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.

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.

[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.

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.

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.

Comparison of cefpodoxime proxetil and cefixime in the treatment of acute otitis media in infants and children. Otitis Study Group.

OBJECTIVE: To compare the use of once-a-day cefpodoxime proxetil to once-a-day cefixime in the treatment of acute suppurative otitis media. DESIGN: Randomized, multicenter, investigator-blinded. SETTING: Outpatient. PATIENTS: A total of 368 patients (age 2 months to 17 years) were randomized to receive either cefpodoxime or cefixime in a 2:1 ratio (245 cefpodoxime, 123 cefixime); 236 patients (155 cefpodoxime, 81 cefixime) were evaluable for drug efficacy. INTERVENTIONS: Patients received either cefpodoxime proxetil oral suspension (10 mg/kg/day, once daily for 10 days) or cefixime oral suspension (8 mg/kg/day, once daily for 10 days). MAIN OUTCOME MEASURES: Clinical evaluations were performed before treatment (study day 1), at an interim visit (study day 3 through 6), at the end of therapy (study day 12 through 15), and at final follow-up (study day 25 through 38). Microbiologic evaluations were performed at enrollment and whenever appropriate thereafter. RESULTS: End-of-therapy clinical cure rates in evaluable patients were 56% for the cefpodoxime group and 54% for the cefixime group. Clinical improvement rates were 27% for both groups. Clinical response rates were not significantly different between treatment groups (P = .541; 95% confidence interval = -8.1%, 15.2%). At long-term follow-up, 17% of patients in the cefpodoxime group and 20% in the cefixime group had a recurrence of infection. Drug-related adverse events (eg, diarrhea, diaper rash, vomiting, rash) occurred in 23.3% of cefpodoxime-treated patients and 17.9% of cefixime-treated patients (P = .282). CONCLUSIONS: These findings suggest that cefpodoxime proxetil administered once daily is as effective and safe as cefixime given once daily in the treatment of acute suppurative otitis media in pediatric patients.

Cefetamet pivoxil vs cefaclor in the treatment of acute otitis media in children.

74 children with acute otitis media (AOM) were entered into an observer-blind randomised multicentre general practice study to compare the efficacy and safety of the new third generation oral cephalosporin, cefetamet pivoxil, at a dose of 10 mg/kg twice daily with the efficacy and safety of cefaclor 10 mg/kg twice daily administered for 10 days. Of 36 evaluable patients in the cefaclor treatment group, 28 (78%) were cured, and a further 4 were improved, giving an overall efficacy rate (cure/improvement) of 89%. Of 36 evaluable patients in the cefetamet pivoxil treatment group, 31 (86%) were cured, and a further 4 were improved, giving an overall efficacy rate of 97%. Adverse events were reported in 4 patients: 1 cefaclor recipient and 3 patients in the cefetamet pivoxil treatment group. Diarrhoea, the most frequently observed adverse event, occurred in both treatment groups. The study results indicate that cefetamet pivoxil and cefaclor appear to have similar efficacy and safety in the treatment of AOM in children.

Summary of clinical experience with cefpodoxime proxetil in adults in Japan.

Cefpodoxime proxetil is an oral cephem antibiotic of a new ester type, developed by Sankyo Co., Ltd in Japan. It has a broad antibacterial spectrum, which includes Staphylococcus, and a long half-life, allowing twice-daily administration. In Japan, clinical studies on this drug were performed in various fields, including internal medicine, surgery, urology, otorhinolaryngology, and obstetrics and gynaecology. Good or excellent clinical responses were observed in 2275 of 2902 patients analysed, giving a 78.4% efficacy rate overall. Side effects occurred in 98 patients (2.7%); these were mainly gastrointestinal and included diarrhoea, nausea, and vomiting. Abnormal laboratory test results observed included increased AST in 2.8% (55 of 1973), increased ALT in 3.2% (63 of 1965), and eosinophilia in 2.4% (36 of 1521).

