RESUMO
In our tertiary care center, the reported susceptibility of E. coli blood isolates to amoxicillin/clavulanic acid exceeded 90% in 2005 and showed a progressive decrease to 50% by 2017. In this study, we investigate whether there is a real increase in resistant E. coli strains or if this apparent decline in reported susceptibility might be attributed to the substitution of CLSI by EUCAST guidelines in 2014. We randomly selected 237 E. coli blood isolates (stored at - 80 °C) from 1985 to 2018 and reassessed their MIC values, applying both the CLSI (fixed ratio of clavulanic acid) and EUCAST guidelines (fixed concentration of clavulanic acid). In parallel, the susceptibility of these isolates was retested by disk diffusion, according to the EUCAST guidelines. Whole genome sequencing was successfully performed on 233 of the 237 isolates. In only 130 of the 237 isolates (55.0%), testing according to the EUCAST and CLSI criteria delivered identical MIC values for amoxicillin/clavulanic acid. In 64 of the 237 isolates (27.0%), the MIC values diverged one dilution; in 38 (16.0%), two dilutions; and in five (2.1%), three dilutions. From these 107 discrepant results, testing according to EUCAST methodology revealed more resistant profiles in 93 E. coli strains (94.1%). Also, phenotypical susceptibility testing according to EUCAST guidelines tends to correlate better with the presence of beta-lactamase genes compared to CLSI testing procedure. This study highlights the low agreement between EUCAST and CLSI methodologies when performing MIC testing of amoxicillin/clavulanic acid. More strains are categorized as resistant when EUCAST guidelines are applied. The low agreement between EUCAST and CLSI was confirmed by WGS, since most of EUCAST resistant/CLSI sensitive isolates harbored beta-lactamase genes.
Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/microbiologia , Escherichia coli/efeitos dos fármacos , Combinação Amoxicilina e Clavulanato de Potássio/normas , Antibacterianos/normas , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana , Escherichia coli/enzimologia , Escherichia coli/genética , Escherichia coli/fisiologia , Infecções por Escherichia coli/tratamento farmacológico , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Europa (Continente) , Humanos , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , beta-Lactamases/metabolismoRESUMO
Increasing burden of carbapenem resistance and resultant difficult-to-treat infections are of particular concern due to the lack of effective and safe treatment options. More recently, several new agents with activity against certain multidrug-resistant (MDR) and extensive drug-resistant (XDR) Gram-negative pathogens have been approved for clinical use. These include ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, and cefiderocol. For the management of MBL infections, clinically used triple combination comprising ceftazidime-avibactam and aztreonam is hindered due to non-availability of antimicrobial susceptibility testing methods and lack of information on potential drug-drug interaction leading to PK changes impacting its safety and efficacy. Moreover, in several countries including Indian subcontinent and developing countries, these new agents are yet to be made available. Under these circumstances, polymyxins are the only last resort for the treatment of carbapenem-resistant infections. With the recent evidence of suboptimal PK/PD particularly in lung environment, limited efficacy and increased nephrotoxicity associated with polymyxin use, the Clinical and Laboratory Standards Institute (CLSI) has revised both colistin and polymyxin B breakpoints. Thus, polymyxins 'intermediate' breakpoint for Enterobacterales, P. aeruginosa, and Acinetobacter spp. are now set at ≤ 2 mg/L, implying limited clinical efficacy even for isolates with the MIC value 2 mg/L. This change has questioned the dependency on polymyxins in treating XDR infections. In this context, recently approved cefiderocol and phase 3 stage combination drug cefepime-zidebactam assume greater significance due to their potential to act as polymyxin-supplanting therapies.
Assuntos
Antibacterianos/uso terapêutico , Polimixinas/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/normas , Proteínas de Bactérias/classificação , Proteínas de Bactérias/metabolismo , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Países em Desenvolvimento , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Testes de Sensibilidade Microbiana/normas , Polimixinas/farmacologia , Polimixinas/normas , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/uso terapêutico , beta-Lactamases/classificação , beta-Lactamases/metabolismoRESUMO
BACKGROUND: Drowning is a cause of significant global mortality. The mechanism of injury involves inhalation of water, lung injury and hypoxia. This systematic review addressed the following question: In drowning patients with lung injury, what is the evidence from primary studies regarding treatment strategies and subsequent patient outcomes? METHODS: The search strategy utilised PRISMA guidelines. Databases searched were MEDLINE, EMBASE, CINAHL, Web of Science and SCOPUS. There were no restrictions on publication date or age of participants. Quality of evidence was evaluated using GRADE methodology. RESULTS: Forty-one papers were included. The quality of evidence was very low. Seventeen papers addressed the lung injury of drowning in their research question and 24 had less specific research questions, however included relevant outcome data. There were 21 studies regarding extra-corporeal life support, 14 papers covering the theme of ventilation strategies, 14 addressed antibiotic use, seven papers addressed steroid use and five studies investigating diuretic use. There were no clinical trials. One retrospective comparison of therapeutic strategies was found. There was insufficient evidence to make recommendations as to best practice when supplemental oxygen alone is insufficient. Mechanical ventilation is associated with barotrauma in drowning patients, but the evidence predates the practice of lung protective ventilation. There was insufficient evidence to make recommendations regarding adjuvant therapies. CONCLUSIONS: Treating the lung injury of drowning has a limited evidentiary basis. There is an urgent need for comparative studies of therapeutic strategies in drowning.
