Cephalosporin-Induced Neurotoxicity: Clinical Manifestations, Potential Pathogenic Mechanisms, and the Role of Electroencephalographic Monitoring

Grill, Marie F.; Maganti, Rama

doi:10.1345/aph.1l307

Cited by 164 publications

(142 citation statements)

References 42 publications

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“…There were two neurological adverse events in our case series: convulsions and disorientation with progression to stupor. While it is not clear if these events were related to CAZ-AVI use or to other factors, the neurotoxic effects of cephalosporins are described mostly in the elderly and in patients with renal impairment or prior neurologic disease (35). Both patients in our study who developed neurotoxicity were aged 70 years or over, with normal renal function.…”

Section: Resultsmentioning

confidence: 72%

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

Temkin

Torre‐Cisneros

Beović

et al. 2017

Antimicrob Agents Chemother

168

107

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Ceftazidime-avibactam (CAZ-AVI) is a recently approved ␤-lactam-␤-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twentyfive patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro. Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P ϭ 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenemresistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.

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Section: Resultsmentioning

confidence: 72%

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

Temkin

Torre‐Cisneros

Beović

et al. 2017

Antimicrob Agents Chemother

168

107

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“…Risks of long-term use of certain antibiotics as it pertains to promoting the resistance of certain microbes, risk of allergic reaction, risk of intestinal overgrowth presentations, and cardiovascular complications are possible. Cephalosporin antibiotics have also been shown to increase the risk of seizures, particularly in patients with renal impairments (Grill and Maganti 2008). Although we did not encounter this within our study, the potential for neurotoxicity must be carefully examined when considering implementing this treatment regimen.…”

Section: Figmentioning

confidence: 86%

Cefdinir for Recent-Onset Pediatric Neuropsychiatric Disorders: A Pilot Randomized Trial

Murphy

Parker-Athill

Lewin

et al. 2015

Journal of Child and Adolescent Psychopharmacology

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Objective: Previous studies suggest that the unexplained sudden and severe onset of obsessive-compulsive disorder (OCD) and/or tics may be infection or immune precipitated. Beta lactam antibiotics may be neuroprotective beyond their antimicrobial efficacy. We examine the preliminary safety and efficacy of cefdinir in reducing obsessive-compulsive and/or tic severity in children with new-onset symptoms. Method: Twenty subjects were randomized to receive placebo or cefdinir for 30 days for the treatment of recent-onset OCD and/or tics. The placebo group received a comparable inactive treatment matched for taste, color, and consistency. The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) and Yale Global Tic Severity Scale (YGTSS) were the primary outcome measures utilized. Results: Subjects receiving cefdinir saw notable improvements in tic symptoms, with 44.4% showing at least a 25% reduction in YGTSS (mean decrease = 9.5) scores compared with 9.1% of the placebo group (mean decrease = 0.13). Despite improvements, significant group differences were not observed for YGTSS (F [1, 13] = 4.03, p = 0.066) although there were moderate differences between group treatment effects (d = 0.72). For OCD symptoms, subjects receiving cefdinir saw improvements in OCD symptoms, with 33.3% showing at least a 25% reduction in CY-BOCS scores (mean decrease = 7.8) compared with 27.3% of the placebo group (mean decrease = 4.7), but there were also no significant differences for CY-BOCS (F [1, 13] = 0.385, p = 0.546; d = 0.24). Conclusions: Subjects assigned to cefdinir exhibited notable, albeit nonstatistically significant, improvements in tic symptoms, compared with the placebo group. There were also some improvements in OCD symptoms, although these were not significant. Overall, cefdinir was well tolerated. Given these preliminary results, a fully powered study is warranted to explore the efficacy of cefdinir as a therapeutic tool for new-onset pediatric neuropsychiatric symptoms, particularly those that appear to be precipitated by infection.

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“…But concepts are changing, and several studies demonstrate the advantage of TDM for these antibiotics (4,32). Clinicians and pharmacologists agree that certain adverse events like encephalopathy, seizure, and pseudolithiasis occur when doses are excessive (2,8,12,15,16,19,23,27). Various infectious diseases, e.g., endocarditis, meningitis, and osteomyelitis, require administration of high-dose antibiotics via intermittent or continuous infusion (6,36,38).…”

mentioning

confidence: 99%

Simultaneous Determination of 12 β-Lactam Antibiotics in Human Plasma by High-Performance Liquid Chromatography with UV Detection: Application to Therapeutic Drug Monitoring

Verdier

Tribut

Tattevin

et al. 2011

Antimicrob Agents Chemother

131

100

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A rapid and specific high-performance liquid chromatography method with UV detection (HPLC-UV) for the simultaneous determination of 12 beta-lactam antibiotics (amoxicillin, cefepime, cefotaxime, ceftazidime, ceftriaxone, cloxacillin, imipenem, meropenem, oxacillin, penicillin G, piperacillin, and ticarcillin) in small samples of human plasma is described. Extraction consisted of protein precipitation by acetonitrile. An Atlantis T3 analytical column with a linear gradient of acetonitrile and a pH 2 phosphoric acid solution was used for separation. Wavelength photodiode array detection was set either at 210 nm, 230 nm, or 298 nm according to the compound. This method is accurate and reproducible (coefficient of variation [CV] < 8%), allowing quantification of beta-lactam plasma levels from 5 to 250 g/ml without interference with other common drugs. This technique is easy to use in routine therapeutic drug monitoring of beta-lactam antibiotics.

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Cephalosporin-Induced Neurotoxicity: Clinical Manifestations, Potential Pathogenic Mechanisms, and the Role of Electroencephalographic Monitoring

Cited by 164 publications

References 42 publications

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

Cefdinir for Recent-Onset Pediatric Neuropsychiatric Disorders: A Pilot Randomized Trial

Simultaneous Determination of 12 β-Lactam Antibiotics in Human Plasma by High-Performance Liquid Chromatography with UV Detection: Application to Therapeutic Drug Monitoring

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