Erro de administração de medicamentos anti-infeciosos por omissão de doses / Error de administración de medicamentos antiinfecciosos por omisión de dosis / Anti-infective medication administration errors by dose omission

Resumo Objetivos: Mensurar a taxa de erro de administração de medicamentos anti-infeciosos por omissão de doses em Unidade de Terapia Intensiva Adulto. Métodos: Estudo descritivo, transversal e prospectivo, realizado nos meses de outubro e novembro de 2018, em Unidade de Terapia Intensiva adulto de um Hospital de Ensino do Distrito Federal. A amostra foi por conveniência e foram registrados o número de medicamentos prescritos e o número de omissões de doses das prescrições em dois formulários. Os medicamentos foram classificados conforme o Anatomical Therapeutic Chemical Code. Realizada análise estatística com regressão logística e testes para proporções. Resultados: Coletaram-se informações de 7.140 medicamentos prescritos e foram identificadas 310 omissões de doses, correspondendo a 4,34% de taxa de erro na administração de medicamentos em geral. A amostra continha 711 anti-infeciosos (9,95%), e nestes ocorreram 48 omissões de doses, correspondendo a 6,75% de taxa de erro por omissão de doses. Entre os anti-infeciosos, o maior número de omissões foi nos carbapenêmicos (n=13; 27,08%), prescritos para serem ministrados por via intravenosa (n=38; 79,16%) e no horário das 20h (n=10; 20,83%). Conclusão: A taxa de erro de administração por omissão de dose dos anti-infeciosos foi alta, maior que entre os demais medicamentos, mais frequente pela via intravenosa e nos horários próximos às trocas de turnos. Barreiras de segurança devem ser implementadas, como a tripla checagem das doses - na farmácia, no recebimento na UTI e na administração propriamente dita, além de aprazamento adequado, educação permanente e treinamento em uso seguro de medicamentos.

Resumen Objetivos: Medir el índice de error de administración de medicamentos antiinfecciosos por omisión de dosis en Unidad de Cuidados Intensivos Adultos. Métodos: Estudio descriptivo, transversal y prospectivo, realizado en los meses de octubre y noviembre de 2018 en la Unidad de Cuidados Intensivos Adultos de un hospital universitario del Distrito Federal. La muestra fue por conveniencia y se registró la cantidad de medicamentos prescriptos y la cantidad de omisiones de dosis de las prescripciones en dos formularios. Los medicamentos se clasificaron según el Anatomical Therapeutic Chemical Code. Se realizó el análisis estadístico con regresión logística y pruebas para proporciones. Resultados: Se recolectó información de 7.140 medicamentos prescriptos y se identificaron 310 omisiones de dosis, que corresponden al 4,34% de índice de error en la administración de medicamentos en general. La muestra contenía 711 antiinfecciosos (9,95%) y ocurrieron 48 omisiones de dosis de estos medicamentos, que corresponde al 6,75% de índice de error por omisión de dosis. En los antiinfecciosos, la mayor cantidad de omisiones fue en los carbapenémicos (n=13; 27,08%), prescriptos para administrarse por vía intravenosa (n=38; 79,16%) y en el horario de las 20h (n=10; 20,83%). Conclusión: El índice de error de administración por omisión de dosis de los antiinfecciosos fue alta, mayor que entre los demás medicamentos, más frecuente por vía intravenosa y en los horarios cerca de los cambios de turno. Deben implementarse barreras de seguridad, como el triple chequeo de las dosis (en la farmacia, al recibirlo en la UCI y en la administración propiamente dicha), además de la correcta programación, educación permanente y capacitación en el uso seguro de medicamentos.