Assuntos
Afogamento/fisiopatologia , Lesão Pulmonar/etiologia , Resultado do Tratamento , Antibacterianos/normas , Antibacterianos/uso terapêutico , Barotrauma/etiologia , Barotrauma/terapia , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/normas , Humanos , Lesão Pulmonar/terapia , Respiração Artificial/métodos , Respiração Artificial/normasRESUMO
BACKGROUND: Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding. METHODS: ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The primary endpoint was 28-day ACM. The key secondary endpoint was clinical response at test-of-cure. Participants with vHABP were a prospectively defined subgroup, but subgroup analyses were not powered for noninferiority testing. We compared baseline and treatment factors, efficacy, and safety between ceftolozane/tazobactam and meropenem in participants with vHABP. We also conducted a retrospective multivariable logistic regression analysis in this subgroup to determine the impact of treatment arm on mortality when adjusted for significant prognostic factors. RESULTS: Overall, 99 participants in the ceftolozane/tazobactam and 108 in the meropenem arm had vHABP. 28-day ACM was 24.2% and 37.0%, respectively, in the intention-to-treat population (95% confidence interval [CI] for difference: 0.2, 24.8) and 18.2% and 36.6%, respectively, in the microbiologic intention-to-treat population (95% CI 2.5, 32.5). Clinical cure rates in the intention-to-treat population were 50.5% and 44.4%, respectively (95% CI - 7.4, 19.3). Baseline clinical, baseline microbiologic, and treatment factors were comparable between treatment arms. Multivariable regression identified concomitant vasopressor use and baseline bacteremia as significantly impacting ACM in ASPECT-NP; adjusting for these two factors, the odds of dying by day 28 were 2.3-fold greater when participants received meropenem instead of ceftolozane/tazobactam. CONCLUSIONS: There were no underlying differences between treatment arms expected to have biased the observed survival advantage with ceftolozane/tazobactam in the vHABP subgroup. After adjusting for clinically relevant factors found to impact ACM significantly in this trial, the mortality risk in participants with vHABP was over twice as high when treated with meropenem compared with ceftolozane/tazobactam. TRIAL REGISTRATION: clinicaltrials.gov, NCT02070757. Registered 25 February, 2014, clinicaltrials.gov/ct2/show/NCT02070757.
Assuntos
Cefalosporinas/normas , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Meropeném/normas , Tazobactam/normas , Idoso , Antibacterianos/farmacologia , Antibacterianos/normas , Antibacterianos/uso terapêutico , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Método Duplo-Cego , Estudos de Equivalência como Asunto , Feminino , Humanos , Modelos Logísticos , Masculino , Meropeném/farmacologia , Meropeném/uso terapêutico , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Estudos Retrospectivos , Tazobactam/farmacologia , Tazobactam/uso terapêuticoRESUMO
BACKGROUND: The bacterial density of Pseudomonas aeruginosa is closely related to its pathogenicity. We evaluated the effect of airway P. aeruginosa density on the clinical course of mechanically ventilated patients and the therapeutic efficacy of antibiotics. METHODS: We retrospectively analyzed data of mechanically ventilated ICU patients with P. aeruginosa isolated from endotracheal aspirates. Patients were divided into three groups according to the peak P. aeruginosa density during ICU stay: low (≤ 104 cfu/mL), moderate (105â106 cfu/mL), and high (≥ 107 cfu/mL) peak density groups. The relationship between peak P. aeruginosa density and weaning from mechanical ventilation, risk factors for isolation of high peak density of P. aeruginosa, and antibiotic efficacy were investigated using multivariate and propensity score-matched analyses. RESULTS: Four-hundred-and-sixty-one patients were enrolled. Patients with high peak density of P. aeruginosa had higher inflammation and developed more severe respiratory infections. High peak density of P. aeruginosa was independently associated with few ventilator-free days on day 28 (P < 0.01) and increased ICU mortality (P = 0.047). Risk factors for high peak density of P. aeruginosa were prolonged mechanical ventilation (odd ratio [OR] 3.07 95% confidence interval [CI] 1.35â6.97), non-antipseudomonal cephalosporins (OR 2.17, 95% CI 1.35â3.49), hyperglycemia (OR 2.01, 95% CI 1.26â3.22) during ICU stay, and respiratory diseases (OR 1.9, 95% CI 1.12â3.23). Isolation of commensal colonizer was associated with lower risks of high peak density of P. aeruginosa (OR 0.43, 95% CI 0.26â0.73). Propensity score-matched analysis revealed that antibiotic therapy for patients with ventilator-associated tracheobronchitis improved weaning from mechanical ventilation only in the high peak P. aeruginosa group. CONCLUSIONS: Patients with high peak density of P. aeruginosa had worse ventilator outcome and ICU mortality. In patients with ventilator-associated tracheobronchitis, antibiotic therapy was associated with favorable ventilator weaning only in the high peak P. aeruginosa density group, and bacterial density could be a good therapeutic indicator for ventilator-associated tracheobronchitis due to P. aeruginosa.
