Diabetes as a risk factor of acute kidney injury in vancomycin users: an observational and prospective study

Diabetes was investigated as a risk factor for nephrotoxicity induced by vancomycin. In the present study, the drug's nephrotoxic effect was indirectly evaluated by Glomerular Filtration Rate, albuminuria and serum levels of creatinine and urea on the 1st, 7th and 14th days of vancomicyn therapy in a group of diabetic and non-diabetic patients, with and without previous nephropathy. The correlations between investigated variables (including the population's epidemiological profile and hospital care) were measured by the Spearman test. The sample consisted of 132 patients, predominantly male diabetic patients with previous nephropathy, over 40 years, receiving ≥ 10 grams of vancomycin for the treatment of infectious diseases and showing satisfactory clinical outcomes. A risk of vancomycin drug interaction with potential nephrotoxic outcome was observed in 36.4% of patients who used multiple drugs. Furthermore, 80% of patients had an increase of at least 0.5 mg.dL-1 in baseline serum levels of creatinine and urea at the end of the study. This was more common among the diabetic patients with previous nephropathy, showing higher albuminuria and a reduction in the Glomerular Filtration Rate. Therefore, it has been recommended that the use of vancomycin in diabetic patients should be in careful dosages and that kidney functioning be monitored.

Drug-related problems in cardiac neonates under intensive care / Problemas relacionados a medicamentos em neonatos cardiopatas sob terapia intensiva

ABSTRACT Objective: To determine the frequency and nature of the Drug Related Problems (DRP) in neonates with cardiac diseases admitted to an Intensive Care Unit. Methods: This prospective cross-sectional study was developed at the Neonatal Intensive Care Unit (NICU) of a teaching maternity hospital in Brazil from January 2014 to December 2016. All neonates diagnosed with any heart disease (congenital heart disease, cardiomyopathy, arrhythmias, etc.) and who were admitted to the NICU for more than 24 hours with at least one prescribed drug were included in the study. Demographic and clinical data were collected from the records of the institution's clinical pharmacy service. DRP and their respective interventions were independently reviewed and classified by two pharmacists. DRP classification was performed through the Pharmaceutical Care Network Europe v6.2 system. Results: 122 neonates were included in the study. The frequency of neonates exposed to DRP was 76.4% (confidence interval of 95% [95%CI] 65.9-82.0), with a mean of 3.2±3.8 cases/patient. In total, 390 DRP were identified, of which 49.0% were related to "treatment effectiveness", 46.7% to "adverse reactions" and 1.0% to "treatment costs". The medicines most involved in DRP were Vancomycin (10.2%; n=46), Meropenem (8.0%; n=36) and Furosemide (7.1%; n=32). Pharmacists performed 331 interventions, of which 92.1% were accepted by physicians and nurses. Conclusions: The study showed that DRP are very frequent in patients with cardiac diseases hospitalized in the NICU, predominating problems related to the effectiveness and safety of the drug treatment.

RESUMO Objetivo: Determinar a frequência e a natureza dos problemas relacionados a medicamentos (PRMs) em neonatos cardiopatas internados em uma unidade de terapia intensiva. Métodos: Trata-se de um estudo transversal prospectivo desenvolvido na Unidade de Terapia Intensiva Neonatal (UTIN) de uma maternidade de ensino do Brasil, de janeiro de 2014 a dezembro de 2016. Todos os neonatos diagnosticados com alguma doença cardíaca (cardiopatias congênitas, cardiomiopatias, arritmias etc.) e internados na UTIN por período superior a 24 horas, com pelo menos um medicamento prescrito, foram incluídos no estudo. Dados demográficos e clínicos foram coletados a partir dos registros do serviço de farmácia clínica da instituição. Os PRMs e suas respectivas intervenções foram revisadas e classificadas independentemente por dois farmacêuticos. A classificação dos PRMs foi realizada por meio do sistema Pharmaceutical Care Network Europe versão 6.2. Resultados: Cento e vinte e dois neonatos foram incluídos no estudo. A frequência de neonatos expostos a PRM foi de 76,4% (intervalo de confiança de 95% [IC95%] 65,9-82,0), com média de 3,2±3,8 casos por paciente. Ao todo, 390 PRM foram identificados, sendo que 49,0% estiveram relacionados à "efetividade do tratamento", 46,7% a "reações adversas" e 1,0% a "custos do tratamento". Os medicamentos mais envolvidos em PRM foram: vancomicina (10,2%; n=46), meropenem (8,0%; n=36) e furosemida (7,1%; n=32). Os farmacêuticos realizaram 331 intervenções, sendo 92,1% aceitas por médicos e enfermeiros. Conclusões: O estudo mostrou que PRMs são muito frequentes em pacientes cardiopatas internados em UTIN, predominando problemas relacionados à efetividade e segurança do tratamento medicamentoso.

