Mycobacterium abscessus keratitis after LASIK surgery / Ceratite por Mycobacterium abscessus após cirurgia LASIK

ABSTRACT A 33-year-old male presented with unilateral subacute infectious keratitis 4 weeks after surgery. Corneal inflammation was resistant to standard topical antibiotic regimens. During diagnostic flap lifting and sampling, the corneal flap melted and separated. Through flap lifting, corneal scraping, microbiological diagnosis of atypical mycobacteria, and treatment with topical fortified amikacin, clarithromycin, and systemic clarithromycin, clinical improvement was achieved.

RESUMO Paciente do sexo masculino, 33 anos, apresentou ceratite infecciosa subaguda unilateral 4 semanas após a cirurgia. A inflamação da córnea foi resistente aos regimes de antibióticos tópicos padrão. A aba da córnea foi derretida e seccionada durante o levantamento e amostragem para diagnóstico. A melhora clínica só foi alcançada após levantamento do retalho, raspagem e diagnóstico microbiológico de micobactérias atípicas e tratamento com amicacina fortificada tópica, claritromicina e claritromicina sistêmica.

Antibacterial activity of silver nanoparticles functionalized with amikacin applied against multidrug-resistant acinetobacter baumannii.

BACKGROUND: Multidrug-resistant bacteria are one of the world's biggest health problems; therefore, improving the spectrum of action of antibiotics could be necessary to reverse this situation. Amikacin and silver salts have well-known antimicrobial properties. However, both drugs lost their effectiveness against some bacteria, such as Acinetobacter baumannii. This work aims to develop a nanodrug from silver nanoparticles (AgNPs) functionalized with Amikacin against multidrug-resistant Acinetobacter baumannii. METHODS: AgNPs were produced using the bottom-up methodology and functionalized with Amikacin modified by the carbodiimide-based chemistry, forming AgNPs@Amikacin. Susceptibility tests were performed using Amikacin-resistant Acinetobacter baumannii strains to assess the bacteriostatic and bactericidal potential of the developed nanodrug. The clinical strains were induced to form a biofilm, and biomass quantification and the metabolic activity were determined. RESULTS: The AgNPs have a hydrodynamic diameter of the particles with a bimodal distribution, with a size of 37.84 nm. The FT-IR spectrum of AgNPs@Amikacin exhibits vibrational modes corresponding to Amikacin, confirming the conjugation to AgNPs. Susceptibility testing demonstrated a minimal inhibitory and bactericidal concentration of < 0.5 µg/mL. The AgNPs@Amikacin reduced the biofilm metabolic activity of Acinetobacter baumannii at rates ≥ 50%, characterized by the minimal biofilm inhibition concentrations. CONCLUSIONS: Results demonstrate a promising development of a new nanodrug with lower concentrations, less toxicity, and greater efficacy against multidrug-resistant Acinetobacter baumannii.

Aminoglycosides' dosage in hematological malignancies and febrile neutropenia: extended interval or conventional dosage?

A patient with acute myeloid leukemia presented various episodes of febrile neutropenia, for which there was no positive response to antibiotic treatments. Following an episode of bacteremia by extensively drug-resistant Klebsiella pneumoniae, amikacin was prescribed, pharmacokinetic analyses of its plasma concentrations were performed and the dosage interval was narrowed to 12 and 8 h in order to counteract the reduced postantibiotic effect due to the patient being immunocompromised. The patient responded positively, with procalcitonin decreasing and body temperature normalizing. Recovery was finally achieved, without renal or auditory damage. This case proposes tightening dosage intervals for aminoglycosides as an effective strategy in immunocompromised patients. Aminoglycosides are given over extended intervals (24 h), considering concentration-dependent effectiveness, nephrotoxicity and postantibiotic effect. Leukocytes appear to play a determining role in the postantibiotic effect, with no proposed dosing strategy for strongly immunocompromised patients.

Brazilian Butt Lift Gone Wrong: A Case Series of Non-Tuberculous Mycobacterial Gluteal Infection After Brazilian Butt Lifts.

Cosmetic surgeries are very popular and glamorized by the mainstream media and celebrities. Many individuals perceive certain bodily features as appealing for physical attraction and will attempt to obtain these features by surgery. However, these surgeries are not without risk, and significant consequences can occur if not performed by qualified medical professionals under sterile procedures. The authors present novel cases of two healthy young female patients who underwent a Brazilian butt lift (BBL) procedure a week apart by the same plastic surgeon in Mexico and developed dark painful lesions secondary to Mycobacterium abscessus (M. abscessus), a multidrug-resistant non-tuberculous mycobacterium (NTM). The literature review shows a paucity of data concerning NTM infections via surgical procedures of this type. The first case was of a 31-year-old woman who underwent a BBL and presented with bilateral dark painful buttock lesions weeks later. The patient returned to the plastic surgeon, who drained some lesions and prescribed oral antibiotics. The patient's clinical status continued to deteriorate and presented to the hospital for further assessment. The patient was initially started on broad-spectrum antibiotic therapy. The patient was found to have an HIV infection with a relatively preserved CD4 lymphocyte count and was started on antiretroviral therapy (ART). Intraoperative excisional tissue sample cultures grew M. abscessus. The patient was started on empiric tigecycline, cefoxitin, and linezolid. Preliminary culture susceptibilities showed resistance to linezolid. Linezolid was discontinued, amikacin was started, and cefoxitin and tigecycline were continued. Tigecycline, cefoxitin, and amikacin were continued and final susceptibilities showed sensitivity to the current treatment. The patient received a total of four months of treatment with tigecycline, cefoxitin, and amikacin. The second case was of a 28-year-old woman who underwent a BBL a week after the first patient by the same surgeon and developed multiple gluteal and body abscesses. The patient underwent bilateral thigh and gluteal, right chest wall, and breast surgical debridements with intraoperative cultures at a different hospital facility, which grew M. abscessus. Susceptibilities were not performed there. The patient was transferred to our facility for further care. Intraoperative cultures remained negative, and the patient was treated with a six-month course of tigecycline, cefoxitin, and amikacin.