Assuntos
Antibacterianos/normas , Pseudomonas aeruginosa/isolamento & purificação , Respiração Artificial/estatística & dados numéricos , APACHE , Idoso , Antibacterianos/farmacologia , Distribuição de Qui-Quadrado , Feminino , Mortalidade Hospitalar/tendências , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Japão/epidemiologia , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pontuação de Propensão , Pseudomonas aeruginosa/patogenicidade , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Skin necrosis is one of the most severe complications following filler injections, and can result in permanent aesthetic defects. Although an increasing number of studies have addressed the management of dermal filler complications, no study has described the spectrum of microbial pathogens. The aim of this study was to delineate the bacterial profile and prognostic factors of filler-related skin necrosis by reviewing the clinical and microbiological features of these patients. A retrospective medical record review of patients undergoing treatment for skin necrosis induced by fillers was conducted. In total, 10 cases were identified, with injection sites being the nasolabial fold (70%; n = 7), nasal dorsum (20%; n = 2) and nasal tip (10%; n = 1). Reviewing the culture results, the true culture-positive rate was found to be 50% after cases of contamination were excluded. To avoid permanent sequelae, all physicians should be aware of possible secondary infections when treating filler-induced skin necrosis.
Assuntos
Preenchedores Dérmicos/efeitos adversos , Necrose/induzido quimicamente , Necrose/microbiologia , Dermatopatias/etiologia , Adulto , Antibacterianos/normas , Antibacterianos/uso terapêutico , Técnicas de Cultura/métodos , Técnicas de Cultura/estatística & dados numéricos , Preenchedores Dérmicos/administração & dosagem , Feminino , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Reação no Local da Injeção/microbiologia , Reação no Local da Injeção/patologia , Pessoa de Meia-Idade , Sulco Nasogeniano/microbiologia , Sulco Nasogeniano/patologia , Necrose/diagnóstico , Necrose/terapia , Nariz/microbiologia , Nariz/patologia , Prognóstico , Reepitelização/fisiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Dermatopatias/patologiaRESUMO
INTRODUCTION: International travel results in an increased risk of colonization and infection with multidrug-resistant organisms. This study aimed to determine if recent travel to Mexico affects the rate of uropathogen-antibiotic susceptibility mismatch (UASM) in outpatients treated for urinary tract infection (UTI) in a South Texas emergency department (ED). METHODS: A retrospective cohort of adult patients presenting to the ED and treated outpatient for UTI from October 1, 2014, to February 25, 2020, was conducted at a community hospital located within approximately 15 miles of the United States-Mexico border. Rates of UASM were compared between patients with a history of recent travel to Mexico and those who have not recently traveled. RESULTS: A total of 192 patients were included, with 64 in the travel to Mexico group and 128 in the no travel group. UASM was significantly higher in the recent travel to Mexico group when compared to the no travel group (RR 1.49, 95% CI 1.03-2.13). Antibiotics most commonly associated with UASM included fluoroquinolones, cephalexin, and sulfamethoxazole-trimethoprim. There was no significant difference between the rates of resistance to first-line agents for the treatment of UTI among the two groups. CONCLUSION: In addition to known antibiotic resistance risk factors, recent travel to Mexico may increase the risk of UASM for ED patients with UTI. Considering the potential consequences of UTI treatment failure, antimicrobial stewardship services in the ED should include screening for antibiotic resistance risk factors and urine culture follow-up to ensure appropriate outpatient antibiotic therapy, especially among patients with recent international travel.
