staphylococcal mastitis in Indian crossbred cows.

Disposition of ceftizoxime was studied in Indian crossbred cows following a single IV dosing in field conditions. Six healthy lactating and six mastitic crossbred cows were assigned to two groups (Group 1 and Group 2). A single IV administration of ceftizoxime at the dose rate of 20mg/kg was administered to cows in both groups. Peak concentrations were recorded at 5min, decreasing sharply until 1h with plasma concentrations of 46.38±0.30µg/mL; concentrations were below detection limits at 24h. Ceftizoxime achieved peak concentrations at 96h and persisted up to 120h at a concentration of 36.71±0.96µg/mL in the milk of mastitic Indian crossbred cows. Staphylococcal colony count in acute mastitis was 52.33±4.98×105 colony forming units/mL milk and no growth was detected at 96h post-dosing, indicating that ceftizoxime following single IV administration at 20mg/kg may be effective to treat acute staphylococcal mastitis.

99m Tc-Ceftizoxime: Synthesis, characterization and its use in diagnosis of diabetic foot osteomyelitis.

INTRODUCTION: The diagnosis of diabetic foot osteomyelitis is crucial and challenging for the proper management of diabetic foot. 99m Tc labelled Ceftizoxime was used as a non-invasive diagnostic agent for diabetic foot osteomyelitis. METHODS: Ceftizoxime [CFT], a third generation cephalosporin, was used in a simple and direct method for the synthesis of 99m TcO4 - labelled infection imaging agent with stannous chloride as reducing agent. Its radiochemical purity was checked by thin Layer chromatography. Partition co-efficient was measured with phosphate buffer and chloroform. The radiochemical complex was injected to control and infected animal model for 3 hours in-vivo localization studied with the help of dual head gamma camera. The labelled complexes were injected to 5 patients of known type II diabetes mellitus suspected of diabetic foot osteomyelitis. All patients underwent dynamic and static 99m Tc-MDP and 99m Tc-CFT scans. RESULTS: The synthesized radio labelled complex was 98.8% pure, with hydrophilic character. When injected to animal model, at 120 minutes, 49.3% was localized in foci of infection with 3.35% in liver and excretion through kidney. Human studies were interpreted as true or false positive and true or false negative based on bone histopathology/culture and clinical follow-up. We found that of 5 patients, 2 were true positive, 2 as true negative with no false positive or negative and 01 patient had soft tissue infection. CONCLUSION: This study showed that 99m Tc-CFT labelled complex could be used for detection of diabetic foot osteomyelitis; however, further confirmation of results with a larger patient population would be optimal.

Effect of combination therapy with ceftizoxime and clotrimazole in the treatment of otomycosis.

BACKGROUND AND PURPOSE: There are controversial findings regarding the efficacy of antifungal drugs in the treatment of a ruptured eardrum following fungal infections. Regarding this, the aim of the present study was to evaluate the therapeutic effect of the co-administration of antifungal and antibacterial agents in the treatment of otomycosis with tympanic membrane perforation. MATERIALS AND METHODS: This analytical, clinical trial was conducted on 87 patients with otomycosis showing no bacterial elements in the direct observation and culture. The study population was assigned into two groups of intervention (n=45) and control (n=42). The demographic and clinical data, as well as the data related to the direct observation and culture of the ear samples were recorded in a checklist. All statistical analysis was performed in SPSS (version 24). RESULTS: The most prevalent symptoms in both groups were hearing loss and itching, and the most common finding was secretion. Aspergillus and Candida were the most frequent fungi isolated from the samples. After the implementation of combination therapy, the intervention group demonstrated a significant decrease in symptoms and signs, compared to the control group (P=0.005). CONCLUSION: The findings of the present study indicated that the use combination therapy with ceftizoxime powder and clotrimazole ointment was effective the in treatment of the patients with tympanic membrane rupture showing no bacterial effects in direct examination and culture.

Pharmaceutical analysis of different antibiotic regimens in the treatment of lower respiratory tract infection.