Abstract Objectives: To measure anti-infective medication administration errors by dose omission in an adult intensive care unit. Methods: A descriptive, cross-sectional, and prospective study, carried out in October and November 2018 in an adult intensive care unit of a teaching hospital in the Federal District, Brazil. The sample was one of convenience. The numbers of prescribed medications and dose omissions were registered on two forms. The medications were classified according to the Anatomical Therapeutic Chemical Code. Data were treated statistically by applying logistic regression and tests for proportions. Results: Information on about 7,140 prescribed medications was gathered, and 310 dose omissions were identified, which corresponded to a 4.34% error rate in the administration of medications in general. The sample used 711 anti-infective drugs (9.95%), which were associated with 48 dose omissions, yielding a 6.75% error rate. Among the anti-infective medications, the highest number of omissions was in the group of carbapenems (n=13; 27.08%), to be administered intravenously (n=38; 79.16%) and at 8 pm (n=10; 20.83%). Conclusion: The anti-infective medication administration error rate by dose omission was significant and higher than for the other groups of drugs, showing a higher incidence using the intravenous route and at times approaching changes of shifts. Safety barriers must be implemented, such as dose triple-checking (at the pharmacy, when the medication is received at the intensive care unit, and at the time of administration). Additionally, adequate drug scheduling, continuing education, and training programs for safe use of medications can be useful for preventing these errors.

Enterobacterias portadoras de KPC en un hospital universitario / KPC-producing Enterobacteriaceae in a university hospital

La resistencia a carbapenemes en enterobacterias representa una situación de alto impacto clínico debido a las limitadas opciones terapéuticas disponibles para el tratamiento de las infecciones causadas por estos microorganismos multirresistentes que cursan con altas tasas de morbilidad y mortalidad. En nuestro país, en los últimos 5 años, se observó la diseminación de aislamientos de Klebsiella pneumoniae portadores de carbapenemasa de tipo KPC pertenecientes al ST258, clon diseminado mundialmente. En nuestro hospital la incidencia de episodios fue aumentando, especialmente la infección del sitio quirúrgico y las bacteriemias. En el último bienio se observó la diseminación del mecanismo de resistencia a otras enterobacterias y probablemente a otros secuenciotipos de K pneumoniae con mayor sensibilidad a antibióticos no ß-lactámicos. Se hace necesario instaurar las correctas medidas de prevención y control para evitar la diseminación de estos patógenos.

The presence of carbapenem -resistant Enterobacteriaceae in clinical settings represents a concerning issue due to the limited therapeutic options available for the treatment of the infections caused by these multi-drug resistant bacteria which usually have high mortality rates. The spread of Klebsiella pneumoniae isolates belonging to ST258 was observed in the last 5 years in our country. In our hospital the number of episodes has grown with the years and the most prevalent infections were the surgical site and bacteremia. In the last 2 years KPC spread to other Enterobacteriaceae and probably to other STs in K pneumoniae which showed different susceptibility patterns to non ß-lactamic antimicrobials. We believe that it is vital to install the appropriate measures to prevent and control the dissemination of these microorganisms.

Eficacia y seguridad de ertapenem en infecciones urinarias en pediatría: revisión sistemática / Efficacy and safety of ertapenem for urinary tract infections in children: A systemic review

Introducción: Las infecciones urinarias complicadas son una causa común y potencialmente grave de morbilidad en la edad pediátrica. En los últimos años, se ha observado un incremento en la resistencia de los bacilos gram negativos a los antibióticos tanto en las infecciones urinarias intrahospitalarias como en las provenientes de la comunidad. El ertapenem es un antibiótico carbapenémico de amplio espectro, con una estructura diferente de la del resto de antibióticos ß-lactámicos que permite su administración una o dos veces por día y por vía intramuscular lo que permitiría el manejo ambulatorio de esta patología. Objetivo: evaluar la evidencia disponible sobre la eficacia y seguridad de ertapenem en infecciones urinarias en pediatría. Material y Métodos: revisión sistemática de la literatura. Se priorizó la incorporación de revisiones sistemáticas, ensayos clínicos controlados aleatorizados, y cohortes que compararan el uso de ertapenem con otros antibióticos para el tratamiento de infección urinaria complicada y cuyo punto final fuera la seguridad y/o eficacia del antibiótico. Resultados: Luego de la lectura de los resúmenes quedaron seleccionados 7 artículos de los que se dispuso del texto completo. No se encontraron revisiones sistemáticas sobre el tema. Conclusiones: La seguridad y eficacia del ertapenem fue documentada en pocos trabajos pediátricos. Se requieren más estudios de alta calidad de evidencia para recomendar el uso de ertapenem en el manejo de infecciones urinarias complicadas en pediatría. Sin embargo en casos en que sea la única opción de tratamiento ambulatorio podría considerarse su uso (AU)