Assuntos
Antibacterianos/normas , Suscetibilidade a Doenças/microbiologia , Infecções Urinárias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Coortes , Serviço Hospitalar de Emergência/organização & administração , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Retrospectivos , Viagem , Infecções Urinárias/fisiopatologiaRESUMO
BACKGROUND: Impetigo is a contagious bacterial infection that affects the superficial skin layers. Increasing worldwide antimicrobial resistance (AMR) to existing topical agents commonly prescribed to treat impetigo is central to treatment failure. The Worldwide Health Organization developed a global action plan on AMR, but omitted information about AMR stewardship programs for topical antibiotics. OBJECTIVES: The review aims to provide information to clinicians and stakeholders regarding AMR and antimicrobial stewardship on topical antimicrobial drugs for impetigo treatment. METHODS: The literature searches reviewed the status of AMR to current topical antibiotics in impetigo, current therapeutic behavior, and concordance with antimicrobial stewardship principles. Two international panels convened to discuss the output of the searches, and the results of the panel discussions were used in the development of the manuscript. RESULTS: The literature search included clinical trials, research studies, clinical guidelines, consensus papers, and reviews (if they provided original data), published between January 2008 and May 2019. The articles were selected based on clinical relevancy of impetigo management, clinical efficacy, and safety of the treatment and antimicrobial resistance. The searches resulted in one-hundred and ninety-eight articles. After applying the eligibility criteria, nineteen articles met inclusion criteria and were considered in the present review. CONCLUSIONS: While published antimicrobial stewardship guidelines have focused on systemic antibiotics, few studies have attempted to evaluate topical antibiotic prescribing practices for impetigo treatment. Many of the topical impetigo treatments currently in use have developed resistance. The appropriate use of topical ozenoxacin can help eradicate impetigo while minimizing AMR.J Drugs Dermatol. 20(4):366-372. doi:10.36849/JDD.5795.
Assuntos
Antibacterianos/farmacologia , Gestão de Antimicrobianos/normas , Impetigo/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Administração Cutânea , Aminopiridinas/farmacologia , Aminopiridinas/normas , Aminopiridinas/uso terapêutico , Antibacterianos/normas , Antibacterianos/uso terapêutico , Prescrições de Medicamentos/normas , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Guias de Prática Clínica como Assunto , Quinolonas/farmacologia , Quinolonas/normas , Quinolonas/uso terapêutico , Staphylococcus aureus/isolamento & purificação , Resultado do TratamentoRESUMO
Updated Clostridioides difficile infection (CDI) guidelines published in 2018 recommend vancomycin as first-line treatment. Of 833 community-onset CDI cases in metropolitan Atlanta, Georgia in 2018, over half did not receive first-line treatment, although guideline adherence increased over the year. Second-line treatment was more common in patients treated in ambulatory settings.
Assuntos
Antibacterianos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/tratamento farmacológico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Adulto , Idoso , Antibacterianos/normas , Clostridioides difficile/fisiologia , Infecções por Clostridium/microbiologia , Estudos de Coortes , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Georgia , Guias como Assunto , Humanos , Masculino , Metronidazol/normas , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Vancomicina/normas , Vancomicina/uso terapêuticoRESUMO
The ever-growing commercialization of poor-quality and substandard medicines, especially anti-infectives characterized by inadequate postmarket surveillance by stakeholders remains a major global health challenge, particularly in developing countries, where antibiotic drug resistance and its repercussions on human health remain dominant. This research sought to evaluate the pharmaceutical quality of six randomly selected brands of cefuroxime axetil tablets (250 mg) marketed in the Greater Accra region of Ghana. The selected brands were coded and subjected to both compendial and noncompendial tests. Statistical analysis and model-independent parameter (similarity factor, f2) were employed in analyzing the dissolution profiles of all the brands. All brands including the reference brand conformed to the pharmacopeial specifications for both compendial and noncompendial tests, indicating that they were of good quality. However, there were significant variations (p < 0.05) in the disintegration time amongst the various brands. All the brands had ƒ2 values > 50 indicating similarity of their drug release profiles with the innovator. Hence, all the sampled cefuroxime axetil brands can be considered as pharmaceutical equivalents to the innovator drug. These brands can, therefore, be used as a substitute for the innovator drug by physicians to patients in cases of unaffordability or unavailability of the innovator brand.
Assuntos
Antibacterianos/normas , Cefuroxima/análogos & derivados , Cefuroxima/análise , Cefuroxima/normas , Medicamentos Falsificados , Armazenamento de Medicamentos , Gana , Controle de Qualidade , Comprimidos/normasRESUMO
AIM OF THE STUDY: The aim of the current study was to develop collagen-based bi-layered composite dressings with antibacterial property and evaluate the efficiency for wound healing. MATERIALS AND METHODS: A bi-layered composite wound dressing was fabricated using two marine biomacromolecules (collagen and chitosan or carboxymethyl chitosan). Non-crosslinked and N-Ethyl-N'-(3-dimethylaminopropyl) carbodiimide/N-Hydroxy succinimide (EDC/NHS) cross-linked collagen sponges fabricated by vacuum freeze-drying technology was used as the inner layer. The medical spun-laced nonwoven coated with chitosan and carboxymethyl chitosan was used as the outer layer. The antibacterial activities against E. coli and S. aureus were evaluated by the inhibition zone assay. Deep second-degree scald model was performed to evaluate the efficiency of bi-layered composite dressings for wound healing. RESULTS: In view of comprehensive evaluation of appearance and in vitro antibacterial activity, medical spun-laced nonwoven coated with 3% of chitosan solution was chosen to be used as the optimized preparation conditions to produce the outer layer of composite dressing, which acted as a barrier against microorganisms and provided mechanical support. Furthermore, the results of wound closure and histopathological analysis indicated that EDC/NHS cross-linked collagen-based bi-layered composite dressing was superior to non-crosslinked and commercial products, which stimulated the wound healing process and accomplished deep second-degree scalded skin healing within a time span of 28 days. CONCLUSION: The EDC/NHS cross-linked collagen-based bi-layered composite dressing had immense potential to be applied for an ideal wound dressing for more efficient and faster wound healing. Therefore, the findings provided the essential theoretical basis for great potential of collagen-based composite dressing used in wound healing applications.