Plan de implementación de Dosis Unitaria en el servicio de neonatología en el Hospital Cochabamba / Plan for the Implementation of the Unit Dose in the Neonatology Service of Cochabamba Hospital / Plano de Implementação de Dose Unitária no Serviço de Neonatologia do Hospital Cochabamba

En la actualidad la sepsis neonatal es uno de los principales diagnósticos en el servicio de Neonatología del Hospital Cochabamba, el medicamento de mayor elección para el tratamiento farmacológico de esta infección es la Amicacina, con la probabilidad de causar hipoacusia neonatal, la hipoacusia o disminución de la percepción auditiva, es un problema de especial importancia durante la infancia, ya que el desarrollo intelectual y social del niño está íntimamente ligado a las aferencias auditivas al sistema nervioso central, cuyo potencial discapacitante y minusvalidante depende en gran medida de la precocidad con que se realice el diagnóstico y se instaure el tratamiento y la rehabilitación. Objetivo. Diseñar un plan de implementación de Dosis Unitaria para contribuir a disminuir la hipoacusia en los pacientes neonatos. Materiales y Métodos se realizó un estudio documental basado en los registros de las Historias clínicas de los pacientes, realizándose un estudio descriptivo y retrospectivo. Se utilizaron los métodos empíricos como la encuesta, la entrevista y la observación científica, con el fin de demostrar y obtener un diagnóstico fidedigno, apoyándose con fuentes y estudios sobre la hipoacusia como sustento teórico. Resultados. Ante la evidencia de la existencia de la hipoacusia neonatal, como posible efecto adverso del uso farmacológico de la amicacina, se obtiene como resultado de la investigación la necesidad imperiosa de un plan de implementación en Dosis Unitaria para el servicio de neonatología del Hospital. Conclusiones. Los pacientes neonatos recibirán una atención segura, eficaz y humanizada con base a una implementación de Dosis Unitaria.

At present, neonatal sepsis is one of the main diagnoses in the Neonatology service of the Cochabamba Hospital, the drug of choice for the pharmacological treatment of this infection is Amicacin, with the probability of causing neonatal hypoacusis, the hypoacusis or decrease in auditory perception, is a problem of special importance during childhood, since the intellectual and social development of the child is intimately linked to the auditory afferents to the central nervous system, whose disabling and handicapping potential depends to a great extent on the precocity with which the diagnosis is made and the treatment and rehabilitation are established. Objective. To design a plan for the implementation of Unit Dose to contribute to the reduction of hearing loss in neonatal patients. Materials and Methods. A documentary study was carried out based on the patients' medical records, performing a descriptive and retrospective study. Empirical methods such as survey, interview and scientific observation were used in order to demonstrate and obtain a reliable diagnosis, supported by sources and studies on hypoacusis as theoretical support. Results. In view of the evidence of the existence of neonatal hypoacusis, as a possible adverse effect of the pharmacological use of amikacin, it is obtained as a result of the research the imperative need of an implementation plan in Unit Dose for the neonatology service of the Hospital. Conclusions. Neonatal patients will receive safe, effective and humanized care based on a Unit Dose implementation.

Atualmente, a sepse neonatal é um dos principais diagnósticos no serviço de Neonatologia do Hospital de Cochabamba. O medicamento de escolha para o tratamento farmacológico desta infecção é a Amicacina, com a probabilidade de causar hipoacusia neonatal, hipoacusia ou diminuição da percepção auditiva, é um problema de especial importância durante a infância, já que o desenvolvimento intelectual e social da criança está intimamente ligado aos aferentes auditivos do sistema nervoso central, cujo potencial incapacitante e deficiente depende em grande parte de quão cedo o diagnóstico é feito e como o tratamento e a reabilitação são estabelecidos. Objetivo. Elaborar um plano para a implementação da Unidade Dose para contribuir para a redução da perda auditiva em pacientes neonatais. Materiais e Métodos. Foi realizado um estudo documental baseado nos registros das histórias clínicas dos pacientes, realizando um estudo descritivo e retrospectivo. Métodos empíricos como pesquisa, entrevista e observação científica foram utilizados para demonstrar e obter um diagnóstico confiável, apoiado por fontes e estudos sobre hipoacusia como suporte teórico. Resultados. Dada a evidência da existência de hipoacusia neonatal, como um possível efeito adverso do uso farmacológico do amikacin, os resultados da pesquisa mostram a necessidade imperativa de um plano de implementação na Unidade Dose para o serviço de neonatologia do Hospital. Conclusões. Os pacientes neonatais receberão um cuidado seguro, eficaz e humanizado com base na implementação de uma dose unitária.