Review of clinical experience in the United States with cefpodoxime proxetil in adults with uncomplicated urinary tract infections.

Two controlled United States trials compared the safety and efficacy of cefpodoxime proxetil (100mg twice daily) with either cefaclor (250mg 3 times daily) or amoxicillin (250mg 3 times daily) in patients with uncomplicated urinary tract infections. Treatment duration was 7 days. 307 of 762 patients treated with cefpodoxime proxetil, 99 of 190 treated with cefaclor, and 57 of 185 treated with amoxicillin were evaluable for efficacy. 311, 99 and 59 pathogens were isolated from cefpodoxime proxetil, cefaclor and amoxicillin patients, respectively, the most common pathogens being Escherichia coli, Klebsiella spp., Proteus mirabilis, and Staphylococcus saprophyticus. Bacteriological cure rates were 80% (247/307), 82% (81/99) and 70% (40/57) for cefpodoxime proxetil, cefaclor and amoxicillin, respectively. Respective clinical cure rates were 79% (242/307), 79% (78/99) and 72% (41/57). Cefpodoxime proxetil was well tolerated, and there was no significant difference between the groups in the overall incidence of adverse experiences. Thus, cefpodoxime proxetil is efficacious and safe in the treatment of patients with uncomplicated urinary tract infections and compares favourably with cefaclor and amoxicillin.

Comparative clinical efficacy of cefetamet pivoxil in lower respiratory tract infection.

Cefetamet pivoxil, because of its activity against respiratory pathogens and its pharmacokinetic behaviour, is expected to have clinical efficacy in the treatment of lower respiratory tract infection (LRTI). This paper presents an overview of clinical trials conducted worldwide to investigate the efficacy and tolerability of cefetamet pivoxil in the treatment of adults and children with LRTI. A total of 626 adult patients, the majority of whom presented with exacerbations of chronic bronchitis (n = 500), received oral cefetamet pivoxil 500 or 1000mg twice daily for 5 to 10 days (n = 351) or a standard comparator agent (n = 275). The comparator agents were amoxicillin (750mg 3 or 4 times daily, or 1000mg twice daily), amoxicillin/clavulanic acid (625mg 3 times daily), or cefaclor (250 or 500mg 3 times daily) administered for 5 to 12 days. A satisfactory clinical outcome (cure + improvement) was achieved in 79 to 94% of evaluable patients. In 336 children, 240 received cefetamet pivoxil at 2 dosage levels (10 or 20 mg/kg twice daily) for 7 to 12 days and 96 received the standard comparator, cefaclor (10 mg/kg 3 times daily). Cefetamet pivoxil was clinically effective at both dosages, and did not differ significantly compared with cefaclor (clinical cure rates of 97 to 99% with cefetamet pivoxil and 96% with cefaclor). A separate analysis of 305 patients with community-acquired pneumonia showed clinical successes in 80 to 100% of adults, 75 to 78% of elderly patients, and 98% of children treated with cefetamet pivoxil.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical trials of cefpodoxime proxetil suspension in paediatrics.

The pharmacokinetics, bacteriological and clinical efficacy, and safety of the suspension formulation of cefpodoxime proxetil, an oral cephalosporin antibacterial, were evaluated in paediatric patients with various infections. With single doses of 3 and 6 mg/kg (cefpodoxime equivalent) a dose response was evident in the serum concentration values. Absorption, as evidenced by serum concentrations and areas under the concentration-time curve, was enhanced when the suspension was administered before a meal. The overall clinical efficacy (defined as an excellent or good response) in evaluable patients (those from whom a pathogen was isolated) was 94.7% (451 of 476). Bacteriological eradication rates were as follows: Gram-positive bacteria 91.3%; Gram-negative bacteria 88.6%, and 90.0% overall. Side effects occurred in 17 (2.29%) patients, and transient and reversible abnormal laboratory values were found in a few patients.