Assuntos
Antibacterianos/normas , Bandagens/normas , Colágeno/farmacologia , Cicatrização/efeitos dos fármacos , Análise de Variância , Animais , Antibacterianos/administração & dosagem , Bandagens/estatística & dados numéricos , Colágeno/uso terapêutico , Modelos Animais de Doenças , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
BACKGROUND: Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 years are viral. This study aims to safely reduce antibiotic prescriptions in children under 5 years with suspected lower RTI at the emergency department (ED), by implementing a clinical decision rule. METHODS AND FINDINGS: In a stepped-wedge cluster randomised trial, we included children aged 1-60 months presenting with fever and cough or dyspnoea to 8 EDs in The Netherlands. The EDs were of varying sizes, from diverse geographic and demographic regions, and of different hospital types (tertiary versus general). In the pre-intervention phase, children received usual care, according to the Dutch and NICE guidelines for febrile children. During the intervention phase, a validated clinical prediction model (Feverkidstool) including clinical characteristics and C-reactive protein (CRP) was implemented as a decision rule guiding antibiotic prescription. The intervention was that antibiotics were withheld in children with a low or intermediate predicted risk of bacterial pneumonia (≤10%, based on Feverkidstool). Co-primary outcomes were antibiotic prescription rate and strategy failure. Strategy failure was defined as secondary antibiotic prescriptions or hospitalisations, persistence of fever or oxygen dependency up to day 7, or complications. Hospitals were randomly allocated to 1 sequence of treatment each, using computer randomisation. The trial could not be blinded. We used multilevel logistic regression to estimate the effect of the intervention, clustered by hospital and adjusted for time period, age, sex, season, ill appearance, and fever duration; predicted risk was included in exploratory analysis. We included 999 children (61% male, median age 17 months [IQR 9 to 30]) between 1 January 2016 and 30 September 2018: 597 during the pre-intervention phase and 402 during the intervention phase. Most children (77%) were referred by a general practitioner, and half of children were hospitalised. Intention-to-treat analyses showed that overall antibiotic prescription was not reduced (30% to 25%, adjusted odds ratio [aOR] 1.07 [95% CI 0.57 to 2.01, p = 0.75]); strategy failure reduced from 23% to 16% (aOR 0.53 [95% CI 0.32 to 0.88, p = 0.01]). Exploratory analyses showed that the intervention influenced risk groups differently (p < 0.01), resulting in a reduction in antibiotic prescriptions in low/intermediate-risk children (17% to 6%; aOR 0.31 [95% CI 0.12 to 0.81, p = 0.02]) and a non-significant increase in the high-risk group (47% to 59%; aOR 2.28 [95% CI 0.84 to 6.17, p = 0.09]). Two complications occurred during the trial: 1 admission to the intensive care unit during follow-up and 1 pleural empyema at day 10 (both unrelated to the study intervention). Main limitations of the study were missing CRP values in the pre-intervention phase and a prolonged baseline period due to logistical issues, potentially affecting the power of our study. CONCLUSIONS: In this multicentre ED study, we observed that a clinical decision rule for childhood pneumonia did not reduce overall antibiotic prescription, but that it was non-inferior to usual care. Exploratory analyses showed fewer strategy failures and that fewer antibiotics were prescribed in low/intermediate-risk children, suggesting improved targeting of antibiotics by the decision rule. TRIAL REGISTRATION: Netherlands Trial Register NTR5326.
Assuntos
Antibacterianos/normas , Gestão de Antimicrobianos/normas , Regras de Decisão Clínica , Prescrições de Medicamentos/normas , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/métodos , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Lactente , Masculino , Países Baixos/epidemiologia , Infecções Respiratórias/diagnósticoRESUMO
BACKGROUND: Global recognition of antimicrobial resistance (AMR) as an urgent public health problem has galvanized national and international efforts. Chief among these are interventions to curb the overuse and misuse of antibiotics. However, the impact of these initiatives is not fully understood, making it difficult to assess the expected effectiveness and sustainability of further policy interventions. We conducted a systematic review to summarize existing evidence for the impact of nationally enforced interventions to reduce inappropriate antibiotic use in humans. METHODS: We searched seven databases and examined reference lists of retrieved articles. To be included, articles had to evaluate the impact of national responsible use initiatives. We excluded studies that only described policy implementations. RESULTS: We identified 34 articles detailing interventions in 21 high- and upper-middle-income countries. Interventions addressing inappropriate antibiotic access included antibiotic committees, clinical guidelines and prescribing restrictions. There was consistent evidence that these were effective at reducing antibiotic consumption and prescription. Interventions targeting inappropriate antibiotic demand consisted of education campaigns for healthcare professionals and the general public. Evidence for this was mixed, with several studies showing no impact on overall antibiotic consumption. CONCLUSIONS: National-level interventions to reduce inappropriate access to antibiotics can be effective. However, evidence is limited to high- and upper-middle-income countries, and more evidence is needed on the long-term sustained impact of interventions. There should also be a simultaneous push towards standardized outcome measures to enable comparisons of interventions in different settings.