Protective effect of creatine on amikacin-induced ototoxicity / Efeito protetor da creatina na ototoxicidade induzida por amicacina

Abstract Introduction Aminoglycosides are widely known for their ototoxic side effects. Nevertheless, they are potent antibiotics used in the treatment of life-threatening conditions because of the current concern for antibiotic resistance. We hypothesized that creatine supplements which are believed to improve mitochondrial antioxidant defense system and maintain optimal energy homeostasis may improve the ototoxic side effects. Objective This study aimed to investigate the protective effects of creatine monohydrate against ototoxicity induced by amikacin in rats in an experimental animal model, using distortion product otoacoustic emissions and auditory brainstem response. Methods Twenty healthy rats were assigned to four groups (5 rats in each): the control group, the creatine monohydrate group, the amikacin group and the amikacin + creatine monohydrate group. The creatine monohydrate group received creatine at a dose of 2 g/kg once daily via gastric gavage for 21 days. The amikacin group received amikacin at a dose of 600 mg/kg by intramuscular injections once daily for 21 days. The amikacin + creatine monohydrate group received intramuscular injections of amikacin (600 mg/kg) once daily for 21 days and creatine monohydrate (2 g/kg) once daily via gastric gavage for 21 days. The control group received nothing. The distortion product otoacoustic emissions and auditory brainstem response measurements were performed on all rats on days 0, 7, 21. Results Regarding auditory brainstem response values, a significant increase in the auditory threshold was observed in the amikacin group on day 21 (p < 0.001). The amikacin+creatine monohydrate group showed significantly lower levels of auditory brainstem response auditory thresholds on day 21 in comparison to the amikacin group (p < 0.001). Additionally, the control group and the amikacin+creatine monohydrate group did not differ significantly with respect to auditory brainstem response thresholds on treatment day 21 (p > 0.05). When we compare distortion product otoacoustic emissions values, there was no significant difference between the amikacin and amikacin+creatine monohydrate groups on day 7 (p > 0.05), However significantly greater distortion product otoacoustic emissions values were observed in the amikacin+creatine monohydrate group on day 21 compared to the amikacin group (p < 0.001). Conclusion Our findings demonstrate that creatine treatment protects against amikacin ototoxicity when given at a sufficient dose and for an adequate time period.

Resumo Introdução Os aminoglicosídeos são amplamente conhecidos por seus efeitos colaterais ototóxicos. No entanto, eles são antibióticos potentes usados no tratamento de doenças potencialmente fatais devido à atual preocupação com a resistência aos antimicrobianos. Nossa hipótese é que os suplementos de creatina, aos quais atribui-se um efeito benéfico sobre o sistema de defesa antioxidante mitocondrial e manutenção da homeostase energética ideal, possam melhorar os efeitos colaterais ototóxicos. Objetivo Investigar os efeitos protetores da creatina mono-hidratada contra a ototoxicidade induzida pela amicacina em ratos em um modelo experimental animal com o uso das emissões otoacústicas por produto de distorção e o potencial evocado auditivo de tronco encefálico. Método Vinte ratos saudáveis foram divididos em quatro grupos (5 ratos em cada): o grupo controle, o grupo creatina mono-hidratada, o grupo amicacina e o grupo amicacina + creatina mono-hidratada. O grupo creatina mono-hidratada recebeu creatina na dose de 2 g / kg uma vez ao dia por gavagem gástrica por 21 dias. O grupo amicacina recebeu amicacina na dose de 600 mg/kg por injeção intramuscular uma vez ao dia por 21 dias. O grupo amicacina + creatina mono-hidratada recebeu injeções intramusculares de amicacina (600 mg/kg) uma vez ao dia por 21 dias e creatina mono-hidratada (2 g/kg) uma vez ao dia por gavagem gástrica por 21 dias. O grupo controle nada recebeu. As medidas de emissões otoacústicas por produto de distorção e potencial evocado auditivo de tronco encefálico foram feitas em todos os ratos nos dias 0, 7, e 21. Resultados Em relação aos valores do potencial evocado auditivo de tronco encefálico, foi observado aumento significante dos limiares auditivos no grupo amicacina no 21° dia (p < 0,001). O grupo amicacina + creatina mono-hidratada apresentou níveis significantemente mais baixos de limiares auditivos de potencial evocado auditivo de tronco encefálico no dia 21 em comparação com o grupo amicacina (p < 0,001). Além disso, o grupo controle e o grupo amicacina + creatina mono-hidratada não diferiram significantemente em relação aos limiares de potencial evocado auditivo de tronco encefálico no 21° dia de tratamento (p > 0,05). Quando comparamos os valores de emissões otoacústicas por produto de distorção, não houve diferença significante entre os grupos amicacina e amicacina + creatina mono-hidratada no 7° dia (p > 0,05). No entanto, valores significantemente mais altos de emissões otoacústicas por produto de distorção foram observados no grupo amicacina + creatina mono-hidratada no 21° dia em comparação com o grupo amicacina p < 0,001). Conclusão O tratamento com creatina mono-hidratada protege contra a ototoxicidade da amicacina quando administrado em dose suficiente e por um período de tempo adequado.

