Safety of Single-Dose Oral Cefixime, Intramuscular Ceftriaxone, or Intramuscular Gentamicin for the Treatment of Gonorrhea: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare the incidence and types of adverse effects between 3 recommended treatment options for gonorrhea and to compare the incidence of injection site pain between single-dose intramuscular ceftriaxone and gentamicin. DATA SOURCES: A keyword search of MEDLINE (1966 to September 2020), EMBASE (1947 to September 2020), and International Pharmaceutical Abstracts (1970 to September 2020) was conducted. The electronic search was supplemented with manual screening of references. STUDY SELECTION AND DATA EXTRACTION: Comparator studies reporting adverse effect outcomes of treatment with cefixime, ceftriaxone, or gentamicin for gonorrhea in humans were included. Data extracted included study year, authors, aim, setting, population, dosing protocols, and outcome results. DATA SYNTHESIS: A total of 298 articles were identified, of which 6 met inclusion criteria. Two randomized controlled trials compared ceftriaxone and gentamicin. Four randomized controlled trials compared cefixime and ceftriaxone. No differences were noted for the occurrence of at least 1 adverse effect between gentamicin and ceftriaxone (odds ratio [OR] = 0.81; 95% CI = 0.56-1.18) or between cefixime and ceftriaxone (OR = 1.11; 95% CI = 0.21-5.93). Injection site pain (ceftriaxone and gentamicin) and other adverse effects (all drugs) were common but occurred at similar rates between groups. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Results of this review show a lack of signal for safety concerns with gentamicin-based regimens for the treatment of gonorrhea. Future research should investigate patient acceptability, especially for intramuscular injections. CONCLUSIONS: The use of single-dose cefixime, ceftriaxone, and gentamicin-based regimens for treatment of gonorrhea appears to be safe and acceptable for use in practice.

The negative predictive value of 5-day drug provocation test in nonimmediate beta-lactam allergy in children.

BACKGROUND: Extending the drug provocation test (DPT) period is recommended for patients with suspected nonimmediate beta-lactam antibiotic (BLA) allergy and negative DPT. No consensus has been reached regarding the duration of prolonged provocation. OBJECTIVE: We aimed to determine the negative predictive value (NPV) of the 5-day extended DPT. METHODS: Parents of patients with suspected nonimmediate mild cutaneous reactions with BLAs who had been subjected to 5-day DPT with culprit drugs were questioned by telephone interview about reexposure to the tested drug. Patients with reported reaction during reexposure were reevaluated. Skin tests and serum-specific immunoglobulin E (IgE) analysis were not performed before first DPT. RESULTS: A total of 355 patients had negative results in 5-day DPT. The median age at DPT was 4.2 years, and 52.9% were male. The families of 255 patients (72%) could be contacted. Of these 255 patients, 179 (70%) had used the same drug, and reactions were reported for 6 (3.4%) of those patients, who were subsequently reevaluated. Five of the 6 patients had DPT with amoxicillin-clavulanate and 1 with cefixime. When detailed history was taken, 2 of the 5 patients with amoxicillin-clavulanate reaction were found to have used the drug unintentionally after their reaction to reexposure and did not have any symptoms. One of the patients underwent allergy workup and tested negative, and the other 2 refused the test. The patient with reported cefixime reaction underwent repeated allergy workup and tested negative. Therefore, the NPV of 5-day prolonged DPT was 98.9%. CONCLUSION: The 5-day prolonged DPT has high NPV and seems appropriate in duration for children with suspected nonimmediate-BLA allergy.

Serum sickness-like reactions in Iranian children: a registry-based study in a referral center.

INTRODUCTION AND OBJECTIVES: Considering that no studies have been done on a comprehensive review of Serum sickness-like reactions patients (SSLRs) at a referral center in Iran so far, this study aimed to determine the clinical and laboratory characteristics of children with SSRL in Tehran Children's Medical Center. PATIENTS: The present study was a registry-based study in which the data of 94 SSLRs patients registered in a two-year period were investigated. Confirmation of fever, rash, urticaria, arthralgia / arthritis and history of antibiotic consumption up to three weeks before were the criteria for the diagnosis. RESULTS: Fifty-one (54 %) patients were male with mean age of 56 ±â€¯30 months and there was no significant difference in the age of the two genders. The mean onset of symptoms before hospitalization were 3.8 ±â€¯2.7 days (1-14 days); this mean was significantly higher in males than in females (4.6 ±â€¯2.9 versus 2.9 ±â€¯1.7 days, P-value = 0.003). Among antibiotics, Co-amoxiclav and Cefixime antibiotics had the most frequency by 31 % and 33 %, respectively as the most important incidence factor of SSLRs. The mean duration of consumption of culprit medications in the incidence of SSLRs was 5.6 ±â€¯2.9 days with a range of 1-15 days. CONCLUSIONS: This study showed that among the antibiotics, Co-amoxiclav and Cefixime are more prevalent and a review of prescribing these two antibiotics for the treatment of the children's infections is essential if this finding is confirmed by other Iranian scholars.