The present study aimed to discuss and compare the effects and expenses of different antibiotic regimens in the treatment of lower respiratory tract infection (LRTI). A retrospective analysis was performed on 200 patients diagnosed with LRTI and treated at the Department of Respiratory Medicine of Dongying People's Hospital from February 2015 to May 2017. The patients were randomly divided into Group A, Group B, Group C and Group D, with 50 cases in each group, and were treated with ceftriaxone sodium, ceftizoxime sodium, levofloxacin and azithromycin, respectively. Venous blood of patients was collected. White blood cells (WBC) of venous blood were detected using a hematology analyzer and C-reactive protein (CRP) was tested with latex immunoturbidimetry. Moreover, therapeutic effects and drug costs of four different antibiotics were compared. No adverse reactions occurred to patients in the four groups during the treatment process. The value at each time point after treatment was significantly decreased compared with that at the previous time point before treatment within the group (P<0.01). The treatment expenses of patients in Group A, Group B and Group D were significantly increased compared with those in Group C (P<0.01), the treatment expenses of patients in Group B and Group D were significantly increased compared with those in Group A (P<0.01) and the treatment expenses of patients in Group D were significantly increased compared with those in Group B (P<0.01). Ceftriaxone sodium, ceftizoxime sodium, levofloxacin and azithromycin all have a good antimicrobial efficacy. The treatment condition of LRTI can be dynamically monitored by WBC and CRP which can accurately reflect the progression condition of patients' illness and the treatment effect. In economic terms, the treatment cost of levofloxacin is the lowest; thus, it is worthy of clinical popularization and application.

The urinary excretion of metformin, ceftizoxime and ofloxacin in high serum creatinine rats: Can creatinine predict renal tubular elimination?

The renal excretion of creatinine and most drugs are the net result of glomerular filtration and tubular secretion, and their tubular secretions are mediated by individual transporters. Thus, we hypothesized that the increase of serum creatinine (SCr) levels attributing to inhibiting tubular transporters but not glomerular filtration rate (GFR) could be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine. In this work, we firstly developed the creatinine excretion inhibition model with normal GFR by competitively inhibiting tubular transporters, and investigated the renal excretion of metformin, ceftizoxime and ofloxacin in vivo and in vitro. The results showed that the 24-hour urinary excretion of metformin and ceftizoxime in model rats were decreased by 25% and 17% compared to that in control rats, respectively. The uptake amount and urinary excretion of metformin and ceftizoxime could be inhibited by creatinine in renal cortical slices and isolated kidney perfusion. However, the urinary excretion of ofloxacin was not affected by high SCr. These results showed that the inhibition of tubular creatinine transporters by high SCr resulted to the decrease of urinary excretion of metformin and ceftizoxime, but not ofloxacin, which implied that the increase of SCr could also be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine in normal GFR rats.

Ceftizoxime-induced immune hemolytic anemia associated with multi-organ failure / 영남의대학술지

Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure — shortly after the infusion of ceftizoxime — the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.

Ceftizoxime-induced immune hemolytic anemia associated with multi-organ failure / 영남의대학술지

Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure — shortly after the infusion of ceftizoxime — the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.

Literature Analysis of Ceftizoxime-induced Hemolytic Anemia / 中国药房

OBJECTIVE:To provide reference for clinical prevention and treatment of ceftizoxime-induced hemolytic anemia by investigating the situation of ceftizoxime-induced hemolytic anemia. METHODS:Using Chinese and English“ceftizoxime”“he-molysis”and other words as key words,related literatures during 1986-2015 were retrieved from CNKI,Wanfang database and PubMed database. Those literatures were analyzed statistically in respects of general information,clinical drug use and manifesta-tion,occurrence time and outcome,etc. The mechanisms of hemolytic anemia were analyzed to put forward prevention and treat-ment measures. RESULTS & CONCLUSIONS:A total of 11 literatures were retrieved,including 4 foreign literatures and 7 domes-tic ones. There were 15 cases in total,including 5 foreign cases and 10 domestic cases. According to the patient’s age,there were 7 cases of infants,4 cases of the elderly,3 cases of middle-aged people and 1 case of youth. The hemolytic anemia often occurred on the 2-7 day(8 cases). Most of the patients were improved after treatment,but there were 3 patients who died. The mechanism of hemolytic anemia mainly included the production of immune complex and non-immunologic protein adsorption. It is suggested to investigate allergic reaction history,pay attention to sensitization test on skin,select suitable drug dosage and avoid drug combina-tion. The patient’s medications should be monitored closely. Once hemolytic anemia occurs,it should be immediately stop using the drug and take appropriate measures as hormone treatment,comprehensive treatment,blood transfusion treatment,to avoid en-dangering the life safety of patients.

Human serum paraoxonase-1 (hPON1): in vitro inhibition effects of moxifloxacin hydrochloride, levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium.