Protective effect of creatine on amikacin-induced ototoxicity.

INTRODUCTION: Aminoglycosides are widely known for their ototoxic side effects. Nevertheless, they are potent antibiotics used in the treatment of life-threatening conditions because of the current concern for antibiotic resistance. We hypothesized that creatine supplements which are believed to improve mitochondrial antioxidant defense system and maintain optimal energy homeostasis may improve the ototoxic side effects. OBJECTIVE: This study aimed to investigate the protective effects of creatine monohydrate against ototoxicity induced by amikacin in rats in an experimental animal model, using distortion product otoacoustic emissions and auditory brainstem response. METHODS: Twenty healthy rats were assigned to four groups (5 rats in each): the control group, the creatine monohydrate group, the amikacin group and the amikacin+creatine monohydrate group. The creatine monohydrate group received creatine at a dose of 2g/kg once daily via gastric gavage for 21 days. The amikacin group received amikacin at a dose of 600mg/kg by intramuscular injections once daily for 21 days. The amikacin+creatine monohydrate group received intramuscular injections of amikacin (600mg/kg) once daily for 21 days and creatine monohydrate (2g/kg) once daily via gastric gavage for 21 days. The control group received nothing. The distortion product otoacoustic emissions and auditory brainstem response measurements were performed on all rats on days 0, 7, 21. RESULTS: Regarding auditory brainstem response values, a significant increase in the auditory threshold was observed in the amikacin group on day 21 (p< 0.001). The amikacin+creatine monohydrate group showed significantly lower levels of auditory brainstem response auditory thresholds on day 21 in comparison to the amikacin group (p< 0.001). Additionally, the control group and the amikacin+creatine monohydrate group did not differ significantly with respect to auditory brainstem response thresholds on treatment day 21 (p> 0.05). When we compare distortion product otoacoustic emissions values, there was no significant difference between the amikacin and amikacin+creatine monohydrate groups on day 7 (p> 0.05), However significantly greater distortion product otoacoustic emissions values were observed in the amikacin+creatine monohydrate group on day 21 compared to the amikacin group (p< 0.001). CONCLUSION: Our findings demonstrate that creatine treatment protects against amikacin ototoxicity when given at a sufficient dose and for an adequate time period.

Antibiotic susceptibility patterns of bacterial isolates of patients with upper respiratory tract infections

Abstract To evaluate the antibiotic susceptibility patterns in URTIs reporting to tertiary hospitals of Lahore. A cross-sectional study employing 259 culture sensitivity reports obtained from tertiary care hospitals of Lahore. Using SPSS, descriptive statistics were used to estimate frequencies and percentages. In URTIs, S. aureus (5%) was the frequent gram-positive isolate followed by MRSA (1.5%) and MSSA (1.5%), while P. aeruginosa (15.8%) was the prevalent gram-negative isolate followed by Klebsiella (13.1%) and E. coli (6.9%). Against P. aeruginosa, ceftazidime (7.7%), cefuroxime/ceftriaxone (4.6%), amoxicillin (4.3%) and ciprofloxacin (4.2%), were tested resistant, while imipenem (11.2%), ciprofloxacin (9.2%), amikacin (9.2%), meropenem/ levofloxacin/gentamicin (8.1%) and piptaz (6.9%) were found sensitive. Against Klebsiella, carbepenems (7.3%), amikacin (6.5%), ciprofloxacin (5.4%) and gentamicin (5%) were tested sensitive, whereas, ceftazidime (8.5%), ceftriaxone (5.8%), cefaclor (5.5%), ampicillin (4.6%), co-amoxiclave (4.2%) and ciftazidime/ciprofloxacin (3.8%) were found resistant. Overall, imipenem (35%), meropenem (30.8%) and amikacin (31.9%) were the three most sensitive antibiotics, while ceftazidime (25.4%), ceftriaxone (19.2%) and ampicillin (18.5%) were the three most resistant antibiotics. Data suggested that P.aeruginosa and Klebsiella, were the most frequent bacterial isolates in URTIs of Lahore. These isolates were resistant to ampicillin, cefuroxime and ceftazidime, but were sensitive to carbapenem and aminoglycosides

Pharmacokinetics of Intraperitoneal Vancomycin and Amikacin in Automated Peritoneal Dialysis Patients With Peritonitis.

