Efetividade da infusão estendida de Piperacilina-tazobactana - Meropenem no tratamento de pacientes sépticos adultos queimados através da modelagem farmacocinética farmacodinâmica, PK/P / Meropenem and piperacillin/tazobactam by extended infusion and PK/PD approach for drug effectiveness

Introdução: Meropenem (MER) e Piperacilina/Tazobactana (PTZ) são agentes antimicrobianos largamente prescritos para pacientes grandes queimados internados em Unidade de Terapia Intensiva (UTI) com infecções nosocomiais causadas por Gram-negativos sensíveis CIM 2 mg/L, Enterobacteriaceae, EB e Non-enterobacteriaceae, NEB. A síndrome da resposta inflamatória sistêmica (SRIS) que ocorre durante o choque séptico no grande queimado pode causar alteração na farmacocinética do paciente em terapia intensiva, de modo que a dose recomendada pode não atingir o alvo desejado contra Gram-negativos de sensibilidade intermediária CIM >2 mg/L. Objetivo: Investigar a efetividade dos beta-lactâmicos piperacilina e meropenem na infusão estendida comparada à infusão intermitente recomendada, para os pacientes sépticos grandes queimados através da abordagem farmacocinética-farmacodinâmica (PK/PD). Ética, casuística e procedimentos: Autor e co-autores declararam não haver conflito de interesse. O protocolo foi aprovado, registro CAAE 07525118.3.0000.0068. No presente protocolo de estudo investigaram-se 36 pacientes sépticos grandes queimados, ambos os gêneros (12F/24M) em terapia intensiva do choque séptico com piperacilina-tazobactana 4,5g q6h ou meropenem 1g q8h. Os pacientes incluídos foram estratificados em dois grupos com base na administração através da infusão intermitente, 0,5 h (G1) ou da infusão estendida, 3 h (G2), ambos com 16 pacientes cada. Duas amostras sanguíneas (1,5mL/cada) foram coletadas no estado de equilíbrio (Steady State), 3ª e 5ª hora do início da infusão. Os níveis séricos de PTZ e MER foram mensurados através de cromatografia líquida, e a farmacocinética (PK) dos dois grupos de pacientes foi comparada aos dados reportados em voluntários sadios. A abordagem PK/PD foi aplicada para avaliação da cobertura do antimicrobiano a partir da estimativa do índice de predição de efetividade (% fΔT>CIM) e da probabilidade de alcançar o alvo terapêutico (PTA) com base no alvo PK/PD recomendado, 100%fΔT>CIM. Resultados e discussão: As características de admissão dos pacientes G1/G2 foram expressas através de mediana e interquartil: Clcr 115 (90-148) / 127 (90-170) ml/min; 30 (24-31) / 27 (24- 33,5) anos, 70 (61-75) / 71 (65-75) kg, 30 (20-42) / 33,9 (18-38,4)% área total de superfície queimada, SAPS3 53 (45-57) / 48 (37,8-59,5). Na admissão dos pacientes na UTI registrou-se G1/G2: trauma térmico (17/16), trauma elétrico (1/2), lesão inalatória (11/11), ventilação mecânica (16/9) e vasopressores foram necessários em 15/8 pacientes, G1/G2. Ocorreram diferentes alterações na farmacocinética dos dois beta-lactâmicos após a infusão estendida versus a infusão intermitente quando comparadas com dados relatados em voluntários sadios. Evidenciou-se prolongamento da meia vida decorrente do aumento do volume de distribuição. Estes resultados impactaram diferentemente a cobertura. O monitoramento de biomarcadores inflamatórios expressos em medianas (G1/G2) evidenciou aumento do PCR: 232/183mg/L e leucocitose (leucócitos 11/14 mil cel/mm3, neutrófilos 9/10 mil cel/mm3) na fase precoce do choque séptico. Relativamente à microbiologia dos isolados, a erradicação dos patógenos ocorreu para todos os pacientes após a infusão estendida contra Gram-negativos sensíveis (CIM: 2 mg/L), e de sensibilidade intermediária (CIM 4mg/L) como a K. pneumoniae e P. aeruginosa, enquanto a infusão intermitente garantiu erradicação de patógenos apenas até CIM 2 mg/L. Conclusão: Evidenciou-se a superioridade da infusão estendida frente à infusão intermitente na cobertura dos dois antimicrobianos, no alvo terapêutico considerado 100%fΔT>CIM. Registraram-se alterações na farmacocinética destes agentes nos pacientes frente aos dados reportados para voluntários sadios. Diferença significativa entre grupos (G1/G2) foi encontrada com relação meia vida biológica, e ao volume de distribuição tanto pata a piperacilina quanto para o meropenem