Vancomycin-induced severe thrombocytopenia in a young infant

Abstract Vancomycin is a first-line drug for treating methicillin-resistant Staphylococcus aureus. Thrombocytopenia is a rare adverse reaction to vancomycin treatment, and there are no reports of vancomycin-induced thrombocytopenia (VIT) in infants. We describe the case of a 3-month-old girl who was diagnosed with purulent meningitis. After 13 days of treatment with vancomycin, her platelet count reduced to 8 × 109/L. Vancomycin was discontinued, and intravenous methylprednisolone was administered. The platelet count returned to normal after 4 days. Patients, especially young children, receiving vancomycin for a long clinical course should undergo careful monitoring of laboratory indicators and blood tests.

Interaction study between vancomycin and liposomes containing natural compounds against methicillin-resistant Staphylococcus aureus clinical isolates

ABSTRACT The treatment of infections caused by resistant microorganisms is limited, and vancomycin (VAN) treatment failures for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are not uncommon, even when MRSA clinical isolates are susceptible to VAN. Thus, this study proposed the association of VAN with usnic acid and ß-lapachone encapsulated into liposomes as a novel therapeutic option for infections caused by MRSA. Liposomes containing ß-lap (ß-lap-lipo) or usnic acid (UA-lipo) were prepared by the thin lipid film hydration method followed by sonication. Antimicrobial activity against MRSA clinical isolates was investigated by the microdilution method according to the Clinical and Laboratory Standards Institute (CLSI). The interaction studies were carried out using the checkerboard method and epsilometer test (Etest). The interaction between VAN and ß-lap or ß-lap-lipo was synergistic (FICI = 0.453 and FICI = 0.358, respectively). An additive interaction between VAN and UA (FICI = 0.515) was found. UA-lipo resulted in synergism with VAN (FICI = 0.276). The Etest reproduced the results obtained by the checkerboard method for approximately 82% of the analysis. Thus, the present study demonstrated that VAN in combination with UA-lipo, ß-lap or ß-lap-lipo synergistically enhanced antibacterial activity against MRSA

Vancomycin-associated linear IgA disease mimicking toxic epidermal necrolysis

Abstract Linear IgA dermatosis is a rare subepidermal autoimmune blistering disease characterized by linear deposition of IgA along the basement membrane zone. In the last three decades, many different drugs have been associated with the drug-induced form of the disease, especially vancomycin. We report a case of vancomycin-induced linear IgA disease mimicking toxic epidermal necrolysis. The aim of this work is to emphasize the need to include this differential diagnosis in cases of epidermal detachment and to review the literature on the subject and this specific clinical presentation.

Case report of vancomycin-induced pancytopenia

Abstract: Vancomycin is the first-line agent for the treatment of bacteremia, endocarditis, pneumonia, cellulitis, and osteomyelitis. Pancytopenia is an uncommon adverse effect of vancomycin therapy, with only a few cases of vancomycin-related neutropenia and pancytopenia described in the literature. We describe a case of a 56-year-old man who was diagnosed with chronic paraspinal abscess and started on intravenous vancomycin. He was re-admitted two weeks later with new-onset pancytopenia. Discontinuation of vancomycin resulted in improved cell counts. Physicians should monitor cell counts in patients who are on long-term intravenous vancomycin.