Objective: The study aimed to evaluate the vancomycin and amikacin concentrations in serum and dialysate for automatic peritoneal dialysis (APD) patients. Methods: A total of 558 serum and dialysate samples of 12 episodes of gram-positive and 18 episodes of gram-negative peritonitis were included to investigate the relationship between vancomycin and amikacin concentrations in serum and dialysate on the first and third days of treatment. Samples were analysed 30, 120 min, and 48 h after intraperitoneal administration of vancomycin in peritonitis caused by gram-positive agents and 30, 120 min, and 24 h after intraperitoneal administration of amikacin in peritonitis caused by gram-negative agents. Vancomycin was administered every 72 h and amikacin once a day. The target therapeutic concentration of amikacin was 25-35 mg/l at the peak moment and 4-8 mg/l at the trough moment; and after 48 h for vancomycin, 15-20 mg/l at the trough moment. Results: For peritonitis caused by gram-negative agents, at the peak moment, therapeutic levels of amikacin were reached in dialysate in 80.7% of patients with evolution to cure and in 50% of patients evaluated as non-cure (p = 0.05). At the trough moment, only 38% were in therapeutic concentrations in the dialysate in the cure group and 42.8% in the non-cure group (p = 1). Peak plasma concentrations were subtherapeutic in 98.4% of the samples in the cure group and in 100% of the non-cure group. At the trough moment, therapeutic concentrations were present in 74.4% of the cure group and 71.4% of the non-cure group (p = 1). Regarding vancomycin and among gram-positive agents, therapeutic levels were reached at the peak moment in 94% of the cure group and 6% of the non-cure group (p = 0.007). After 48 h, 56.8% of the cure group had a therapeutic serum concentration whereas for the non-cure group it was only 33.3% (p = 0.39). Conclusion: Despite a small sample size, we demonstrated peak dialysate amikacin level and peak serum vancomycin level correlates well with Gram-negative and Gram positve peritonitis cure, respectively. It is suggested to study the antibiotics pharmacodynamics for a better understanding of therapeutic success in a larger sample.

Amikacin for the treatment of carbapenem-resistant Klebsiella pneumoniae infections: clinical efficacy and toxicity.

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients' 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 µg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P < 0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P < 0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.

Impacto del monitoreo terapéutico de vancomicina y amikacina en la optimización de dosis de antimicrobianos en pacientes pediátricos / Impact of the vancomycin and amikacin therapeutic monitoring in the optimization of antimicrobial dose in pediatric patients

INTRODUCCIÓN: La monitorización de antimicrobianos mediante sus concentraciones plasmáticas permite determinar la posología óptima de éstos, conducta esencial en pediatría. OBJETIVOS: Describir la monitorización de concentraciones plasmáticas de antimicrobianos y el ajuste de dosis en población pediátrica para determinar si las dosis utilizadas alcanzan rangos terapéuticos. PACIENTES Y MÉTODOS: Estudio descriptivo, retrospectivo, utilizando una base de datos con medición de concentraciones plasmáticas de amikacina y vancomicina en pacientes pediátricos del Hospital San Borja Arriarán, entre 2015-2018. Se determinó el número de pacientes que alcanzó rango terapéutico con dosis inicial, cuántos requirieron ajuste y sus características. RESULTADOS: Se monitorizó 104 concentraciones totales. Para vancomicina 65 concentraciones plasmáticas eran basales encontrándose fuera de rango terapéutico 56,5%; de los que requirieron ajuste, 25% fueron neonatos con mayor probabilidad de estar fuera de rango versus otros (p = 0,022). Para amikacina la Cpeak estuvo en rango en 60% de mediciones; 15,4% requirió ajuste incluyendo pacientes con fibrosis quística y oncológicos. No fue necesario efectuar ajustes en pacientes sin co-morbilidad. CONCLUSIÓN: La medición de concentraciones plasmáticas es necesaria para ajustar de forma individualizada la dosis, especialmente en pacientes pediátricos con fibrosis quística, oncológicos y en neonatología, donde es más probable no alcanzar rango terapéutico con las dosis iniciales.

BACKGROUND: The monitoring of antimicrobial therapy through plasma levels makes it possible to determine the optimal dosage of antimicrobials, an essential approach in pediatrics. AIM: To describe the monitoring of plasma antimicrobial levels and dose adjustment in the pediatric population to determine if the doses used reach therapeutic ranges. METHODS: Retrospective, descriptive study using a database with measurement of plasma levels of amikacin and vancomycin in pediatric patients at San Borja Arriarán Hospital between 2015-2018. The number of patients who reached the therapeutic range with the initial dose, how many required adjustment and their characteristics were determined. RESULTS: 104 total levels were monitored. For vancomycin 65 plasmatic levels were baseline, being outside the therapeutic range 56.5%; 25% of those requiring adjustment were neonates with a higher probability of being out of range versus others (p = 0.022). For amikacin, Cpeak was in range in 60% of measurements; 15.4% required adjustment, including patients with cystic fibrosis and cancer, without adjustments in patients without comorbidity. CONCLUSION: Measurement of plasma levels is necessary to individually adjust the dose, especially in pediatric patients with cystic fibrosis, oncology and in neonatology where it is more likely not to reach a therapeutic range with initial doses.

Distribution of genes encoding 16S rRNA methyltransferase in plazomicin-nonsusceptible carbapenemase-producing Enterobacterales in Brazil.

BACKGROUND: The presence of 16S rRNA methyltranferases (16S-RMTases) in carbapenemase-producing Enterobacterales (CPE) is a major concern because it inactivates all clinical use of aminoglycosides, including plazomicin. The aim of this study is to investigate the prevalence of 16S-RMTases in CPE nonsusceptible to plazomicin collected in different Brazilian hospitals. METHODS: All isolates with plazomicin MIC ≥ 4 µg/mL (n = 67) were screened for the presence of 16S-RMTases by sequencing. RESULTS: 54 (80.6%) isolates encoded 16S-RMTase genes (41 rmtB1, 7 armA, 3 rmtD2, 1 rmtD1 and 2 rmtC). Among 41 samples rmtB1 positive, 40 co-harbored blaKPC-2 and 1 blaOXA-48 gene. Of the seven isolates harboring armA gene, 6 were New Delhi Metallo-beta-lactamase (NDM)-producer. rmtD was only found in isolates Klebsiella pneumoniae Carbapenemase (KPC)-producers, one in Serratia marcescens with rmtD2, not reported in Brazil. CONCLUSION: The co-existence of 16S-RMTase and CPE is worrisome because of limited treatment options and the endemic characteristic of (KPC) and NDM in Brazil.