Introduction: Complicated urinary infections are a common and potentially severe cause of morbidity in children. Over the past years, increased resistance of gram-negative bacilli to antibiotics has been found in both nosocomial- and communityacquired urinary infections. Ertapenem is a broad-spectrum carbapenem antibiotic with a structure different from other ß-lactam antibiotics and once- or twice-daily intramuscular administration allowing for out-patient management of the pathology. Objective: To evaluate the available evidence on efficacy and safety of ertapenem use in urinary infections in children. Material and methods: A systematic review of the literature was conducted. Systematic reviews, randomized controlled trials, and cohort studies comparing the use of ertapenem with other antibiotics for the treatment of complicated urinary infections with the endpoint of safety and/ or efficacy of the antibiotic were considered. Results: After reading the abstracts, seven studies of which the entire text was available were selected. No systemic reviews were found on the topic. Conclusions: Few studies have been published on the safety and efficacy of ertapenem in children. Further high-quality evidence studies are necessary to recommend the use of ertapenem in the management of complicated urinary infections in children. Nevertheless, in cases in which outpatient treatment is the only option the use of ertapenem may be considered (AU)

The minimal inhibitory concentration for sulbactam was not associated with the outcome of infections caused by carbapenem-resistant Acinetobacter sp. treated with ampicillin/sulbactam

OBJECTIVE: The objective of this study was to evaluate whether the outcomes of carbapenem-resistant Acinetobacter infections treated with ampicillin/sulbactam were associated with the in vitro susceptibility profiles. METHODS: Twenty-two infections were treated with ampicillin/sulbactam. The median treatment duration was 14 days (range: 3-19 days), and the median daily dose was 9 g (range: 1.5-12 g). The median time between Acinetobacter isolation and treatment was 4 days (range: 0-11 days). RESULTS: The sulbactam minimal inhibitory concentration (MIC) ranged from 2.0 to 32.0 mg/L, and the MIC was not associated with patient outcome, as 4 of 5 (80%) patients with a resistant infection (MIC≥16), 5 of 10 (50%) patients with intermediate isolates (MIC of 8) and only 1 of 7 (14%) patients with susceptible isolates (MIC ≤4) survived hospitalization. CONCLUSION: These findings highlight the need to improve the correlation between in vitro susceptibility tests and clinical outcome. .

Uso de meropenem en infecciones bacterianas complicadas / Use of meropenem in complicated bacterial infections

La selección de una terapia antimicrobiana inicial adecuada es fundamental para determinar el curso de las infecciones bacterianas severas. El surgimiento de los carbapenems, entre ellos Meropenem, como antibióticos B-lactámicos de amplio espectro, constituye una opción a considerar como terapia empírica inicial para el manejo de infecciones bacterianas severas en pacientes hospitalizados, respaldo por su eficacia terapéutica comprobada, seguridad y tolerabilidad.

