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The Annals of Pharmacotherapy Nov 2012To conduct a systematic review of available data on the use of extended or continuous infusion of β-lactam and monobactam therapy in the pediatric population (aged 0-18... (Review)
Review
OBJECTIVE
To conduct a systematic review of available data on the use of extended or continuous infusion of β-lactam and monobactam therapy in the pediatric population (aged 0-18 years).
DATA SOURCES
A literature search was performed using PubMed (1975-May 2012), International Pharmaceutical Abstracts (1970-May 2012), and Web of Science (1977-May 2012) to identify studies for inclusion. In addition, reference citations from identified publications were reviewed. The following search terms were used: pediatric, children, neonate, infant, adolescent, β-lactam, cephalosporin, carbapenem, penicillin, monobactam, continuous infusion, extended infusion, and/or prolonged infusion. Individual names of drugs in each class of antibiotics were also included in the search.
STUDY SELECTION AND DATA EXTRACTION
Randomized controlled clinical trials, pharmacokinetic/pharmacodynamic studies, observational studies, and case reports involving pediatric patients who received extended or continuous infusion of β-lactam or monobactam antibiotics were reviewed. Only English-language publications were included.
DATA SYNTHESIS
One randomized controlled clinical trial, 5 pharmacokinetic studies, 2 pharmacodynamic studies using Monte Carlo simulation, 1 case series, and 7 case reports were included in the analysis. The cephalosporin class has been studied the most and currently represents the only clinical trial using a continuous infusion dosing strategy in pediatric patients. There is limited clinical evidence available to support the use of extended or continuous infusion of β-lactam antibiotics in the pediatric population. Pharmacodynamic studies conducted in this population mirror the current evidence in adults for cefepime and meropenem. The single prospective clinical trial using continuous infusion of ceftazidime failed to demonstrate any clinical benefit over traditional dosing; however, there was equal efficacy.
CONCLUSIONS
More well-designed prospective clinical trials are required to determine the role of extended or continuous infusion of β-lactam antibiotics in treatment of pediatric patients.
Topics: Anti-Bacterial Agents; Child; Computer Simulation; Gram-Positive Bacterial Infections; Humans; Infusions, Intravenous; Monte Carlo Method; beta-Lactams
PubMed: 23115223
DOI: 10.1345/aph.1R216 -
Journal of Clinical Pharmacy and... Dec 2022Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction of cephalosporins. We aimed to describe the clinical features of...
WHAT IS KNOWN AND OBJECTIVE
Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction of cephalosporins. We aimed to describe the clinical features of cephalosporin-induced AGEP and provide a reference for rational clinical use of cephalosporins.
METHODS
We systematically searched Chinese and English databases for cephalosporin-induced TGEP-related case reports, retrospective studies, clinical studies, and review articles published before May 2022.
RESULTS AND DISCUSSION
A total of 43 patients from 35 articles were eligible, of which 28 (65.1%) were female, with a median age of 69 years. A total of 11 cephalosporins were suspected, the most commonly involved were ceftriaxone (41.9%), cephalexin (16.3%), and cefepime (9.3%). AEGP erupted primarily within 14 days after administration, manifested as nonfollicular pustules on an erythematous base, distributed favourably to the extremities (44.2%), trunk (23.3%), face (23.3%), and could involve the oral mucosa (11.6%). During AGEP resolution, the affected area had desquamation (39.5%). The acute phase of the disease may be accompanied by fever (>38.0°C) and elevated neutrophil count (>7500/mm ). Histology of AGEP showed subcorneal pustules (56.3%), intraepidermal cavernous pustules (37.5%), with papillary dermal edema (37.5%), containing neutrophils and eosinophilic infiltration (71.9%). After drug discontinuation, the median time to resolution of AGEP symptoms was 10 days (range 2, 90).
WHAT IS NEW AND CONCLUSION
Cephalosporin-induced AGEP is rare and should be properly diagnosed. This serious cutaneous adverse reaction is self-limiting and has a favourable prognosis, usually resolves with drug interruption, and may require additional interventions, such as topical steroids.