In vitro activity of polymyxin B in combination with meropenem, amikacin and gentamicin against Klebsiella pneumoniae clinical isolates co-harbouring aminoglycoside-modifying enzymes, blaNDM-1 and blaKPC-2.

OBJECTIVES: Multidrug-resistant Klebsiella pneumoniae carrying blaNDM-1 and blaKPC-2 genes are a worldwide concern for which combination antimicrobial therapy may be the only viable option. The aim of this study was to investigate the in vitro activity of combinations of polymyxin B (PMB) with meropenem (MEM), amikacin (AMK) and gentamicin (GEN) at subinhibitory concentrations against two K. pneumoniae clinical isolates co-harbouring blaNDM-1, blaKPC-2 and aminoglycoside-modifying enzymes and resistant to PMB. METHODS: Synergy and bactericidal activity were evaluated by chequerboard and time-kill assays against two PMB-resistantK. pneumoniae clinical isolates carrying the blaNDM-1, blaKPC-2, aac(3)-IIa, aac(6')-Ib, aph(3')-VI and ant(2'')-Ia genes. Five combinations of PMB, MEM, AMK and GEN were evaluated. RESULTS: The PMB/MEM and PMB/AMK combinations proved to be the best options against isolate K7R2, mainly because they demonstrated bactericidal activity when using subinhibitory concentrations of these antimicrobials. However, none of the studied combinations was bactericidal against isolate K11R2. CONCLUSION: The combinations used in this study showed synergy against NDM-and KPC-producing isolates but, given their bactericidal activity, the combinations of PMB/MEM and PMB/AMK were the most active against one isolate. It can also be concluded that the antimicrobials to which the bacteria were resistant could form part of combination therapy.

Dried plasma spots for therapeutic monitoring of amikacin: Validation of an UHPLC-MS/MS assay and pharmacokinetic application.

Amikacin (AMI) is an aminoglycoside antibiotic widely used in the treatment of severe infections caused by multi-resistant bacteria, with established exposition targets in therapeutic drug monitoring (TDM). The usual specimen for AMI concentration measurement is plasma or serum. The access to TDM of AMI in Developing Countries is constrained by the limited availability of laboratories performing the quantitation of this drug. In this context, the use of dried microsamples, such as dried plasma spots (DPS) could be an alternative to allow reduced specimen transportation and storage costs in resource-limited settings, increasing the access to TDM of AMI. This study aimed to develop and validate the first report of simultaneous determination of AMI and creatinine (CRE) in DPS, using UHPLC-MS/MS. Precision, accuracy and stability assays showed acceptable results. AMI was stable in DPS for 14 days at 6 °C, 2 days at 22 °C, and one day at 42 °C. CRE was stable during 14 days at all tested temperatures. AMI and CRE concentrations in DPS and plasma were compared by Passing-Bablok regression and Bland and Altmann plots and presented comparable results. Estimates of patient's clearance, volume of distribution and suggested doses of AMI were also similar using DPS or plasma concentrations. The assay provides a useful logistic alternative to allow more widespread access to dose individualization of AMI in limited resources settings.

Population Pharmacokinetics of Amikacin Administered Once Daily in Patients with Different Renal Functions.

The aim of this work was to evaluate the pharmacokinetics of amikacin in Mexican patients with different renal functions receiving once-daily dosing regimens and the influence of clinical and demographical covariates that may influence the optimization of this antibiotic. A prospective study was performed in a total of 63 patients with at least one determination of amikacin plasma concentration. Population pharmacokinetic (PK) parameters were estimated by nonlinear mixed-effects modeling; validations were performed for dosing recommendation purposes based on PK/pharmacodynamic simulations. The concentration-versus-time data were best described by a one-compartment open model with proportional interindividual variability associated with amikacin clearance (CL) and volume of distribution (V); residual error followed a homoscedastic trend. Creatinine clearance (CLCR) and ideal body weight (IBW) demonstrated significant influence on amikacin CL and V, respectively. The final model [CL (liters/h) = 7.1 × (CLCR/130)0.84 and V (liters) = 20.3 × (IBW/68)2.9] showed a mean prediction error of 0.11 mg/liter (95% confidence interval, -3.34, 3.55) in the validation performed in a different group of patients with similar characteristics. There is a wide variability in amikacin PK parameters in Mexican patients. This leads to inadequate dosing regimens, especially in patients with augmented renal clearance (CLCR of >130 ml/min). Optimization based on the final population PK model in Mexican patients may be useful, since reliability and clinical applicability have been demonstrated in this study.

Antimicrobial therapy with aminoglycoside or meropenem in the intensive care unit for hospital associated infections and risk factors for acute kidney injury.