Risk factors for pan-resistant Pseudomonas aeruginosa bacteremia and the adequacy of antibiotic therapy

INTRODUCTION: The aim of this study was to determine risk factors for acquiring carbapenemresistant Pseudomonas aeruginosa bacteremia (CR-PA) and factors associated with in-hospital mortality. METHODS: Seventy-seven cases of bacteremia caused by P. aeruginosa were evaluated in a hospital with high incidence of CR-PA. Clinical and laboratorial factors, and previous use of antibiotics were also evaluated. In one analysis, CR-PA and carbapenem-susceptible P. aeruginosa (CS-PA) bacteremia were compared. A second analysis compared patients who died with survivors. RESULTS: Among 77 P. aeruginosa bacteremia, 29 were caused by CR-PA. Admission to the intensive care unit, higher number of total leukocytes, and previous use of carbapenem were statistically associated with CR-PA. In the multivariate analysis, only previous use of carbapenem (including ertapenem) turned out to be a risk factor for CR-PA (p = 0.014). The 30-day mortality of patients with P. aeruginosa bloodstream infection was 44.8% for CS-PA and 54.2% for patients with CR-PA (p = 0.288). Chronic renal failure, admission to the intensive care unit, mechanical ventilation, and central venous catheter were risk factors for mortality. Incorrect treatment increased mortality of patients with bacteremia caused by CS-PA, but not for CR-SA. The odd ratio of mortality associated with incorrect therapy in patients with CS-PA was 3.30 (1.01-10.82; p = 0.043). The mortality of patients with bacteremia caused by CR-PA was unexpectedly similar regardless of antimicrobial treatment adequacy. CONCLUSION: Appropriate treatment for CS-PA bacteremia initiated within the first 24 hours was associated with lower mortality, but this cannot be extrapolated for CR-PA.

Carbapenem stewardship: positive impact on hospital ecology

INTRODUCTION: Excessive group 2 carbapenem use may result in decreased bacterial susceptibility. OBJECTIVE: We evaluated the impact of a carbapenem stewardship program, restricting imipenem and meropenem use. METHODS: Ertapenem was mandated for ESBL-producing Enterobacteriaceae infections in the absence of non-fermenting Gram-negative bacilli (GNB) from April 2006 to March 2008. Group 2 carbapenems were restricted for use against GNB infections susceptible only to carbapenems and suspected GNB infections in unstable patients. Cumulative susceptibility tests were done for nosocomial pathogens before and after restriction using Clinical and Laboratory Standards Institute (CLSI) guide-lines.Vitek System or conventional identification methods were performed and susceptibility testing done by disk diffusion according to CLSI.Antibiotic consumption (t-test) and susceptibilities (McNemar's test) were determined. RESULTS: The defined daily doses (DDD) of group 2 carbapenems declined from 61.1 to 48.7 DDD/1,000 patient-days two years after ertapenem introduction (p = 0.027). Mean ertapenem consumption after restriction was 31.5 DDD/1,000 patient-days. Following ertapenem introduction no significant susceptibility changes were noticed among Gram-positive cocci. The most prevalent GNB were P. aeruginosa, Klebsiella pneumoniae, and Acinetobacter spp. There was no change in P. aeruginosa susceptibility to carbapenems. Significantly improved P. aeruginosa and K. pneumoniae ciprofloxacin susceptibilities were observed, perhaps due to decreased group 2 carbapenem use. K. pneumoniae susceptibility to trimethoprim-sulfamethoxazole improved. CONCLUSION: Preferential use of ertapenem resulted in reduced group 2 carbapenem use, with a positive impact on P. aeruginosa and K. pneumoniae susceptibility.

Extended-spectrum beta-lactamase [ESBL] in Omani Children: Study of prevalence, risk factors and clinical outcomes at Sultan Qaboos University Hospital, Sultanate of Oman