Cephalosporin-induced linear IgA dermatosis in a child: Case report and literature review.

Linear IgA dermatosis (LAD) is a rare, subepidermal blistering disease with mucocutaneous involvement. It may be idiopathic or drug induced. We describe a 4-year-old girl who presented with a vesiculobullous eruption after she had been treated with cefixime for urinary tract infection. A diagnosis of drug-induced LAD was made based on clinical, histopathological, and immunofluorescence findings. Naranjo adverse drug reaction algorithm was used to assess imputability resulting with a "probable" association. In literature, cephalosporin antibiotics are rarely reported in association with LAD. To our knowledge, this is the first case of a cefixime-induced LAD among adults and children.

Pilot study of vincristine, oral irinotecan, and temozolomide (VOIT regimen) combined with bevacizumab in pediatric patients with recurrent solid tumors or brain tumors.

BACKGROUND: The combination of vincristine, oral irinotecan, and temozolomide (VOIT regimen) has shown antitumor activity in a pediatric Phase I trial. To further potentiate synergy, we assessed the safety and feasibility of adding bevacizumab to VOIT for children and young adults with recurrent tumors. METHODS: Patients received vincristine (1.5 mg/m(2) on day 1), oral irinotecan (90 mg/m(2) on days 1-5), temozolomide (100-150 mg/m(2) on days 1-5), and bevacizumab (15 mg/kg on day 1) in 3-week cycles, which were repeated for up to six cycles. Cefixime prophylaxis was used to reduce irinotecan-associated diarrhea. RESULTS: Thirteen patients received 36 total cycles. Six of the first 10 patients required dose reductions due to toxicity during the first cycle (n = 3) or subsequent cycles (n = 3), and these grade 3 side effects included prolonged nausea, dehydration, anorexia, neuropathy, diarrhea, and abdominal pain, as well as prolonged grade 4 neutropenia. After reducing daily temozolomide to 100 mg/m(2) , three additional patients tolerated therapy well without the need for dose reductions. Toxicities attributed to bevacizumab were limited to grade 1 epistaxis (1) and grade 2 proteinuria (1). Tumor responses were seen in both patients with Ewing sarcoma. CONCLUSIONS: Reducing temozolomide from 150 to 100 mg/m(2) /day improved tolerability, and treatment with this lower temozolomide dose was feasible and convenient as outpatient therapy. Although responses were seen in Ewing sarcoma, the benefit of adding bevacizumab remains unclear.

[The efficacy and safety of cefixime and amoxicillin/clavulanate in the treatment of asymptomatic bacteriuria in pregnant women: a randomized, prospective, multicenter study].

The study was aimed to the evaluation of efficacy and safety of cefixime and amoxicillin/clavulanate in the treatment of asymptomatic bacteriuria in pregnant women. A prospective, multicenter, randomized study that included 112 pregnant women with asymptomatic bacteriuria was performed. 58 women were randomized in group 1 (cefixime [suprax solutab] 400 mg 1 time a day, 7 days), 54 women were included in group 2 (amoxicillin/clavulanate [amoksiklav] 625 mg 3 times a day, 7 days). The average age of the patients in group 1 was 25.2 +/- 6.6; in group 2--26.6 +/- 5.8 years. Physical examination, evaluation of complaints, collection of data on adverse reactions, and bacteriological analysis of urine were performed after enrollment in the study at visit 2 (day 10 +/- 1) and 3 (day 35 +/- 2). Comparable effectiveness of cefixime and amoxicillin/clavulanate in the treatment of asymptomatic bacteriuria in pregnant women was found. Eradication of the pathogen and sustained bacteriological response were observed in 94.8 and 92.7% of women treated with cefixime, and in 98.2 and 92.5% of women treated with amoxicillin/clavulanate, respectively (P > 0.05). At the same time, the use of amoxicillin/clavulanate compared with cefixime significantly higher was followed by the development of adverse reactions (13% and 1.7; respectively; P = 0.02). Seven-day courses of cefixime at a dose 400 mg 1 time a day and amoxicillin/clavulanate at a dose of 625 mg 3 times a day are high-effective treatment regimens for asymptomatic bacteriuria in pregnant women in Russia. The use of amoxicillin/clavulanate is significantly more often accompanied by the development of adverse reactions compared with cefixime.