Assuntos
Antibacterianos/normas , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/métodos , Padrões de Prática Médica , Gestão de Antimicrobianos/legislação & jurisprudência , Gestão de Antimicrobianos/estatística & dados numéricos , Farmacorresistência Bacteriana , Saúde Global/normas , Saúde Global/estatística & dados numéricos , HumanosRESUMO
In this study, the development of our purpose-made capacitively coupled contactless conductivity detection (C4 D) for CE is reported. These systems have been employed as a simple, versatile, and cost-effective analytical tool. CE-C4 D devices, whose principle is based on the control of the ion movements under an electrical field, can be constructed even with a modest financial budget and limited infrastructure. A featured application was developed for quality control of antimicrobial drugs using CE-C4 D, with most recent work on determination of aminoglycoside and glycopeptide antibiotics being communicated. For aminoglycosides, the development of CE-C4 D methods was adapted to two categories. The first one includes drugs (liquid or powder form) for intravenous injection, containing either amikacin, streptomycin, kanamycin A, or kanamycin B. The second one covers drugs for eye drops (liquid or ointment form), containing either neomycin, tobramycin, or polymyxin. The CE-C4 D method development was also made for determination of some popular glycopeptide antibiotics in Vietnam, including vancomycin and teicoplanin. The best detection limit achieved using the developed CE-C4 D methods was 0.5 mg/L. Good agreement between results from CE-C4 D and the confirmation method (HPLC- Photometric Diode Array ) was achieved, with their result deviations less than 8% and 13% for aminoglycoside and glycopeptide antibiotics, respectively.
Assuntos
Antibacterianos , Eletroforese Capilar/métodos , Aminoglicosídeos/análise , Aminoglicosídeos/química , Aminoglicosídeos/normas , Antibacterianos/análise , Antibacterianos/química , Antibacterianos/normas , Condutividade Elétrica , Eletroforese Capilar/economia , Eletroforese Capilar/instrumentação , Desenho de Equipamento , Glicopeptídeos/análise , Glicopeptídeos/química , Glicopeptídeos/normas , Limite de Detecção , Modelos Lineares , Controle de Qualidade , Reprodutibilidade dos Testes , VietnãRESUMO
OBJECTIVE: To assess the quality of antibiotics sampled from authorised sales outlets (ATs) (i.e. hospitals/health centres, pharmacies and licensed chemical shops) and unauthorised sales outlets (UATs) (mainly street vendors) in Ghana and to explore the health-seeking behaviour of medicine consumers. METHODS: The contents of 14 active pharmaceutical ingredients (APIs) in 348 sampled products were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Data on health-seeking practices were collected through entry and exit interviews and field observations from ATs and UATs. RESULTS: It was observed that 66.38% of all sampled antibiotic products were substandard; they either contained less (<90%) or more API (>110%) than the label claim. Medicines from UATs recorded substantially less API contents than those from ATs (F(2,419) = 43.01, P < 0.0001). For example, 90.54% of street vendor samples contained < 90% of the APIs. 75.93% of consumers often sought self-treatment with drugs without a prescription from UATs, as they perceived UATs as easily accessible, trustworthy and knowledgeable, and their medicines as inexpensive. These consumers rather thought of the formal healthcare providers as alternative sources. CONCLUSIONS: Consumers who purchase from UATs are at high risk of receiving substandard medicines. The quality of medicines in the national healthcare system, in the supply chain and in the distribution system needs to be monitored regularly to reduce the incidence of substandard medicines and their impact on antimicrobial resistance. The fight against substandard medicines needs to incorporate a full understanding of socioeconomic factors that drive consumer decisions regarding their health and choice of healthcare providers.
