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.

Clinical Trial to Reconfirm the Efficacy and Safety of Cefetamet Pivoxil Treatment in Sinusitis Patients: A Double-Blind, Randomized, Parallel Designed, Multicenter, Active Comparator Study (CASIS Study).

OBJECTIVE: To evaluate the clinical efficacy and safety of cefetamet pivoxil for the treatment of acute bacterial rhinosinusitis in Korean patients compared to treatment with cefdinir. METHODS: A prospective, multicenter, randomized double-blind, comparative study was conducted by the Departments of Otorhinolaryngology-Head and Neck Surgery at 17 hospitals or universities in the Republic of Korea from March 2017 to April 2019. A total of 309 patients were screened and 249 patients participated in the study. RESULTS: Treatment with cefetamet pivoxil for 2 weeks showed 82.4% clinical cure and improvement rates in patients with acute bacterial rhinosinusitis compared to 84.68% in those taking cefdinir for 2 weeks, showing that cefetamet pivoxil administered twice a day for 2 weeks was as effective as cefdinir 3 times a day for 2 weeks for the treatment of acute bacterial rhinosinusitis. The overall adverse reaction rates of both drugs were 10.56% in the cefetamet pivoxil group and 15.49% in the cefdinir group, without serious adverse events or drug reactions. CONCLUSIONS: Cefetamet pivoxil twice a day was as efficacious and safe as cefdinir 3 times a day for the treatment of acute bacterial rhinosinusitis, which suggested that cefetamet pivoxil may be a suitable alternative to cefdinir.

Clostridium difficile infection after antibiotic use.

Every day, patients are prescribed antibiotics to treat infections, and some of these patients will subsequently develop a superinfection with Clostridium difficile. Although the use of antibiotics is a necessary part of modern medical care, clinicians must be judicious with their use and choice of antibiotics to prevent consequences for patients whenever possible.

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.

[Phase I clinical trial on the safety of injectable cefetamet sodium with a single dose in healthy volunteers].

OBJECTIVE: To investigate the safety and maximum tolerable dosage of injectable cefetamet sodium Sixty healthy volunteers were enrolled in this study. with a single infusion in Chinese healthy volunteers. METHODS: A double-blinded, randomized, placebo-controlled design was adopted. Eight dosages ranging from 100 mg to 5 000 mg were tested. The pharmacokinetics of the drug was analyzed using a Latin square three-cross self-controlled design, with 12 healthy volunteers receiving 500 mg, 1 000 mg and 2 000 mg of injectable cefetamet sodium in a randomized sequence. Blood and urine samples were collected and analyzed using high performance liquid chromatography with UV detection. The main pharmacokinetics parameters were calculated with DAS2.0 software. RESULTS: 59 healthy volunteers completed the tolerance tests. Clinical adverse reactions occurred in 22.73% of participants in the test group and 6.67% of participants in the placebo group; but the difference was not statistically significant. Common adverse events included infusion pain and dizziness. Rare adverse events such as palpitations, diarrhea and rash occurred in participants in the test group. All of the adverse reactions were mild. Abnormal laboratory test results occurred in 43.18% participants in the test group and 53.33% participants in the placebo group; again the difference was not statistically significant. Common abnormal laboratory test results included abnormal bowel flora, stool abnormalities, abnormal urine and elevated serum potassium. After a single infusion of 500 mg, 1 000 mg and 2 000 mg of injectable cefetamet sodium, peak concentration of the drug at 0.5 h reached (37.92 +/- 7.43), (74.90 +/- 10.67) and (148.54 +/- 31.63) mg/L, with areas under concentration-time curve of (72.08 +/- 14.98), (144.28 +/- 24.57) and (286.66 +/- 54.25) (mg x h)/L, respectively. Their elimination half-life was (2.03 +/- 0.38), (2.04 +/- 0.26), and (2.12 +/- 0.26) h, respectively. The disposition of cefetamet was presented as a two-compartment model with linear kinetics. The 24-hour urinary accumulation excretion was 76.6%-67.5%. CONCLUSION: The maximum single tolerated dose of injectable cefetamet sodium is 5 000 mg. The pharmacokinetics is a two-compartment model with linear kinetics within a dose range 500-2 000 mg.

Cefpodoxime proxetil-related hemolysis and acute interstitial nephritis.