Topics: Humans; Female; Aged; Male; Acute Generalized Exanthematous Pustulosis; Cephalosporins; Retrospective Studies; Ceftriaxone; Exanthema; Monobactams
PubMed: 35909299
DOI: 10.1111/jcpt.13738 -
BMC Pulmonary Medicine Aug 2010Pneumonia, and particularly nosocomial (NP) and ventilator-associated pneumonias (VAP), results in high morbidity and costs. NPs in particular are likely to be caused by... (Review)
Review
BACKGROUND
Pneumonia, and particularly nosocomial (NP) and ventilator-associated pneumonias (VAP), results in high morbidity and costs. NPs in particular are likely to be caused by Pseudomonas aeruginosa (PA), ~20% of which in observational studies are resistant to imipenem. We sought to identify the burden of PA imipenem resistance in pneumonia.
METHODS
We conducted a systematic literature review of randomized controlled trials (RCT) of imipenem treatment for pneumonia published in English between 1993 and 2008. We extracted study, population and treatment characteristics, and proportions caused by PA. Endpoints of interest were: PA resistance to initial antimicrobial treatment, clinical success, microbiologic eradication and on-treatment emergence of resistance of PA.
RESULTS
Of the 46 studies identified, 20 (N = 4,310) included patients with pneumonia (imipenem 1,667, PA 251; comparator 1,661, PA 270). Seven were double blind, and 7 included US data. Comparator arms included a β-lactam (17, [penicillin 6, carbapenem 4, cephalosporin 7, monobactam 1]), aminoglycoside 2, vancomycin 1, and a fluoroquinolone 5; 5 employed double coverage. Thirteen focused exclusively on pneumonia and 7 included pneumonia and other diagnoses. Initial resistance was present in 14.6% (range 4.2-24.0%) of PA isolates in imipenem and 2.5% (range 0.0-7.4%) in comparator groups. Pooled clinical success rates for PA were 45.2% (range 0.0-72.0%) for imipenem and 74.9% (range 0.0-100.0%) for comparator regimens. Microbiologic eradication was achieved in 47.6% (range 0.0%-100.0%) of isolates in the imipenem and 52.8% (range 0.0%-100.0%) in the comparator groups. Resistance emerged in 38.7% (range 5.6-77.8%) PA isolates in imipenem and 21.9% (range 4.8-56.5%) in comparator groups.
CONCLUSIONS
In the 15 years of RCTs of imipenem for pneumonia, PA imipenem resistance rates are high, and PA clinical success and microbiologic eradication rates are directionally lower for imipenem than for comparators. Conversely, initial and treatment-emergent resistance is more likely with the imipenem than the comparator regimens.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Imipenem; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 20796312
DOI: 10.1186/1471-2466-10-45 -
Expert Opinion on Pharmacotherapy Jun 2013Inhaled antibiotics are probably the safest and most effective therapy for Pseudomonas aeruginosa chronic lung infection in cystic fibrosis (CF) patients. (Comparative Study)
Comparative Study Review
INTRODUCTION
Inhaled antibiotics are probably the safest and most effective therapy for Pseudomonas aeruginosa chronic lung infection in cystic fibrosis (CF) patients.
AREAS COVERED
To summarise the available evidence, a systematic review of the three currently available inhaled antibiotics (aztreonam lysine (AZLI), colistin (COL) and tobramycin (TOB)) was performed. The three AZLI placebo-controlled studies showed that the improvements in FEV1 and mean sputum P. aeruginosa density were statistically significant better than with placebo. The two COL placebo-controlled studies involved few patients but showed that COL was better than placebo in terms of maintenance of some pulmonary function parameters. The tobramycin inhalation solution (TIS) and tobramycin inhalation powder studies showed that the efficacy of both formulations was similar but significantly better than placebo. In the comparative studies, TIS showed more efficacy than COL solution, colistin inhalation powder showed non-inferiority to TIS and AZLI was superior to TIS.