Fatores de risco associados à lesão renal aguda em pacientes tratados com polimixina B em um hospital terciário / Risk factors for acute kidney injury in patients treated with polymyxin B at a Tertiary Care Medical Center

Resumo Introdução: O uso de polimixinas foi praticamente abandonado nos anos 1970 devido as altas taxas de nefropatia. Entretanto, foram reintroduzidas na prática médica devido a sua ação contra bactérias gram negativas resistentes a carbapenemicos. A literatura recente sugere uma taxa de nefropatia mais baixa do que a historicamente reportada. Objetivo: Determinar a incidência de nefropatia associada ao uso de polimixina utilizando os critérios de RIFLE. Métodos: Foi realizada coorte retrospectiva de todos pacientes adultos que receberam polimixina B no Hospital Nossa Senhora da Conceição de dezembro de 2010 até março de 2011. Resultados: 61 pacientes (43%) preencheram os critérios de rifle para injúria renal e 28 (13,7%) necessitaram de diálise. Preditores independentes para nefrotoxicidade foram hipotensão (OR, 2.79; CI 1.14-5.8; p = 0.006) e uso concomitante de vancomicina (OR, 2.86; CI, 1.27-6.4; p = 0.011). Conclusão: Nessa coorte retrospectiva, nefrotoxicidade (definida pelos criterios de RIFLE) ocorreu em 43% dos pacientes tratados com polimixina B. O uso concomitante de vancomicina e hipotensão foram fatores de risco independentes para desenvolvimento de nefropatia. Mais estudos são necessarios, particularmente com polimixina B, para esclarecer se as caracteristicas dessa droga e da colistina são sobreponíveis.

Abstract Introduction: Polimyxins were originally abandoned due to high rates of nephrotoxicity. However they have been recently reintroduced due to activity against carbapenem-resistant Gram-negative organisms. Recent literature suggests a lower rate of nephrotoxicity than historically reported. Objective: To determine the rate of polymixins-associated nephrotoxicity as defined by the RIFLE criteria. Methods: A retrospective cohort of all adult patients who received polymixin B at a terciary hospital from December 2010 to March 2011was performed. Results: 61 patients (43%) fulfilled the RIFLE criteria for renal injury and 28 patients (13.7%) needed dialysis. Independent predictors for nephrotoxicity were hypotension (OR, 2.79; CI 1.14-5.8; p = 0.006) and concomitant use of vancomycin (OR, 2.86; CI, 1.27-6.4; p = 0.011). Conclusions: In this retrospective cohort, nephrotoxicity (as defined by RIFLE criteria) occurred among 43% of treated patients. The concomitant use of vancomycin and hypotension were independent risk factors of nephropathy. Further studies are needed, particularly with polymyxin B, to clarify if the characteristics of this drug and colistin are overlapping.

Reposicionando la cloxacilina como antibioticoterapia empírica inicial de la sepsis tardía neonatal / Reinstating cloxacilin for empiric antibiotic in late-onset sepsis

Vancomycin has been used for more than 50 years in neonatal intensive care units (NICUs) as the therapy of choice for late-onset sepsis, mainly because Coagulase negative Staphylococci (CoNS) are common and mostly resistant to oxacyllin despitelow virulence and unusual association with fulminant sepsis. CUs due to several factors including its high pharmacokinetic variability, difficulty in reaching therapeutic plasmatic drug concentrations and progressively increasing minimum inhibitory concentrations (MIC). The increase of CoNS with higher MICs as well as the rise of infections caused by resistant gram-negative bacilli and candida should move to reconsider Vancomycin as first line treatment. Infections in neonates have a different behavior than in other populations and we consoder of utmost importance to consider the use of oxacyllin as first line antimicrobial therapy for late-onset sepsis.

Vancomicina se utiliza hace más de 50 años en unidades de cuidados intensivos neonatales (UCIN) como terapia de elección en sospecha de sepsis neonatal tardía; su principal indicación se fundamenta en que Staphylococcus coagulasa negativa (SCN) es el principal microorganismo que ocasiona sepsis tardía y éste es habitualmente resistente a cloxacilina; sin embargo, su virulencia es baja y la sepsis fulminante es inusual. Lamentablemente la prescripción de vancomicina se ha convertido en un grave problema en las UCIN, debido a diversas razones incluyendo: alta variabilidad farmacocinética del fármaco, dificultad en alcanzar concentraciones plasmáticas apropiadas y aumento de la concentración inhibitoria mínima (CIM), implicando además una mayor probabilidad de seleccionar cepas resistentes y aumento de otro tipo de infecciones ocasionadas por bacilos gramnegativos resistentes y candidiasis invasora. Considerando lo anteriormente señalado y a lo publicado en la literatura médica con respecto a las infecciones en neonatología, debido a su comportamiento clínico diferente a hospederos en otras etapas de la vida, resulta de suma importancia replantear el uso de vancomicina basado en fundamentos teóricos que avalen la seguridad de no utilizar este antimicrobiano como primera línea en sepsis neonatal tardía.