OBJECTIVE: We report a case of acute interstitial nephritis (AIN) and immune hemolytic anemia (IHA) associated with cefpodoxime therapy. CASE SUMMARY: A patient with a recent history of cefpodoxime proxetil treatment presented with elevated serum creatinine, oliguria, nausea, vomiting, and dyspnea. Evidence of renal failure, abnormal urinalysis, and renal biopsy with inflammatory infiltrate in the interstitium confirmed a diagnosis of AIN. The patient subsequently developed IHA, which was confirmed by peripheral blood smear results and positive Coombs' test. The patient recovered after dialysis therapy and 2 days of intravenous methylprednisolone (500mg/day) followed by oral prednisolone (60 mg/day), which was rapidly tapered and stopped within 3 weeks. CONCLUSIONS: To our knowledge, cefpodoxime-induced AIN and IHA are unprecedented. Physicians should be aware that drug-induced AIN and hemolysis can be associated with cefpodoxime proxetil.

Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: a randomized trial.

CONTEXT: Although fluoroquinolones remain the most reliable urinary antimicrobial, resistance rates have increased and effective fluoroquinolone-sparing antimicrobials are needed. OBJECTIVE: To determine whether cefpodoxime is noninferior to ciprofloxacin for treatment of acute cystitis. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind trial of 300 women aged 18 to 55 years with acute uncomplicated cystitis comparing ciprofloxacin (n = 150) with cefpodoxime (n = 150); patients were from a student health center in Seattle, Washington, and a referral center in Miami, Florida. The study was conducted from 2005 to 2009 and outcomes were assessed at 5 to 9 days and 28 to 30 days after completion of therapy. Intent-to-treat and per-protocol analyses were performed; 15 women in the ciprofloxacin group and 17 women in the cefpodoxime group were lost to follow-up. INTERVENTIONS: Patients were given 250 mg of ciprofloxacin orally twice daily for 3 days or 100 mg of cefpodoxime proxetil orally twice daily for 3 days. MAIN OUTCOME MEASURES: Overall clinical cure (defined as not requiring antimicrobial treatment during follow-up) at the 30-day follow-up visit. Secondary outcomes were clinical and microbiological cure at the first follow-up visit and vaginal Escherichia coli colonization at each follow-up visit. The hypothesis that cefpodoxime would be noninferior to ciprofloxacin by a 10% margin (ie, for the difference in the primary outcome for ciprofloxacin minus cefpodoxime, the upper limit of the confidence interval would be <10%) was formulated prior to data collection. RESULTS: The overall clinical cure rate at the 30-day visit with the intent-to-treat approach in which patients lost to follow-up were considered as having clinical cure was 93% (139/150) for ciprofloxacin compared with 82% (123/150) for cefpodoxime (difference of 11%; 95% CI, 3%-18%); and for the intent-to-treat approach in which patients lost to follow-up were considered as having not responded to treatment, the clinical cure rate was 83% (124/150) for ciprofloxacin compared with 71% (106/150) for cefpodoxime (difference of 12%; 95% CI, 3%-21%). The microbiological cure rate was 96% (123/128) for ciprofloxacin compared with 81% (104/129) for cefpodoxime (difference of 15%; 95% CI, 8%-23%). At first follow-up, 16% of women in the ciprofloxacin group compared with 40% of women in the cefpodoxime group had vaginal E coli colonization. CONCLUSIONS: Among women with uncomplicated cystitis, a 3-day regimen of cefpodoxime compared with ciprofloxacin did not meet criteria for noninferiority for achieving clinical cure. These findings, along with concerns about possible adverse ecological effects associated with other broad-spectrum ß-lactams, do not support the use of cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00194532.

A multicentric, open label, randomised, postmarketing efficacy study comparing multidose of lincomycin hydrochloride capsule 500 mg with multidose cefpodoxime proxetil tablet 200 mg in patients with tonsillitis, sinusitis.