Background: Meropenem (MER) and Piperacillin/Tazobactam (PTZ), antimicrobial betalactam agents are widely prescribed to burn patients from the Intensive Care Unit (ICU) with nosocomial infections caused by Gram-negative strains. Change in the pharmacokinetics of critically ill patient occurs during the systemic inflammatory response syndrome (SIRS) at the course of septic shock. Then, the recommended dose administered by intermittent infusion, 0.5 hr cannot reach the target against gram-negative strains MIC > 2 mg/L. Subject: To investigate drug effectiveness of the beta-lactams piperacilin and meropenem in extended infusion compared to the recommended intermittent infusion in critically ill septic burn patients using pharmacokinetic-pharmacodynamic (PK/PD) approach. Ethics, Casuistry and Methods: All authors declared there is no conflict of interests. Ethical approval CAAE, register 07525118.3.0000.0068. It was investigated in the study protocol 36 septic burn patients of both genders (12M / 24F), undergoing antimicrobial therapy with PTZ 4.5 g q6h or MER 1g q8h. Based on the chosen antimicrobial therapy and drug infusion prescribed by the physician, patients were stratified in groups with intermittent 0.5h infusion (G1) or with the extended 3h infusion (G2), both groups with 16 patients each. Two blood samples were collected at the steady state (1.5mL / each), at the 3rd and 5th hrs of starting the infusion. Serum levels were measured by liquid chromatography. Pharmacokinetics (PK) of MER or PTZ was compared to data reported in healthy volunteers for both groups of patients. PK/PD approach was applied to estimate the drug effectiveness index (fΔT> MIC) and to assess the probability of target attained (PTA) based on the recommended PK/PD target, 100% fΔT> MIC. Results and discussion: Characteristics of patients admission G1/G2 were: Clcr 115(90- 148)/127(90-170) ml/min; 30(24-31)/27(24-34) yrs, 70(61-75)/71(65-75) kg, 30(20- 42)/33.9(18-38.4)% total burn surface area, SAPS3 53(45-57)/48(37.8-59.5), medians (interquartile): thermal trauma occurred (17/16), electric trauma (1/2), inhalation injury (11/11), mechanical ventilation (9/16) and vasopressors required in 15/8 patients. It was demonstrated that different PK changes occurred for both beta-lactam agents after the extended or intermittent infusion by comparison with data reported in healthy volunteers. PK changes were related to the prolongation of biological half-life and increases on volume of distribution with impact on pharmacodynamics. On the other hand, meropenem total body clearance reduced by 50% at the earlier period of septic shock could be explained by the reduction of MER-transporters expression in the tubular renal secretion, once only patients with renal function preserved were included in the study protocol. Inflammatory biomarkers increased at the earlier period of septic shock: C-rp 232/183mg/L; leukocytes 11/14*103cel/mm3, neutrophils 9/10*103cel/mm3, medians, G1/G2. Clinical and microbiological cure was obtained for all patients of G1 against MIC < 2mg/L after intermittent 0.5 h infusion; while PK/PD target was attained for G2 patients undergoing antimicrobial therapy with MER or PTZ by extended infusion against gram negative strains K. pneumoniae, P. aeruginosa up to MIC 4mg L. Conclusion: Superiority of the extended infusion over intermitent infusion was obtained for the two antimicrobials was evidenced, in the therapeutic target considered 100%fΔT>CIM. Changes in the pharmacokinetics of these agents were recorded in patients compared to data reported for healthy volunteers. A significant difference between groups (G1/G2) was found in relation to biological half-life and volume of distribution for both piperacillin and meropenem