There have historically been concerns of acute kidney injury (AKI) with the use of aminoglycosides. The present study aimed to compare the AKI incidence and mortality rate between critically ill patients treated with aminoglycoside or meropenem in the intensive care unit setting using a propensity score matching approach. This cross-sectional study was conducted at two university hospitals from January 2011 to October 2017. Clinical and laboratorial data were evaluated to exclude potential confounders and to calculate the Charlson index. AKI was classified according to the Acute Kidney Injury Network criteria. All tests were two-tailed, and a p value ≤ 0.05 was considered significant in the univariate and multivariate analyses. We included 494 patients, 95 and 399 of whom used meropenem and aminoglycoside, respectively. Patients in the subgroup that used meropenem were matched with controls (aminoglycoside). Among the 494 patients, 120 developed any grade of AKI (24.2%). After propensity score matching, there were no significant differences in AKI incidence and mortality rate between the aminoglycoside and meropenem groups (p = 0.324 and 0.464, respectively). Patients on the aminoglycoside regimen neither presented a higher AKI incidence nor mortality rate when compared with those on the meropenem regimen. Aminoglycosides may be a safe option for the treatment of critically ill patients on carbapenem sparing antimicrobial stewardship programs.

Prevalence of Klebsiella pneumoniae carbapenemase - and New Delhi metallo-beta-lactamase-positive K. pneumoniae in Sergipe, Brazil, and combination therapy as a potential treatment option

Abstract INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae infection lacks treatment options and is associated with prolonged hospital stays and high mortality rates. The production of carbapenemases is one of the most important factors responsible for this multi-resistance phenomenon. METHODS: In the present study, we analyzed the presence of genes encoding carbapenemases in K. pneumoniae isolates circulating in one of the public hospitals in the city of Aracaju, Sergipe, Brazil. We also determined the best combination of drugs that display in vitro antimicrobial synergy. First, 147 carbapenem-resistant K. pneumoniae isolates were validated for the presence of blaKPC, bla GES, bla NDM, bla SPM, bla IMP, bla VIM, and bla OXA-48 genes using multiplex polymerase chain reaction. Thereafter, using two isolates (97 and 102), the role of double and triple combinational drug therapy as a treatment option was analyzed. RESULTS: Seventy-four (50.3%) isolates were positive for bla NDM, eight (5.4%) for bla KPC, and one (1.2%) for both bla NDM and bla KPC. In the synergy tests, double combinations were better than triple combinations. Polymyxin B and amikacin for isolate 97 and polymyxin B coupled with meropenem for isolate 102 showed the best response. CONCLUSIONS: Clinicians in normal practice use multiple drugs to treat infections caused by multi-resistant microorganism; however, in most cases, the benefit of the combinations is unknown. In vitro synergistic tests, such as those described herein, are important as they might help select an appropriate multi-drug antibiotic therapy and a correct dosage, ultimately reducing toxicities and the development of antibiotic resistance.

Impacto en el consumo de amikacina y ceftriaxone en una unidad de emergencias de adultos, luego de la implementación de una guía para el tratamiento de la infección urinaria alta / Impact on the consumption of ceftriaxone and amikacin in an adult emergency unit, after the implementation of a guide for the treatment of pyelonephritis

Introducción: los programas de optimización del uso de antimicrobianos son fundamentales para mejorar los resultados clínicos de los pacientes. Objetivos: determinar el impacto en el consumo de amikacina y ceftriaxona, además de cambios de sensibilidad de las principales bacterias en la unidad de emergencias del hospital Carlos van Buren de Valparaíso, Chile, luego de la implementación de una guía para el tratamiento de la ITU alta. Materiales y método: estudio cuasi-experimental antes/después. Se implementó una guía de tratamiento para la ITU alta, la cual fue enviada vía WhatsApp a los médicos de la unidad. Luego se midieron las dosis diarias definidas (DDD) de amikacina y ceftriaxona y se compararon con las DDD de los mismos meses del año anterior. Además se extrajo la sensibilidad de E.coli, K. pneumonia y P.mirabilis aisladas de urocultivos. Resultados: posterior a la intervención hubo un aumento de las DDD de amikacina y una disminución de las de ceftriaxona. K.pneumoniae mantuvo su sensibilidad a amikacina y la aumentó para cefotaxima, ertapenem y meropenem. Conclusiones: la implementación de una guía de tratamiento de la ITU alta aumentó el consumo de amikacina y disminuyó el de ceftriaxona. K.pneumoniae aumentó su sensibilidad a cefotaxima, ertapenem y meropenem.

Introduction: different antimicrobial stewardship programs are fundamental to improve clinical results in patients. Objectives: to determine the impact on amikacin and ceftriaxone consumption, in addition to knowing changes in sensitivity of the main agents in the emergency unit of the Carlos van Buren Hospital in Valparaíso, Chile, after the implementation of a treatment guide for pyelonephritis. Materials and methods: quasi-experimental before/after study. A treatment guide was implemented for pyelonephritis. The guide was sent by WhatsApp to all clinicians in the emergency unit. Following the intervention, amikacin and ceftriaxone defined daily dose (DDD) were measured and compared with the DDD for the same months of the previous year. In addition, the sensitivity of E.coli, K. pneumonia and P.mirabilis isolated from urine cultures was extracted. Results: after the intervention there was a sustained increase of the DDD of amikacin and a decrease in the DDD of ceftriaxone in the months studied period. K. pneumoniae maintained its sensitivity to amikacin and increased it to cefotaxime, ertapenem, and meropenem. Conclusions: The guide's implementation for treatment of high UTI in the emergency unit of the Carlos van Buren hospital increased the consumption of amikacin and decreased that of ceftriaxone. K. pneumoniae increased its sensitivity to cefotaxime, ertapenem and meropenem.