Meta-análise Cochrane: teicoplanina versus vancomicina para infecções suspeitas ou confirmadas / Cochrane meta-analysis: teicoplanin versus vancomycin for proven or suspected infection

Objective: To compare efficacy and safety of vancomycin versus teicoplanin in patients with proven or suspected infection. Methods: Data Sources: Cochrane Renal Group's Specialized Register, CENTRAL, MEDLINE, EMBASE, nephrology textbooks and review articles. Inclusion criteria: Randomized controlled trials in any language comparing teicoplanin to vancomycin for patients with proven or suspected infection. Data extraction: Two authors independently evaluated methodological quality and extracted data. Study investigators were contacted for unpublished information. A random effect model was used to estimate the pooled risk ratio (RR) with 95% confidence interval (CI). Results: A total of 24 studies (2,610 patients) were included. The drugs had similar rates of clinical cure (RR: 1.03; 95%CI: 0.98-1.08), microbiological cure (RR: 0.98; 95%CI: 0.93-1.03) and mortality (RR: 1.02; 95%CI: 0.79-1.30). Teicoplanin had lower rates of skin rash (RR: 0.57; 95%CI: 0.35-0.92), red man syndrome (RR: 0.21; 95%CI: 0.08-0.59) and total adverse events (RR: 0.73; 95%CI: 0.53-1.00). Teicoplanin reduced the risk of nephrotoxicity (RR: 0.66; 95%CI: 0.48-0.90). This effect was consistent for patients receiving aminoglycosides (RR: 0.51; 95%CI: 0.30-0.88) or having vancomycin doses corrected by serum levels (RR: 0.22; 95%CI: 0.10-0.52). There were no cases of acute kidney injury needing dialysis. Limitations: Studies lacked a standardized definition for nephrotoxicity. Conclusions: Teicoplanin and vancomycin are equally effective; however the incidence of nephrotoxicity and other adverse events was lower with teicoplanin. It may be reasonable to consider teicoplanin for patients at higher risk for acute kidney injury.

Objetivo: Comparar eficácia e toxicidade da teicoplanina e da vancomicina em pacientes com infecção suspeita ou confirmada. Métodos: Fontes de dados: Cochrane Renal Group's Specialized Register, CENTRAL, MEDLINE, EMBASE, livros de referência e artigos de revisão. Critérios de inclusão: Ensaios clínicos controlados randomizados em qualquer idioma, comparando teicoplanina e vancomicina em pacientes com infecção suspeita ou confirmada. Extração de dados: Dois autores avaliaram a qualidade metodológica dos estudos e extraíram os dados de forma independente. Tentou-se obter dados não publicados diretamente com os autores de cada trabalho. Usou-se um modelo de efeito aleatório para estimar a razão de risco (RR) combinada, com um intervalo de confiança (IC) de 95%. Resultados: Foram incluídos 24 estudos (2.610 pacientes). As drogas tiveram taxas semelhantes de cura clínica (RR: 1,03; IC95%: 0,98-1,08), cura microbiológica (RR: 0,98; IC95%: 0,93-1,03) e mortalidade (RR: 1,02; IC95%: 0,79-1,30). A teicoplanina apresentou menores incidências de rash cutâneo (RR: 0,57; IC95%: 0,35-0,92), síndrome do homem vermelho (RR: 0,21; IC95%: 0,08-0,59) e eventos adversos em geral (RR: 0,73; IC95%: 0,53-1,00). A teicoplanina reduziu o risco de nefrotoxicidade (RR: 0,66; IC95%: 0,48-0,90). Esse efeito foi consistente em todos os subgrupos, inclusive aqueles com pacientes recebendo aminoglicosídeos concomitantes (RR: 0,51; IC95%: 0,30-0,88) oucom dosagens de vancomicina corrigidas pelo nível sérico (RR: 0,22; IC95%: 0,10-0,52). Não foi encontrado nenhum caso de injúria renal que necessitasse de diálise. Limitações: Os estudos não seguiram uma definição padrão de nefrotoxicidade. Conclusões: Teicoplanina e vancomicina têm eficácia semelhante; no entanto, o risco de nefrotoxicidade e outros eventos adversos foi menor com teicoplanina. É razoável considerar o uso de teicoplanina para pacientes em risco de desenvolver injúria renal aguda.