Parte IV. Terapia antimicrobiana en pacientes con cáncer y receptores de trasplante de precursores hematopoyéticos / Antimicrobial therapy in cancer patients and hematopoietic stem cell transplantation receptors

Resumen Este documento incluye los recursos terapéuticos antiinfecciosos necesarios para pacientes inmunocomprometidos por terapia de cáncer o receptores de trasplante de precursores hematopoyéticos (TPH). Se aborda la terapia indicada para pacientes con las situaciones clínicas prevalentes en esta población y la terapia indicada para algunos microorganismos específicos. Según presentación clínica, se aborda el manejo de pacientes con: neutropenia febril sin foco, sepsis, infecciones del sistema nervioso central, neumonía, infecciones de piel y tejidos blandos, enterocolitis neutropénica e infección del tracto urinario. Se describe el arsenal terapéutico necesario, las dosis recomendadas y las precauciones especiales para el uso de antibacterianos, antivirales, antifúngicos y antiparasitarios en esta población, incluida la medición de concentraciones plasmáticas de ciertos fármacos en situaciones específicas.

This manuscript includes the antiinfective therapeutic resources for immunocompromised patients under chemotherapy by cancer or hematopoietic stem cells transplant (HSCT) receptors. The document presents the antimicrobial therapy indicated in the most prevalent clinical situations in this population and the primary and alternative therapy for some specific microorganisms. The clinical situations included in the analysis are: febrile neutropenia without focus, sepsis, infections of the central nervous system, pneumonia, skin and soft tissue infections, neutropenic enterocolitis and urinary tract infection. The therapeutic resources, recommended doses and special precautions for the use of antimicrobial recommended in bacterial, viral, fungal and parasitic infections in this population are described, including the measurement of plasma concentrations of certain drugs in specific situations.

Factors associated with compliance to guidelines on the use of antibiotics and correlated with clinical outcomes of pregnant women admitted in the Department of Obstetrics and Gynecology of a tertiary hospital from January 1, 2018 to December 31, 2018