OBJECTIF: Evaluer la qualité des antibiotiques prélevés auprès des vendeurs autorisés (VA) (c'est-à-dire les hôpitaux/centres de santé, les pharmacies et les magasins de produits chimiques agréés) et des vendeurs non autorisés (VNA) (principalement les vendeurs de rue) au Ghana et étudier le comportement des utilisateurs de médicaments en quête de santé. MÉTHODES: Le contenu de 14 principes actifs (PA) pharmaceutiques dans 348 produits échantillonnés a été déterminé à l'aide d'une méthode validée de chromatographie liquide et de spectrométrie de masse en tandem (LC-MS/MS). Les données sur les pratiques de recherche de santé ont été collectées par le biais d'entretiens d'entrée et de sortie, et d'observations sur le terrain des VA et des VNA. RÉSULTATS: Il a été observé que 66,38% de tous les produits antibiotiques échantillonnés étaient inférieurs aux normes; ils contenaient soit moins (<90%), soit plus de PA (>110%) que ce qui était indiqué sur la notice. Les médicaments provenant des VNA ont enregistré une quantité de PA sensiblement inférieure à celle des VA (F(2,419) = 43.01, P < 0,0001). Par exemple, 90,54% des échantillons de vendeurs de rue contenaient <90% de PA. 75,93% des utilisateurs ont souvent cherché à se soigner eux-mêmes avec des médicaments sans ordonnance des VNA, car ils ont perçu les VNA comme étant facilement accessibles, fiables et bien informés, et leurs médicaments comme étant peu coûteux. Ces utilisateurs considéraient également les prestataires de soins de santé officiels comme des sources alternatives. CONCLUSIONS: Les utilisateurs qui s'approvisionnent auprès des VNA courent un risque élevé de recevoir des médicaments de qualité inférieure. La qualité des médicaments dans le système national de santé, dans la chaîne d'approvisionnement et dans le système de distribution doit être contrôlée régulièrement pour réduire l'incidence des médicaments de qualité inférieure et leur impact sur la résistance aux antimicrobiens. La lutte contre les médicaments de qualité inférieure doit intégrer une compréhension complète des facteurs socioéconomiques qui déterminent les décisions des utilisateurs concernant leur santé et le choix des prestataires de soins de santé.
Assuntos
Antibacterianos/normas , Medicamentos Falsificados , Farmácias/normas , Cromatografia Líquida , Gana , Humanos , Espectrometria de Massas em TandemRESUMO
The purpose of the study was to analyze the effectiveness of adding nebulized antibiotics to systemic antimicrobials in critically ill patients with respiratory tract infections (pneumonia or tracheobronchitis) and the effect on renal function. A retrospective observational cohort study including critically ill patients with respiratory tract infections during a 2-year period was conducted. Intervention group included patients that received nebulized and systemic antimicrobials. Patients in the control group received only systemic antimicrobials. Clinical resolution was the primary endpoint. Secondary outcomes included change in fever, inflammatory parameters, and creatinine clearance; length of hospital stay, systemic therapy, and mechanical ventilation; hospital readmission; and mortality. Regression models were performed to estimate the effect of nebulized antibiotics on outcome variables adjusted by potential confounders. A total of 136 patients were included (93 in control group and 43 in intervention group). The intervention group had higher odds of clinical resolution (adjusted odds ratio (OR): 7.1; 95% confidence interval (95% CI): 1.2, 43.3). Nebulized antibiotic therapy was independently associated with reduction in procalcitonin (adjusted OR: 12.4; 95% CI: 1.4, 109.7). There were no significant differences in the rest of the secondary outcomes or in creatinine clearance reduction. Adding nebulized antibiotics for the management of respiratory tract infections has a positive impact on clinical resolution without increasing the risk of renal toxicity.
Assuntos
Administração por Inalação , Antibacterianos/administração & dosagem , Infecções Respiratórias/tratamento farmacológico , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/normas , Peptídeo Relacionado com Gene de Calcitonina/sangue , Estado Terminal , Vias de Administração de Medicamentos , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/fisiologia , Testes de Função Renal , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Respiração Artificial , Estudos Retrospectivos , Resultado do TratamentoRESUMO
An analytical method using 2D high-performance liquid chromatography followed by tandem mass spectrometry for the quantification of the beta-lactam antibiotics amoxicillin, flucloxacillin, piperacillin, benzylpenicillin, the beta-lactamase inhibitors clavulanic acid, and tazobactam, as well as the macrolide antibiotic clindamycin, is presented. All analytes were measured in human plasma, while amoxicillin, clavulanic acid, flucloxacillin, and clindamycin were also analyzed in human tissue samples. Because of its high-protein binding, additionally, the free fraction of flucloxacillin was measured after ultrafiltration. As internal standards, deuterated forms of the beta-lactams were used. Sample preparation for all matrices was protein precipitation followed by online extraction on a TurboFlow MAX column, while sample separation was performed on an Accucore XL C18 column. Calibration curves were linear over 0.2-25 mg/kg for the tissue samples and 0.05-20 mg/l for the free fraction of flucloxacillin. In plasma, the calibration curves for amoxicillin and piperacillin were linear over 3.125-125 mg/l, for clavulanic acid and tazobactam over 1-40 mg/l, for benzylpenicillin 0.25-40 mg/l, and for flucloxacillin and clindamycin over 1.5-60 mg/l and 0.05-8 mg/l respectively. In plasma and plasma ultrafiltrate, inaccuracy and imprecision for any analyte were always less than 15%. In tissue, the accuracy and precision varied up to 16%, respectively, 20%, when various tissues were analyzed using a calibration in water. Graphical abstract.