Piperacillin/tazobactam plus amikacin vs. piperacilin/tazobactam: treatment for children with febrile neutropenia / Piperacilina/tazobactam más amikacina vs. piperacilina/tazobactam: tratamiento en niños con neutropenia febril

Background: Pediatric patients with febrile neutropenia usually receive a combination of broad spectrum antimicrobials. Treatment without aminoglycoside seems to have advantages. Objective: To compare the efficacy of piperacillin/tazobactam plus amikacin versus piperacillin/tazobactam. Methods: Randomized, open label, controlled clinical trial. Sample size for an efficacy of 55%, and delta of 25%; 80 episodes were required for each group. Selection criteria were patients with febrile neutropenia, candidates to receive parenteral antimicrobial treatment; they were randomized to one of two groups, piperacillin/tazobactam plus amikacin (Group A), or piperacillin/tazobactam (Group B). The outcomes were failure, adverse events and death. Mantel-Haenszel chi squaretest and exact Fisher test were used. Reduction of relative and absolute risk (RRR and ARR), 95% confidence intervals (CI 95%) and number needed to treat (NNT) were calculated. Results: 88 Episodes were analyzed in group A and 76 in group B. There was no statistical difference in general characteristics of patients or type of infections. There was not significant statistical difference in: failure 31.8% group A, 30.2% group B (RR 1.05, CI 95% 0.66-1.66, p = 0.86), or adverse events (one in each group). The RRR was 1.5%, and ARR 2%, with a NNT of 67. Conclusion: Piperacillin/tazobactam without amikacin was as effective as combination therapy in pediatric patients with febrile neutropenia.

Introducción: los pacientes pediátricos con neutropenia febril habitualmente reciben una combinación de antimicrobianos de amplio espectro. La terapia sin aminoglucósido parece tener ventajas. Objetivo: comparar la eficacia de piperacilina/tazobactam más amikacina frente a la de piperacilina/tazobactam. Métodos: ensayo clínico controlado aleatorizado. Tamaño de muestra para una eficacia de 55%, y delta de 25%; se calcularon 80 episodios por grupo. Fueron seleccionados pacientes con neutropenia febril, candidatos a recibir antimicrobiano parenteral; se aleatorizaron a recibir piperacilina/tazobactam más amikacina (grupo A) o piperacilina/tazobactam (grupo B). Los desenlaces fueron falla, eventos adversos y muerte. Se emplearon las pruebas Chi cuadrada de Mantel-Haenszel y exacta de Fisher. Se calculó la reducción de riesgo relativo y absoluto (RRR y RRA), intervalos de confianza 95% (IC 95%) y número necesario a tratar (NNT). Resultados: se analizaron 88 episodios en el grupo A y 76 en el grupo B. No hubo diferencias estadísticas en características generales ni en el tipo de infecciones. No se encontró diferencia significativa en: falla 31.8% grupo A, 30.2% grupo B (RR 1.05, IC 95% 0.66-1.66, p = 0.86), ni en los eventos adversos (uno en cada grupo). La RRR fue de 1.5%, RRA de 2%, con un NNT de 67. Conclusión: la terapia con piperacilina/tazobactam sin amikacina fue tan efectiva como la terapia combinada para pacientes pediátricos con neutropenia febril.

Population pharmacokinetics of amikacin in patients with pediatric cystic fibrosis.

INTRODUCTION: Amikacin is commonly used in patients with pediatric cystic fibrosis (CF) for the treatment of pulmonary exacerbations. Amikacin efficacy is related to maximum plasma concentration/minimum inhibitory concentration (Cmax/MIC) ratio >8. Pharmacokinetic data in patients with pediatric CF are scarce. The aim of this study was to develop a population pharmacokinetic (PopPK) model describing amikacin disposition in patients with pediatric CF. METHODS: CF patients under 18 years of age with pulmonary exacerbation who received amikacin were enrolled. Patients received different amikacin regimens (30 mg-1 kg-1 day-1 every 8, 12, or 24 hours) depending on the patient's status and hospital protocols. Amikacin serum levels were obtained for therapeutic drug monitoring. PopPK model was developed using MONOLIX Suite-2018R1 (Lixoft). RESULTS: A total of 39 patients (114 amikacin concentrations) were included in this study. Population estimates for the elimination rate constant (k) and the volume of distribution (V) were 0.541 hours-1 and 0.451 L/kg, respectively. Between-subject and between-occasion variability were 53% and 16.5% for k and 31% and 22% for V, respectively. Bodyweight was a significant covariate associated with V. Based on simulations, almost 70% of the patients receiving 30 mg-1 kg-1 day-1 every 24 hours would achieve a Cmax/MIC ratio >8 which is an appropriate therapeutic goal while no patient in the other two groups (Q8 and Q12) would achieve that objective. CONCLUSIONS: The regimen of 30 mg-1 kg-1 day-1 every 24 hours more adequately fulfilled the therapeutic target for amikacin. Although all our patients had good clinical results and a good adverse-events profile, further studies are necessary to redefine the optimal treatment strategy.