EXPERT OPINION
Placebo-controlled and comparative clinical trials have shown that clinical evidence of inhaled antibiotics is very different. The choice of treatment for each individual CF patient must be based on the features of the drug (clinical evidence on efficacy and safety), the inhalation system and the patient characteristics. Development of new inhaled antibiotics will allow new end points of efficacy and therapy regimens to be assessed.
Topics: Administration, Inhalation; Anti-Bacterial Agents; Aztreonam; Chronic Disease; Colistin; Cystic Fibrosis; Humans; Lung Diseases; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Tobramycin
PubMed: 23586963
DOI: 10.1517/14656566.2013.790366 -
The Cochrane Database of Systematic... Jun 2019Cystic fibrosis (CF) a life-limiting inherited disease affecting a number of organs, but classically associated with chronic lung infection and progressive loss of lung...
BACKGROUND
Cystic fibrosis (CF) a life-limiting inherited disease affecting a number of organs, but classically associated with chronic lung infection and progressive loss of lung function. Chronic infection by Burkholderia cepacia complex (BCC) is associated with increased morbidity and mortality and therefore represents a significant challenge to clinicians treating people with CF. This review examines the current evidence for long-term antibiotic therapy in people with CF and chronic BCC infection.
OBJECTIVES
The objective of this review is to assess the effects of long-term oral and inhaled antibiotic therapy targeted against chronic BCC lung infections in people with CF. The primary objective is to assess the efficacy of treatments in terms of improvements in lung function and reductions in exacerbation rate. Secondary objectives include quantifying adverse events, mortality and changes in quality of life associated with treatment.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched online trial registries and the reference lists of relevant articles and reviews.Date of last search: 29 May 2019.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of long-term antibiotic therapy in people with CF and chronic BCC infection.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed risk of bias and assessed the quality of the evidence using GRADE.
MAIN RESULTS
We included one RCT (100 participants) which lasted 52 weeks comparing continuous inhaled aztreonam lysine (AZLI) and placebo in a double-blind RCT for 24 weeks, followed by a 24-week open-label extension and a four-week follow-up period. The average participant age was 26.3 years, 61% were male and average lung function was 56.5% predicted.Treatment with AZLI for 24 weeks was not associated with improvement in forced expiratory volume in one second (FEV), mean difference 0.91% (95% confidence interval (CI) -3.15 to 4.97) (moderate-quality evidence). The median time to the next exacerbation was 75 days in the AZLI group compared to 51 days in the placebo group, but the difference was not significant (P = 0.27) (moderate-quality evidence). Similarly, the number of participants hospitalised for respiratory exacerbations showed no difference between groups, risk ratio (RR) 0.88 (95% CI 0.53 to 1.45) (moderate-quality evidence). Overall adverse events were similar between groups, RR 1.08 (95% CI 0.98 to 1.19) (moderate-quality evidence). There were no significant differences between treatment groups in relation to mortality (moderate-quality evidence), quality of life or sputum density.In relation to methodological quality, the overall risk of bias in the study was assessed to be unclear to low risk.
AUTHORS' CONCLUSIONS
We found insufficient evidence from the literature to determine an effective strategy for antibiotic therapy for treating chronic BCC infection.
Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Aztreonam; Burkholderia Infections; Burkholderia cepacia complex; Chronic Disease; Cystic Fibrosis; Female; Humans; Male
PubMed: 31194880
DOI: 10.1002/14651858.CD013079.pub2 -
The Journal of Antimicrobial... Apr 2024Managing drug-food interactions may help to achieve the optimal action and safety profile of β-lactam antibiotics. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Managing drug-food interactions may help to achieve the optimal action and safety profile of β-lactam antibiotics.
METHODS
We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 β-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices.
RESULTS
Eighteen of 25 β-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or Cmax decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or Cmax increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed β-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor).
CONCLUSIONS
Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low.
Topics: Humans; Cefaclor; beta Lactam Antibiotics; Cefuroxime; Penicillin V; Cephradine; Biological Availability; Antacids; Streptococcus pneumoniae; Anti-Bacterial Agents; beta-Lactams; Monobactams; Minerals; Microbial Sensitivity Tests
PubMed: 38334389
DOI: 10.1093/jac/dkae028