Parenteral-oral switch in the management of paediatric pneumonia.

In phase I of a 2-phase study, 56 evaluable children (0.8 to 5 years) with lobar or segmental pneumonia received intravenous or intramuscular ceftriaxone 50 mg/kg/day for 2 days followed by oral cefetamet pivoxil 20 mg/kg/day in 2 divided doses to complete 7 days of treatment. All patients achieved a clinical cure. In phase II, a randomised open multicentre study, 62 children with pneumonia received an identical regimen to phase I (arm A), and 59 children received ceftriaxone 50 mg/kg/day for 1 day followed by 6 days' treatment with cefetamet pivoxil 20 mg/kg/day (arm B). Patients from phase I and arm A were combined giving a total of 118 evaluable patients in arm A. At the end of treatment, 100% of patients in arm A and 96% in arm B achieved a clinical cure; cure was maintained in 99 and 98% of patients, respectively. Two (4%) patients in arm B failed therapy; in both cases, factors other than treatment failure may have accounted for the poor response. 11 and 12% of patients in treatment arms A and B, respectively, experienced adverse events; gastrointestinal events (nausea and/or vomiting) were reported in 9 and 8% of patients, respectively. In conclusion, 1 or 2 days' treatment with parenteral ceftriaxone before switching to oral cefetamet pivoxil was safe and effective in the treatment of childhood pneumonia. Therefore, parenteral-oral switch is a feasible treatment option in the treatment of serious paediatric community-acquired pneumonia.

Cefpodoxime proxetil in the treatment of lower respiratory tract infections.

Cefpodoxime proxetil is the orally absorbed ester of cefpodoxime, a new third generation cephalosporin. In the gastrointestinal tract, cefpodoxime proxetil is hydrolysed to cefpodoxime, which has potent antibacterial activity against the major bacterial pathogens involved in lower respiratory tract infections: Haemophilus influenzae, Moraxella (Branhamella) catarrhalis (including beta-lactamase-producing strains), and Streptococcus pneumoniae (including amoxicillin-resistant strains). Six randomised comparative studies in patients with lower respiratory tract infections, 5 of which were large (enrollment of more than 200 patients) and double-blind, examined the efficacy and safety of cefpodoxime proxetil. Cefpodoxime proxetil (at a dosage equivalent to 200mg of cefpodoxime) administered twice daily for 5 to 10 days was similar in clinical and bacteriological efficacy to the following: amoxicillin 500mg 3 times daily in the treatment of community-acquired pneumonia; intramuscular ceftriaxone Ig once daily in the treatment of pulmonary infections in hospitalised patients; and to amoxicillin/clavulanic acid 500/125mg 3 times daily in the treatment of acute exacerbations of chronic bronchitis (AECB). Additionally, a dosage equivalent to 100mg or 200mg of cefpodoxime twice daily was similar in clinical and bacteriological efficacy to amoxicillin 250mg 3 times daily in the treatment of bronchitis (acute or AECB). The adverse events noted with cefpodoxime proxetil administration were similar to those associated with other beta-lactam antibacterials and most commonly involved the gastrointestinal tract and skin or mucous membranes. Thus, cefpodoxime proxetil is a useful addition to the antibacterials available for the treatment of infections of the lower respiratory tract.

Cefpodoxime proxetil in the treatment of skin and soft tissue infections.