Resumenes de articulos de la literatura pediatrica: vancomicina en combinación con otros antimicrobianos en el tratamiento de infecciones graves por staphylococcus aureus meticilino-resistente / Abstracts of articles in the pediatric literature: vancomycin in combination with other antimicrobials in the treatment of serious infections due to methicillin-resistant staphylococcus aureus

La vancomicina frecuentemente es combinada con otros antimicrobianos debido a su deficiencia en el tratamiento de infecciones graves por Staphylococus aureus meticilino resistente (MRSA).

A patient with penicillin-resistant viridans group streptococcal endocarditis and unusual reactions to vancomycin.

There is a paucity of data regarding the treatment of endocarditis caused by penicillin-resistant viridans group streptococci (PR-VGS). We report a 16-year-old girl who had native-valve endocarditis due to PR-VGS which was identified as Streptococcus mitis. She also had unusual reactions to vancomycin. Eighteen hours after initiation of 50 mg/kg/day vancomycin, she developed a maculopapular rash, then at 48 hours she developed an intermittent high fever and a progressive decrease in peripheral leukocytes and platelets. She developed hypotension on Day 8. Her serum C-reactive protein and procalcitonin levels were high. All reactions improved after vancomycin was discontinued and oral prednisolone was started. This unusual combination of reactions to vancomycin was likely caused by immune and nonimmune mechanisms. Her endocarditis was successfully treated with cefotaxime 200 mg/kg/ day for 4 weeks.

Reações cutâneas provavelmente atribuídas ao uso de fenitoína e vancomicina / Skin reactions probably attributed to the use of phenytoin and vancomycin

Reações cutâneas são as reações adversas mais comuns atribuídas a medicamentos. A síndrome de Stevens-Johnson ou eritema multiforme é uma reação grave e aguda determinada por medicamentos, especialmente aspirina, fenitoína e vancomicina. Relata-se o caso de uma mulher de 36 anos que desenvolveu a síndrome de Stevens-Johnson e três casos de pacientes que desenvolveram rash cutâneo após o recebimento de fenitoína e vancomicina.

A Case of Hypersensitivity Syndrome to Both Vancomycin and Teicoplanin

Drug hypersensitivity syndrome to both vancomycin and teicoplanin has not been previously reported. We describe here a 50-yr-old male patient with vertebral osteomyelitis and epidural abscess who developed hypersensitivity syndrome to both vancomycin and teicoplanin. Skin rash, fever, eosinophilia, interstitial pneumonitis, and interstitial nephritis developed following the administration of each drug, and resolved after withdrawing the drugs and treating with high dose corticosteroids. The vertebral osteomyelitis was successfully treated with 6-week course of linezolid without further complications. Skin patch tests for vancomycin and teicoplanin was done 2 months after the recovery; a weak positive result for vancomycin (10% aq.,+at D2 and +at D4 with erythema and vesicles; ICDRG scale), and a doubtful result for teicoplanin (4% aq.-at D2 and+/-at D4 with macular erythema; ICDRG scale). We present this case to alert clinicians to the hypersensitivity syndrome that can result from vancomycin and teicoplanin, with possible cross-reactivity, which could potentially be life-threatening.