Tonsillitis causes considerable short and medium term morbidity, and can be recurrent. Sinusitis can be acute (less than 4 weeks), subacute (4-8 weeks) or chronic (8 weeks or more). To study the comparative efficacy and safety of multidose treatments of lincomycin hydrochloride 500 mg capsules against cefpodoxime proxetil 200 mg tablets on its outcome in the Indian scenario are the aims and objective of the study. A total of 41 tonsillitis, sinusitis cases of either gender aged above 18 years were enrolled in the study. The diagnosis of sonsillitis, sinusitis was made based on examination of symptoms and throat swab. A randomised treatment of either lincomycin hydrochloride 500 mg capsules or cefpodoxime proxetil 200 mg tablets twice daily for five days alongwith other concomitant medications depending on related symptoms was given to 40 patients. At the end of study, all patients were re-evaluated and the response rate was assessed. The most common clinical symptoms were body temperature, headache, throat pain, postnasal discharge, mucopus, odynophagia, sinus tenderness, nasal congestion, pharyngeal congestion and tonsillar congestion. The overall response rate of lincomycin hydrochloride in all the symptoms except headache was more effective than cefpodoxime proxetil. Out of 100% (n = 20) patients in each group, 67.89% in lincomycin and 52.27% in cefpodoxime patients achieved complete relief, in all the clinical symptoms. The study suggests that lincomycin hydrochloride capsules, a conventional antibiotic indicates effective treatment for relief from tonsillitis and sinusitis, as compared to new third generation antibiotic.

A case of immune hemolytic anemia induced by ceftizoxime and cefobactam (sulbactam/cefoperazone).

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.

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.

Aminopenicillin-induced exanthema allows treatment with certain cephalosporins or phenoxymethyl penicillin.

OBJECTIVES: Aminopenicillin-induced exanthema poses a problem in the management of infectious diseases. Due to theoretically possible immunological cross-reactivity, all beta-lactam drugs, i.e. penicillins, penicillin derivatives and cephalosporins, are usually avoided. The available alternative antibiotics (macrolides, quinolones and glycopeptides) may be less effective, have more side effects, and their use increases medical costs. Moreover, their use contributes to the increasing bacterial resistance to antibiotics. The aim of the study is to demonstrate that patients with aminopenicillin-induced exanthema may receive specific beta-lactams for future antibiotic therapy. METHODS: Skin testing followed by oral challenges to identify beta-lactams that are tolerated by patients despite confirmed delayed-type non-immunoglobulin E (IgE)-mediated allergic hypersensitivity to aminopenicillins. RESULTS: Sixty-nine out of 71 patients (97.2%) with non-IgE-mediated allergic hypersensitivity to aminopenicillins tolerate cephalosporins without an aminobenzyl side chain such as cefpodoxime or cefixime and 51 patients (71.8%) also tolerate phenoxymethyl penicillin. CONCLUSIONS: The majority of patients with non-IgE-mediated allergic hypersensitivity to aminopenicillins do not cross-react to certain cephalosporins or phenoxymethyl penicillin. Skin and drug challenge tests can be helpful to determine individual cross-reactivity.

Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release.

Cefoselis is a widely used beta-lactam antibiotic, but occasionally induces seizures and convulsion in elder and renal failure patients. However, beta-lactams are known not to pass through the blood-brain barrier (BBB). In this study, we examined the BBB penetration of cefoselis in normal and renal failure rats by means of brain microdialysis. Cefoselis was dose-dependently appeared in brain extracellular fluid in proportion to its blood level. The elimination constant from brain extracellular fluid (apparent) was slightly lower than that from blood. These results indicated that cefoselis might penetrate the BBB or be discharged by a certain transport system. In contrast to the result of cefoselis, cefazolin, a leading drug of cephalosporins, could not be detected in the brain extracellular fluid after an intravenous injection. In renal dysfunction rats, the elimination half-lives of cefoselis from both blood and brain were extensively prolonged. This would be one of responsible factors inducing seizures seen in patients. However, the additional factor, such as decrease in brain function related to aging, would be involved in seizures in patient received cefoselis, because an extremely high dose was required to induce seizures even in renal failure rats. A local administration of cefoselis into the hippocampus through the microdialysis probe caused a striking elevation of extracellular glutamate, with a minimum increase in gamma-aminobutyric acid (GABA). However, a systematic cefoselis administration via the tail vein did not elevate extracellular glutamate and GABA concentrations in the hippocampus of renal failure rats that exhibited marked seizures. These results suggested that not the stimulation of glutamate release, but the blockade of GABA receptors might be responsible for the seizure induced by cefoselis.

Comparative evaluation of cefpodoxime versus cefixime in children with lower respiratory tract infections.