Cefixime-induced nonconvulsive status epilepticus.

Nonconvulsive status epilepticus (NCSE) is an epileptic condition lasting >30 min, clinically manifested by an altered mental state and associated with continuous epileptiform activity on the electroencephalogram. NCSE is a common yet still under recognized condition and delay in diagnosis and treatment may be associated with increased mortality as well as cognitive/behavioral consequences. We described an epileptic female patient assuming carbamazepine (900 mg/day) and levetiracetam (3,000 mg/day), seizure free for more than 10 years, who developed NCSE during cefixime treatment, a third-generation cephalosporin compound that along with penicillins is classified within the b-lactam class of antibiotics. In our report we outline the importance and the difficulty to choose secure antibiotic treatment in epileptic patients, we discuss the possible mechanisms by which cephalosporins induce neurotoxicity and the need to stress family components questioning about new drugs assumed. Finally we highlight the value of the EEG recording to diagnose NCSE and treat it adequately and promptly.

Cefixime-induced oculogyric crisis.

Oculogyric crisis is a neurologic adverse event characterized by bilateral dystonic, usually upward, conjugate eye deviations. Cefixime is a third-generation cephalosporin and is widely used in clinical practice in childhood. Confusion, encephalopathy, coma, myoclonus, nonconvulsive status epilepticus, and seizures have been described with the use of cephalosporins. We presented a cefixime-induced oculogyric crisis in a 7-year-old boy during the treatment of urinary tract infection, and this is the first case of cefixime-induced oculogyric crisis whose ocular symptoms gradually disappeared within 48 hours after the drug was discontinued.

Acute localized exanthematous pustulosis because of cefixime in a child: case report and review of pediatric cases.

BACKGROUND: Acute localized exanthematous pustulosis (ALEP), a localized variant of acute generalized exanthematous pustulosis, is characterized by pin-sized, non-follicular, sterile pustules that typically appear on the face, neck, and chest. OBJECTIVE: The purpose of this report is to describe a case of ALEP in an 11-year-old girl because of cefixime and the etiological factors and clinical presentation of ALEP in pediatric group. METHODS: We described a case of ALEP in an 11-year-old girl because of cefixime; a systematic review of the literature was performed to identify the etiological factors and clinical presentation of ALEP in children. RESULTS: We identified eight pediatric cases with ALEP. The causative agent was an herbal product in six cases, and pustular eruption was located on the face. In two cases, responsible agents were drugs (lamotrigine and amoxicillin-clavulanic acid). The eruptions were localized on the penis and extremities, respectively. CONCLUSION: ALEP is very rare in the pediatric age group, and topical/systemic drugs or herbal products may be involved in the etiology.

Cephalosporins-induced intestinal dysbiosis exacerbated pulmonary endothelial barrier disruption in streptococcus pneumoniae-infected mice.

Antibiotic abuse is growing more severe in clinic, and even short-term antibiotic treatment can cause long-term gut dysbiosis, which may promote the development and aggravation of diseases. Cephalosporins as the broad-spectrum antibiotics are widely used for prevention and treatment of community-acquired respiratory tract infection in children. However, their potential consequences in health and disease have not been fully elaborated. In this study, the effects of cefaclor, cefdinir and cefixime on intestinal microbiota and lung injury were investigated in Streptococcus pneumoniae (Spn)-infected mice. The results showed that the proportion of coccus and bacillus in intestinal microbiota were changed after oral administration with cefaclor, cefdinir and cefixime twice for 10 days, respectively. Compared with the Spn-infected group, the proportion of Bifidobacterium and Lactobacillus in intestine were significantly reduced, while Enterococcus and Candida was increased after cephalosporin treatment. Furthermore, 3 cephalosporins could obviously increase the number of total cells, neutrophils and lymphocytes in BALF as well as the serum levels of endotoxin, IL-2, IL-1ß, IL-6 and TNF-α. Mechanically, cephalosporins accelerated Spn-induced pulmonary barrier dysfunction via mediating the mRNA expressions of endothelial barrier-related proteins (Claudin 5, Occludin, and ZO-1) and inflammation-related proteins (TLR4, p38 and NF-κB). However, all of those consequences could be partly reversed by Bifidobacterium bifidum treatment, which was closely related to the elevated acetate production, indicating the protective effects of probiotic against antibiotic-induced intestinal dysbiosis. Therefore, the present study demonstrated that oral administration with cephalosporins not only disrupted intestinal microecological homeostasis, but also increased the risk of Spn infection, resulting in severer respiratory inflammation and higher bacterial loads in mice.