Antimicrobial resistance is a growing problem worldwide, which imposes difficulties in the selection of appropriate empirical antimicrobial therapy. This study evaluated extended-spectrum ?-lactamase [ESBL] isolates in 2005 in The Department of Child Health at Sultan Qaboos University Hospital [SQUH], Oman. During the 12 month period from January 2005 to December 2005, ESBL isolates from paediatrics inpatients were identified and analysed. Risk factors for the patients who grew ESBLs were analysed. 13.3% of E. coli and 16.6% of Klebsiella pneumoniae isolated were ESBL producers. Most of the ESBLs were from urine [46.2%] and blood [42.6%]. The main risk factors for ESBL in these children were previous exposure to antimicrobials [100%], prolonged hospital stay, severe illness [92.3%] and female gender [84.6%]. Sensitivity of 100% was observed to carbapenems whereas 92% of the isolates were susceptible to amikacin. The oximino-cephalosporins were 100% resistant. Klebsiella pneumoniae were 100% resistant to piperacillin-tazobactam and nitrofurantoin. E. coli was 100% resistant to trimethoprim-sulfamethoxazole and ciprofloxacin. No resistance was recorded for the following combinations: amikacin plus piperacillin-tazobactam, amikacin plus nitrofurantoin and gentamicin plus nitrofurantoin. ESBL-producing organisms are becoming a major problem in Omani children. Exposure to antimicrobials and long admissions are modifiable risk factors that should be targeted for better control. Carbapenems are the most sensitive and reliable treatment options for infections caused by ESBLs. Amikacin plus piperacillin-tazobactam or nitrofurantoin are good alternatives

Seven Cases of Decreased Serum Valproic Acid Concentration During Concomitant Use of Carbapenem Antibiotics / 대한진단검사의학회지

Valproic acid (VPA) is a commonly prescribed anticonvulsant drug for the treatment of various forms of epilepsy. Concomitant administration of VPA and carbapenem antibiotics such as panipenem/ betamipron and meropenem has been reported to decrease the serum level of VPA. We observed seven cases which showed a decrease in serum levels of VPA due to concomitant use of VPA and carbapenem from January 2002 to October 2006 in a 750-bed university hospital, the average decrease of 70.4% was observed. Carbapenem antibiotics administrated concomitantly with VPA were panipenem (1 case), meropenem (3 cases), and imipenem (2 cases), and in one other case imipenem and meropenem were used sequentially. We found the VPA serum levels were significantly decreased with meropenem (n=4) more than with other carbapenem antibiotics (n=4, 89.3% vs. 51.5% decrease, P=0.03). Clinicians should be aware of this potential interaction, pay attention to the failure of seizure control due to decreased serum VPA levels with concomitant use of carbapenem antibiotics, and monitor VPA serum levels for those cases.

Antibiotics in older adults

Antibiotics are frequently prescribed in the older person, the dosification needs special care, since the pharmacokinetic parameters changes with aging and the side effects can be different in the older person. The creatinine clearance changes and we must modify the way we prescribe such antibiotics to the elderly, calculating. The variety of antibiotics now available led us to consider this paper in which we have presented the antimicrobial agents that can be considered in the treatment of the older person. We present several groups: the penicillins, cephalosporins, monobactams, carbapenems and betalactamase inhibitors or the great betalactam group. Other trimetroprin-sulfame-thoxazole, the newer macrolides (azithromycin and clarithromycin) as well as the aminoglycosides, vancomycin, clindamycin, metroridazole. The indications and contraindications are presented and reviewed.

Aspectos farmacológicos de meropenem / Pharmacological topics of meropenem

Meropenem is more stable than imipenem to renal dehydropeptidase I and can be used as a monodrug. It is bactericidal against most grampositive and gramnegative, aerobic and anaerobic species. Compared to imipenem, meropenem is more active against pseudomonas aeuginosa, burkholderia cepacia and some multiresistant nosocomial gramnegative strains because it is less inductor of extended spectrum B lactamases but may favor resistance against other antibiotic groups by an efflux pump induction. Its systemicdistribution in the extracellular space includes the central nervous system and is most excreted by glomerular filtration. As meropenem is more soluble than imipenem, it can be administered in bolus. Security profile: it rarely causes seizures, a frecuent effect observed with imipenem during tratment of bacterial meningitis in children. Other adverse reactions (local pain, pruritus and diarrhea) are as frecuent as described with imipenem