Patients with skin and soft tissue infections were enrolled in a study comparing 2 dosage regimens of orally administered cefpodoxime proxetil; 204 patients with mild to moderate infections received cefpodoxime proxetil 200mg twice daily and 47 patients with severe infections received 400mg twice daily. Both dosage regimens were given for 7 to 14 days. 132 of 142 (93.0%) evaluable patients in the 200mg group and 22 of 29 (75.9%) in the 400mg group were clinically cured post-therapy, the remainder in both groups being classified as improved. The pathogen eradication rate at the end of therapy in the 200mg group was 161 of 165 (97.6%), and 38 of 38 (100%) in the 400mg group. Adverse reactions (drug-related) were reported by 20 (8.0%) patients overall, and there was no apparent relationship between the dosage group and the incidence of adverse reactions. The most commonly reported reactions involved the gastrointestinal tract (diarrhoea) or female genital tract (vaginitis). Cefpodoxime proxetil appears to be a useful and safe agent in the therapy of skin and soft tissue infections.

A comparison of cefpodoxime proxetil and cefaclor in the treatment of acute exacerbation of COPD in adults.

In this multicenter, observer-blinded study, 301 patients with signs and symptoms of acute bacterial exacerbation of COPD were randomized (2:1) to receive either cefpodoxime proxetil (200 mg, bid) or cefaclor (250 mg, tid) for 10 days. Clinical and microbiologic evaluations were performed before treatment, during therapy (study days 3 to 5), at the end of therapy (3 to 7 days posttreatment), and at long-term follow-up (4 weeks posttreatment). The most common pretreatment isolates were Haemophilus influenzae, Haemophilus parainfluenzae, and Streptococcus pneumoniae. Significantly (p < 0.001) more bacterial isolates were susceptible in vitro to cefpodoxime (233 of 256, 91 percent) than to cefaclor (215 of 255, 84 percent). There were no statistically significant differences between the two drug regimens in eradication of the initial pathogen (cefpodoxime, 116 of 128, 91 percent; cefaclor, 59 of 64, 92 percent) or end-of-therapy clinical response (cure + proved; cefpodoxime, 99 of 100, 99 percent; cefaclor, 45 of 49, 92 percent) rates for evaluable patients. Both drug treatments were well-tolerated, with a similar incidence of drug-related adverse events (cefpodoxime 11 percent, cefaclor 12 percent). Cefpodoxime (bid) was as safe and effective as cefaclor (tid) in the treatment of acute exacerbation of COPD. The less frequent dosing regimen of cefpodoxime may improve patient compliance compared to those antibiotics that require three or four daily doses.

Multicenter trial of cefpodoxime proxetil vs. amoxicillin-clavulanate in acute lower respiratory tract infections in childhood. International Study Group.

Acute lower respiratory tract infections in children are a worldwide public health problem, with an estimated 4 million potentially preventable deaths every year. Until recently, penicillin and related drugs were the treatment of choice for empiric therapy of paediatric lower respiratory tract infections. However, concerns over the emergence of penicillin-resistant strains of Streptococcus pneumoniae and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis have led physicians to turn increasingly towards alternatives, such as the third generation cephalosporins. The oral extended spectrum cephalosporin cefpodoxime proxetil is highly active against the bacterial pathogens commonly associated with childhood lower respiratory tract infections. In order to evaluate its clinical efficacy in children with acute febrile lower respiratory tract infections, an international, multicenter, comparative, randomized open study was conducted in children ages 3 months to 11.5 years. Of 348 cases enrolled, 234 were randomized to cefpodoxime proxetil (8 mg/kg/day twice daily) and 114 to amoxicilin/clavanulate (amoxicillin 40 mg/kg/day 3 times a day). The duration of treatment was 10 days. Pretreatment diagnosis was pneumonia in 292 patients, bronchiolitis in 19 patients and acute bronchitis in 37 patients. Pathogens isolated from 59 cases included H. influenzae (47.5%), S. pneumoniae (23.7%), M. catarrhalis (11.9%) and Haemophilus parainfluenzae (6.8%). Clinical efficacy was evaluable in 278 children at the end of treatment when 95.2% of patients in the cefpodoxime proxetil group and 96.7% of patients in the amoxicillin/clavanulate group showed a satisfactory clinical response (cured or improved). The improvement was sustained at the follow-up visit, 10 to 20 days after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)