OBJECTIVE: The emergence of penicillin and macrolide resistant strains, responsible for Acute Lower Respiratory Tract Infections in children has offered third generation cephalosporins the platform to perform. The aim of the present study was to evaluate two third generation oral cephalosporins for their empirical use in community acquired lower respiratory tract infections in pediatric patients. An assessment of the clinical cure and bacteriological eradication rates and an overall tolerability was made. METHODS: It was a prospective, open, comparative, multicentric study. 776 children (Mean age 10 years) with LRTIs were included and randomly allotted to two groups respectively. A total of 396 children were given cefpodoxime susp 5 mg/kg b.i.d. and 380 patients on cefixime 4 mg/kg b.i.d. for 10-14 days. RESULTS: At the end of therapy, the clinical success with cefpodoxime was 97% as against 86.8% with cefixime. Bacterial eradication was 93.4% with cefpodoxime and 82.9% with cefixime. CONCLUSION: Cefpodoxime has been found to be a well-tolerated and superior alternative to cefixime synergistically documenting the extended spectrum of activity.

[Treatment of functional signs of acute maxillary rhinosinusitis in adults. Efficacy and tolerance of administration of oral prednisone for 3 days]. / Traitement des signes fonctionnels des rhinosinusites maxillaires aiguës de l'adulte. Efficacité et tolérance de la prednisone administrée par voie orale pendant 3 jours.

OBJECTIVE: Acute maxillary rhinosinusitis (AMRS) is a pathology in which the pain is often severe and requires appropriate treatment. Although the use of antibiotics is widely documented, the interest of short cycles of corticosteroids in the treatment of the functional manifestations of AMRS is based on professional experience. The aim of this study was to assess the efficacy and tolerance to prednisone administered for 3 days in addition to antibiotherapy in patients presenting with an AMRS. METHOD: This was a double blind, randomised study in parallel groups and controlled versus a placebo, involving patients aged over 18, presenting with an AMRS confirmed by X-ray and endoscopy, having developed less than 5 days and complaining of spontaneous pain assessed as >or=50 millimetres on a visual analog scale (VAS). Together with cefpodoxime, the patients received either prednisone (0.8 to 1.2 mg/kg) for 3 days or a placebo. The primary efficacy endpoint was the mean of the differences versus the baseline value of pain (MPID - mean pain intensity difference) assessed on the VAS from Day 1 to Day 3. The secondary endpoints assessed were the mean of the differences in intensity of nasal obstruction, assessed in the same way as the MPID, the time lapse before the orally expressed relief of the pain (PRID - pain reflief intensity difference) and the administration of paracetamol during the first 3 days. RESULTS: 289 patients (placebo 147, prednisone 142) were assessable for analysis in intent-to-treat (ITT). The global spontaneous pain on inclusion, measured by a VAS was of 73.0 +/- 14.1 mm. The assessments made during the first 3 days of treatment showed a statistically significant difference in favour of the prednisone group regarding MPID: - 4.82 mm (CI 95% -9.25; -0.40) (p=0.03), nasal obstruction - 5.0 mm (CI 95% -9.1; -0.8) (p=0.02) and consumption of paracetamol (p=0.03). There was no difference between the two groups after the end of the antibiotherapy. The tolerance measured throughout the study was comparable between the two groups. CONCLUSION: This study clearly showed the efficacy of a short course of oral prednisone (3 days), versus a placebo, in the treatment of the functional signs of acute maxillary rhinosinusitis with severe pain in adults in addition to an appropriate antibiotic treatment.

Cefpodoxime: pharmacokinetics and therapeutic uses.

Cefpodoxime is a semi-synthetic, third generation cephalosporin. The drug is available for use as a prodrug-Cefpodoxime proxetil, which is absorbed readily from the gut. It reaches adequate levels exceeding the MIC in most of the body fluids. It is excreted by kidneys, unchanged. Dose needs adjustment in compromised renal function. The drug is active against common gram-positive cocci like staphylococci including penicillinase producing strains, streptococci and gram negative bacteria like Hemophilus, E. coli, Klebsiella, Moraxella, Meningococci, Gonococci etc. The drug is useful in common upper and lower respiratory tract infections, sinusitis, and otitis media. The drug is also used in skin and soft tissue infections, urinary tract infection and respiratory tract infection. Cefpodoxime is being used as a step down from parenteral cephalosporin. The recommended dose is 8-10 mg/kg/d in a single or two doses. Different schedules have been given for different infections. The drug is safe, effective as a short course (5 vs. 10 days). With a low incidence of side effects, and twice a day dosing, it proves to be a useful drug.