Emissões otoacústicas produto de distorção em recém-nascidos medicados com ototóxicos / Distortion product otoacustic emission in newborn exposed to ototoxic

O objetivo deste estudo prospectivo longitudinal foi pesquisar a amplitude das emissões otoacústicas produto de distorção, em recém-nascidos medicados com ototóxicos. Formou-se um grupo controle com recém-nascidos saudáveis e de termo; um grupo de estudo com recém nascidos de termo exposto a amicacina e/ou vancomicina e um grupo de estudo com recém-nascidos pré-termo exposto aos mesmos ototóxicos. Os estudos provam que entre 15 e 40 dias, as amplitudes das emissões otoacústicas dos recém-nascidos do grupo de estudo pré-termo foram menores que os outros grupos. Nesse período as amplitudes aumentaram nos três grupos. Conclui-se que a há aumento da amplitude das emissões otoacústicas produto de distorção após o nascimento, sugerindo amadurecimento das estruturas cocleares no período pós-natal. A exposição a amicacina e vancomicina não alterou as amplitudes das emissões nos recém-nascidos / The aim of this prospective longitudinal study is to research the amplitude of distortion product otoacoustic emissions in newborns medicated with ototoxic drugs. Three groups were formed: a control group with term and healthy newborns; a study group composed by term newborns treated to amicacin and/or vancomycin; and a study group composed by preterm newborns exposed to the same ototoxic. The studies show that between 15 to 40 days the otoacoustic emissions amplitudes of the preterm study group were smaller than the other groups. In this period the amplitudes increased in the three groups. It was concluded that there is an increase of the distortion product otoacoustic emissions amplitude after birth, suggesting a maturation of the cochlear structures in the post-natal period. The exposure to amicacin and vancomycin did not alter the amplitude of the newborns’ emissions...

Maculopatia isquêmica após injeção intravítrea de amicacina: relato de caso / Macular infarction after intravitreal injection of amikacin: case report

Apresenta-se um caso de maculopatia isquêmica, secundária a injeção intravítrea de amicacina em paciente de 38 anos que apresentou endoftalmite após facoemulsificação com implante de lente intra-ocular. O tratamento foi realizado por meio de injeção intravítrea de amicacina, vancomicina e dexametasona. Após a melhora do quadro clínico, observou-se obstrução arteriolar na região macular. Embora a amicacina seja efetiva, por via intravítrea, para o tratamento de endoftalmite, pode causar infarto macular e baixa de acuidade visual significativa.

Agranulocytosis Induced by Vancomycin in an ESRD Patient on CAPD

Agranulocytosis is a rare adverse effect associated with prolonged vancomycin therapy, and is potentially serious, especially in end stage renal disease (ESRD) patients. We describe a continuous ambulatory peritoneal dialysis (CAPD) patient that developed vancomycin-induced agranulocytosis during treatment for methicillin-resistant Staphylococcus aureus (MRSA) -associated external cuff infection and pneumonia. The agranulocytosis was rapidly resolved by granulocyte colony-stimulating factor (G-CSF) therapy and by the discontinuation of vancomycin.

Role of fish oil and vitamin c in protection against nephrotoxicity induced by vancomycin in albino rat

This study aimed to investigate the role of fish oil and vitamin C alone and in combination in renal protection from vancomycin induced nephrotoxicity. Forty adult male albino rats were used in this study and were divided into eight groups of five animals each. The duration of the experiment was ten days, then all the animals were sacrificed and blood samples were collected to investigate the renal functions [blood urea nitrogen and serum creatinine]. Lipid peroxidase activity in both plasma and renal tissue was also estimated. Both kidneys were removed and prepared for histological examination. The results showed that vitamin C induced significant improvement of vancomycin nephrotoxicity. On the other hand, fish oil induced less significant improvement. The maximum protection was observed following combination of both vitamin C and fish oil with vancomycin. This protective effect was obtained both biochemically and histologically

Vancomycin-Resistant Enterococcus faecium: first case in Brazil

We report a fatal case of septicemia due to a vancomycin-resistant Enterococcus faecium in a 9 year-old girl with aplastic anemia. The isolate was also resistant to amplicillin, teicoplanin, gentamicin (high level), and streptomycin (high level). We believe that this is the first case of vancomycin-resistant Enterococcus (VRE) reported from a clinical specimen in Brazil.

Adverse aeffects of vancomycin in children: a review of 22 cases

Vancomycin has been frequently recommended for the treatment of multi-resistant infections. Twenty-two children undergoing vancomycin treatment were observed. Nine adverse effects were registered in 6 children: eosinophilia in 5 cases, skin rash in 2 cases, and an increase in plasma creatinine in 2 cases. All adverse effects remitted with withdrawal of the drug.