[Efficacy and safety of cefixim and ciprofloxacin in acute cystitis (a multicenter randomized trial)].

A prospective multicenter randomized trial enrolled 104 females aged 18-55 years with acute un-complicated cystitis. The patients were randomized into two groups: 49 patients of group 1 received cefixim in a single dose 400 mg/day for 5 days; 55 patients of group 2 were given ciprofloxacin in a dose 250-500 mg twice a day for 5 days. Clinical and microbiological assessment of efficacy and safety was made before treatment and on treatment day 8 and 28. Significant differences were found between groups 1 and 2 in parameters of bacteriological and clinical efficacy. Eradication of the agent and persistent bacteriological response was seen in 95.9 and 100% patients of group 1, 66 and 100% patients of group 2, respectively. Complete and partial response was observed in 55.1 and 75.5% patients of group 1, 37.3 and 58.1% patients of group 2, respectively. Thus, cefixim in a single dose 400 mg/day for 5 days has a higher microbiological efficacy than ciprofloxacin in a dose 250-500 mg twice a day. Side effects occurred less frequently in the treatment with cefixim.

Acute pyelonephritis in children: antibiotic therapy depending on the clinical context.

Children over 2 years of age with complicated acute pyelonephritis or at risk of complications should first be treated with a parenteral antibiotic, for example ceftriaxone, for 2 to 4 days, then switched to oral antibiotic therapy for a total treatment period of 10 to 14 days, taking into account the results of antimicrobial susceptibility testing. First-choice antibiotic therapy, in the absence of known risk, is oral cefixime for 7 days to 10 days. Second-line treatments include amoxicillin plus clavulanic acid or co-trimoxazole, taking account of the results of antimicrobial susceptibility testing.

A Case of Acute Generalized Exanthematous Pustulosis by Cefixime with Oral Mucosal Involvement.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction characterized by the development of numerous sterile and non-follicular pustules on an erythematous base with no or minimal mucous membrane involvement associated with fever and leucocytosis. Cefixime is a cephalosporin-type beta-lactam antibiotic commonly used for the management of several infections. The Cefixime-induced AGEP cases are known to be rare. Here, we present the case report of a 26-year old female who developed Cefixime-induced AGEP with mucosal membrane involvement. To the best of our knowledge, this is the first case to report the mucosal membrane involvement in Cefixime-induced AGEP. We are presenting this case report to draw the attention on the existence and plethora of symptoms of Cefixime-induced AGEP hoping that the clinicians will reckon these in their differential diagnosis and implement the appropriate management strategies for this rare adverse event in their clinical practice.

Clinical trial protocol to evaluate the efficacy of cefixime in the treatment of early syphilis.

BACKGROUND: Syphilis rates have been increasing both in the USA and internationally with incidence higher among men-who-have-sex-with-men and people living with human immunodeficiency virus (HIV) infection. Currently, benzathine penicillin is the recommended treatment for syphilis in all patients. Global shortages and cost increases in benzathine penicillin call for alternative treatment options. This study evaluates the efficacy of oral cefixime for the treatment of early syphilis. METHODS: We are conducting a randomized, multisite, open-label, non-comparative clinical trial in Los Angeles and Oakland, CA. Eligible participants are ≥ 18 years old, with primary, secondary, or early latent syphilis (rapid plasma reagin [RPR] titer ≥ 1:8). Patients with HIV infection must have a viral load ≤ 200 copies/mL and CD4+ T cell count ≥ 350 cells/µL during the past 6 months. Participants are randomized to receive either 2.4 M IU benzathine penicillin G intramuscularly once or cefixime 400 mg orally twice a day for 10 days. Participants return at 3, 6, and 12 months post-treatment for follow-up RPR serological testing. The primary outcome is the proportion of participants who achieve ≥ 4-fold RPR titer decrease at 3 or 6 months post-treatment. DISCUSSION: Clinical trials evaluating the efficacy of alternative antibiotics to penicillin are urgently needed. TRIAL REGISTRATION: Clinicaltrials.gov NCT03660488 . Registered on 4 September 2018.