In this study, we investigated the effects of antibacterial drugs (moxifloxacin hydrochloride, levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium) on human serum paraoxonase-1 (hPON1) enzyme activity from human serum in vitro conditions. For this purpose, hPON1 enzyme was purified from human serum using simple chromatographic methods. The antibacterial drugs exhibited inhibitory effects on hPON1 at low concentrations. Ki constants were calculated to be 2.641 ± 0.040 mM, 5.525 ± 0.817 mM, 35.092 ± 1.093 mM, 252.762 ± 5.749 mM and 499.244 ± 10.149 mM, respectively. The inhibition mechanism of moxifloxacin hydrochloride was competitive, whereas levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium were noncompetitive inhibitors.

Levofloxacin lactate and ceftizoxime for anti-infective therapy of acute edematous biliary pancreatitis: A comparison of efficacy / 第二军医大学学报

Objective To compare the anti-infective effects of levofloxacin lactate and ceftizoxime in treatment of acute edema biliary pancreatitis, so as to provide reference for clinical anti-infective therapy of acute pancreatitis. Methods A total of 180 consecutive patients with acute edema biliary pancreatitis, who were treated in the emergency department of Changhai Hospital from January 2014 to November 2014, were selected in the present study, and they were randomly divided into levofloxacin lactate treatment group and ceftizoxime treatment group. In addition to conventional treatment including water fasting, gastrointestinal decompression, acid suppression, enzyme suppression and nutrition support, etc., levofloxacin lactate therapy and ceftizoxime were given separately to control the infection in the two groups. Then the following parameters were observed: remission of vomiting, abdominal pain and bloating, open eating time, hospital stays, blood routine and biochemistry test, C reaction protein (CRP), serum amylase, and the absorption of inflammation of the pancreas in imaging. Results The levofloxacin lactate treatment group had a significantly higher effective rate than the ceftizoxime treatment group (P <0.05). Compared with the ceftizoxime treatment group, the remission of vomiting and abdominal pain and bloating was significantly faster in the levofloxacin lactate treatment group (P <0.01); the open eating time, hospital stays hemogram and blood amylase recovery were also significantly improved in the levofloxacin lactate treatment group (P <0.05); and the absorption of inflammation of the pancreas in CT imaging was significantly faster (P <0.05). Conclusion The study shows that levofloxacin lactate is more effective than ceftizoxime in the anti-infective therapy of acute edema biliary pancreatitis.

Impurity profile study of ceftizoxime sodium for injection / 中国药学杂志

OBJECTIVE: To investigate the impurity profile of ceftizoxime sodium for injection and develop the impurity control strategy.

A Case of Immune Hemolytic Anemia Induced by Ceftizoxime and Cefobactam (Sulbactam/Cefoperazone) / 대한진단검사의학회지

Simultaneous drug-induced immune hemolytic anemia (DIIHA) caused by multiple drugs is rare. We report a case of a patient who developed DIIHA caused by 2 drugs. The patient's serum exhibited agglutination of ceftizoxime- or sulbactam-coated red blood cells (RBCs; via a drug-adsorption mechanism) and of uncoated RBCs in the presence of sulbactam (via an immune-complex mechanism). Although ceftizoxime is known to exhibit a positive reaction by an immune-complex method with or without reactivity with drug-coated RBCs, this patient's antibodies were reactive only against drug-coated RBCs. On the other hand, sulbactam, which is known to cause hemolytic anemia by nonimmunologic protein adsorption, exhibited positive reactions in tests with both drug-coated RBCs and in the presence of sulbactam. This is the first report of DIIHA due to a sulbactam-cefoperazone combination and the fourth report of DIIHA due to ceftizoxime. Owing to the patient's complicated laboratory results, DIIHA was suspected only at a late stage. We propose that for the prompt diagnosis of DIIHA, tests for all possible causative drugs should be conducted by 2 methods.

Production Technology of Ceftizoxime Sodium / 中国药房

OBJECTIVE:To study the production process of ceftizoxime sodium.METHODS:Ceftizoxime acid was prepared with 7-Amino-3-norcephem-4-carboxylic acid(7-ANCA)and AE-ester ceftizoxime acid as raw material;then ceftizoxime sodium was obtained through the reaction between ceftizoxime acid and sodium carbonate.The effects of parameters including reaction time,and amount and dripping velocity of ethanol,the amount of sodium carbonate,and pH of solution on quality of product were studied.RESULTS:The reaction process could be realized successfully.The optimal parameters for the synthesis of ceftizoxime sodium were as follows:reaction time=1.5h,the velocity of dripping ethanol=400mL? h-1,reaction temperature