Assuntos
Antibacterianos/análise , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Antibacterianos/sangue , Antibacterianos/normas , Cromatografia Líquida/métodos , Humanos , Padrões de Referência , Reprodutibilidade dos TestesRESUMO
An estimated 20-30% of adult women who experience an initial urinary tract infection (UTI) will have recurrent infection. In these patients, prophylaxis may be considered to improve their quality of life and control overuse of antibiotics. Despite this need, there is currently no Latin American consensus on the treatment and prophylaxis of recurrent UTIs. This consensus, signed by a panel of regional and international experts on UTI management, aims to address this need and is the first step toward a Latin American consensus on a number of urogynecological conditions. The panel agrees that antibiotics should be considered the primary treatment option for symptomatic UTI, taking into account local pathogen resistance patterns. Regarding prophylaxis, immunoactive therapy with the bacterial lysate OM-89 received a grade A recommendation and local estrogen in postmenopausal women grade B recommendation. Lower-grade recommendations include behavior modification and D-mannose; probiotics (Lactobacilli), cranberries, and hyaluronic acid (and derivatives) received limited recommendations; their use should be discussed with the patient. Though considered effective and receiving grade A recommendation, antimicrobial prophylaxis should be considered only following prophylaxis with effective non-antimicrobial measures that were not successful and chosen based on the frequency of sexual intercourse and local pathogen resistance patterns.
Assuntos
Antibacterianos/normas , Antibioticoprofilaxia/normas , Ginecologia/normas , Prevenção Secundária/normas , Infecções Urinárias/tratamento farmacológico , Adulto , Feminino , Humanos , América Latina , Recidiva , Infecções Urinárias/prevenção & controleRESUMO
The Japanese Respiratory Society 2017 guidelines strongly recommend switching from intravenous (IV) to oral antibiotics in patients with community-acquired pneumonia (CAP), following improvement in clinical symptoms and laboratory findings. Here, we retrospectively investigated the real-world, nationwide treatment and switching patterns for hospitalized patients with CAP in Japan using administrative data from 372 Japanese Diagnosis Procedure Combination hospitals from April 2010 to December 2018. Hospitalizations for CAP (patient age ≥20 years) with an A-DROP classification for CAP severity and IV antibiotics initiated on the admission date were included. Overall, 210,314 hospitalizations (moderate CAP: 61.7%) in 183,607 patients were analyzed. The median (interquartile range [IQR]) age at admission was 79 (70-86) years. Penicillin (51.9%) and cephalosporin (38.9%) were the most common IV antibiotic classes used and the median (IQR) duration of IV use was 8 (6-11) days. Switching to oral antibiotics during a hospitalization occurred in 30.1% (n = 63,311) of patients after a median (IQR) of 7 (5-10) days of IV treatment. The most frequently used oral antibiotic classes after a switch were fluoroquinolone (45.9%) and penicillin (24.8%). The switch rate was higher among hospitalizations with milder CAP, in respiratory medicine ward and in larger hospitals. The overall switch rates did not change over the study period. The findings from this analysis suggest that early switch from IV to oral antibiotics was not widely implemented during the 8 years of the study period. Further observation will be needed to see the potential impact of the guidelines update in 2017 in Japan.
Assuntos
Antibacterianos/administração & dosagem , Infecções Comunitárias Adquiridas/tratamento farmacológico , Fidelidade a Diretrizes/estatística & dados numéricos , Pneumonia Bacteriana/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Administração Intravenosa/normas , Administração Intravenosa/estatística & dados numéricos , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/normas , Cefalosporinas/administração & dosagem , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Fluoroquinolonas/administração & dosagem , Hospitalização/estatística & dados numéricos , Humanos , Japão , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Penicilinas/administração & dosagem , Pneumonia Bacteriana/microbiologia , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Estudos Retrospectivos , Índice de Gravidade de Doença , Sociedades Médicas/normas , Fatores de TempoRESUMO
Antibiotic resistance is a growing threat to global public health. The World Health Organization's Global Action Plan on Antimicrobial Resistance recommends engaging multisectoral stakeholders to tackle the issue. However, so far, few studies have addressed barriers to antibiotic development, equitable availability, and responsible antibiotic use from the perspective of stakeholders outside healthcare facilities or patient communities: the so-called third-party stakeholders. Third-party stakeholders include, inter alia, governments, regulatory agencies, and professionals working in antibiotic research and development and medical ethics. This viewpoint provides an overview of barriers to antibiotic development, equitable availability of effective antibiotics, and the responsible use of antibiotics. The barriers were identified in an exploratory, qualitative interview study with an illustrative sample of 12 third-party stakeholders. Recommendations to lift these barriers are presented, together with examples of recently-made progress. The recommendations should guide future antibiotic policies and multisectoral policy action.