Breakthrough pneumonia, meningitis and bloodstream infection due to Streptococcus pneumoniae during cefixime therapy.

Streptococcus pneumoniae is the main pathogen in invasive, life-threatening diseases such as bacteremia, meningitis, and pneumonia. We describe three cases of breakthrough pneumococcal severe life-threatening infections, including two meningitis and one bloodstream infection in patients treated with cefixime for otitis, sinusitis and pneumonia, respectively. Cefixime does not seem to be fully effective in treating invasive pneumococcal diseases. Because penicillin non-susceptibility might be linked to cefixime failure, the prompt knowledge of susceptibility to penicillin in S. pneumoniae might be very useful. Furthermore, MIC of cefixime should be measured because values >0.5 mg/L might be related to failure.

Short- versus long-duration antimicrobial treatment for exacerbations of chronic bronchitis: a meta-analysis.

OBJECTIVES: The aim of this study was to evaluate the comparative effectiveness and safety of short (5 days) and long (7 or 10 days) duration antimicrobial treatment of patients with acute exacerbations of chronic bronchitis (AECB). METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) comparing regimens of the same antibiotic (same dosage and same route of administration) administered for a different time period. We searched PubMed, the Cochrane Central Register of Controlled Trials and reference lists from publications, with no language restrictions. RESULTS: Of the 1031 reports retrieved initially, seven RCTs, enrolling 3083 patients with AECB, met our inclusion criteria. The antimicrobials studied in these seven RCTs were quinolones, cefixime and clarithromycin. There was no difference between the short- and long-duration therapies with regard to treatment success in intention-to-treat [relative risk (RR) = 0.99, 95% confidence interval (CI) 0.95-1.03], clinically evaluable (RR = 0.99, 95% CI 0.96-1.02) or microbiologically evaluable (RR = 0.98, 95% CI 0.93-1.02) patients. Short-duration treatment, when compared with long, was associated with fewer adverse events (RR = 0.84, 95% CI 0.72-0.97). CONCLUSIONS: Short-duration treatment seems to be as effective as and safer than long-duration antimicrobial treatment of patients with AECB. Additional research is required to clarify the long-term outcomes (namely the exacerbation-free interval after the resolution of an initial episode) of the compared regimens.

Cefixime-associated acute generalized exanthematous pustulosis: Rare cases in India.

BACKGROUND: Cefixime is a widely used third-generation cephalosporin schedule H1 drug, which is prescribed for the treatment of otitis media, respiratory tract infections, and uncomplicated urinary tract infections and is effective against infections caused by Enterobacteriaceae and Haemophilus influenzae species in India. The National Coordination Centre (NCC)-Pharmacovigilance Programme of India (PvPI), Indian Pharmacopoeia Commission (IPC), has received rare individual case safety reports (ICSRs) for acute generalized exanthematous pustulosis (AGEP) associated with the use of cefixime. MATERIALS AND METHODS: IPC, NCC-PvPI also acts as a national collaborating center for pharmacovigilance activities under the aegis of Ministry of Health and Family Welfare, Government of India; moreover, it is a member country in global pharmacovigilance system, World Health Organization-Uppsala Monitoring Centre, Sweden. There are more than 250 government/corporate medical colleges and hospitals acting as regional adverse drug reaction monitoring centers, actively functioning under PvPI. Furthermore, various stakeholders including consumers and pharmaceutical industries also play a significant contribution. NCC-PvPI receives spontaneous ICSRs from various stakeholders. RESULTS: NCC-PvPI, IPC has received a total of four spontaneous ICSRs for cefixime-induced AGEP. After clinical evaluation of reported ICSRs, a strong causal relationship was established between AGEP and cefixime and was supported by published literature and histopathological examination of skin. Based on the statistics with positive information component (IC025 Value: 0.17) and proportionality relative risk (PRR:3.4), PvPI considered cefixime-associated AGEP may be a potential signal. CONCLUSION: Hence, initially, AEGP is considered by PvPI as drug safety alert in July 2016. Therefore, to enhance the safety of population in rational usage of medication, as a result, there is a need for physicians and health-care professionals to sensitize about serious adverse reaction while prescribing the cefixime as signal in India.