BACKGROUND@#Antimicrobial therapy is an integral part of an acceptable clinical practice in Obstetrics and Gynecology. However, in order for these antimicrobials to deliver the desired clinical outcome, the practice of judicious antibiotic stewardship should be observed. The objective of the study was 1.) To determine the proportion of pregnant women admitted at the Department of Obstetrics and Gynecology who received antibiotics from January 1, 2018 to December 31, 2018, 2.) To determine the proportion of indications for antibiotic administration, 3.) To determine if indications for antimicrobial usage is in accordance with the clinical case, policy guidelines, culture results and antibiogram report, 4.) To determine the percentage of cases not given antimicrobials that should have been started on antimicrobial therapy, 5.) To compare the association of the clinical outcomes among patients given and not given antimicrobials, 6.) To compare the association of the immediate neonatal outcomes among pregnant patients given and not given antimicrobials.@*METHODS@#A retrospective cohort study was done covering a period of 1 year from January to December 2018. The study included all pregnant patients who were admitted and listed based from the master list of the Department of Obstetrics and Gynecology. Included are all the retrieval charts from the records sections whereas gynecologic and those cases with medical records not retrieved were excluded. A total of 3,495 obstetrics patients admitted from January to December 2018 were retrospectively studied. From this group, the complete medical records of 1,092 obstetrics patients were retrieved and included in this study. Detailed clinical information, antibiotics administered, diagnostic and other relevant investigations, and clinical outcomes were recorded from case sheets. After the data were collected from patients' medical records, datas were manually entered into an electronic spreadsheet file, and the data processing and analysis were then carried out using statistical software Stata 13.@*RESULTS@#There were 1,092 women included in the current study with more than half of them administered or received antibiotics as part of their regimen (n = 663, 60.71 %) compared to those not administered antibiotics (n = 429, 39.29%). The results showed that the prevalence of obstetric patients (undelivered, delivered, ectopic pregnancy and abortion) prescribed and given antibiotics was between 57.75 to 63.62 per cent. There was no association between the comparison groups in terms of age (x 2 : 3.62, p: 0.31 ), marital status (x2 : 1.29, p: 0.26), body mass index classification (x 2 : 6.88, p: 0.08), hemoglobin level (x 2 : 1.74, p: 0.19), and number of prenatal consults (x2 : 3.13, p: 0.21 . There was a significantly higher proportion of women who delivered abdominally that were administered antibiotics (x 2 : 32.45, p<0.01) as compared to women who delivered vaginally (spontaneous or assisted), admitted due to ectopic pregnancy, abortion, and medical management. Cephalosporins are the most widely used antibiotics. Cefazolin (60.48%) followed by Cefuroxime (39.97%) were commonly used for pre-operative prophylaxis and urinary tract infection. Other commonly used antibiotics are Clindamycin (3.62%), Ampicillin (3.47%), Amikacin (2.56%), Ceftriaxone (2.11 %) and Doxycycline (1 .81 %). In 803 of cases (74.15%), reason for administration was not recorded in the chart and stated on working impression and final diagnosis. Majority of the antibiotics were empirically given (99.10%). The irrational use of antibiotics among those administered was observed in 564 cases (52.47%) (95% Cl: 49.46-55.47%). Rational use was only observed in 99 cases (19.08%). Among those not given antibiotics, 420 cases (80.92%) with adherence to antibiotic guidelines and 9 cases (52.47%) inappropriately not given antibiotics. It can also be noticed that there was an association between administration (and nonadministration) of antibiotics - and having an appropriate indication for such action (x2: 718.97, p<0.01 ). Maternal and neonatal outcomes showed that there was no noted association between the administration of antibiotics, and selected outcomes. Additional morbidity appeared to be slightly increased among those who were not given antibiotics than otherwise (z: -1.90, p: 0.60).@*CONCLUSION@#The study demonstrated that most of the antibiotic administration from January 1 to December 31, 2018

Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis / 中华危重病急救医学

Preclinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of preclinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling was held in Vienna in May, 2017. The goal of the conference was to identify limitations of preclinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Pre-clinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models. A total of 31 experts from 13 countries participated and were divided into six thematic Working Groups: Study Design, Humane modeling, Infection types, Organ failure/dysfunction, Fluid resuscitation, and Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2003-2012). Overall, the participants reached consensus on 29 points; 20 at "recommendation" and nine at "consideration" strength. This Executive Summary provides a synopsis of the MQTiPSS consensus. We believe that these recommendations and considerations will serve to bring a level of standardization to preclinical models of sepsis and ultimately improve translation of preclinical findings. These guideline points are proposed as "best practices" for animal models of sepsis that should be implemented. To encourage its wide dissemination, this article is freely accessible on the Intensive Care Medicine Experimental and Infection journal websites. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection, and Intensive Care Medicine Experimental.

Research progress on the pathogenesis and treatment of Enterococcus faecalis in pulp periapical disease / 口腔疾病防治

@#Enterococcus faecalis is an important pathogen in pulp periapical disease that has been widely studied in recent years. A large number of studies have shown that the high detection rate of Enterococcus faecalis in root canals with persistent or secondary infection after root canal therapy is closely related to the failure of root canal therapy. The presence of Enterococcus faecalis in periapical pulp disease is related to its pathogenicity and virulence factors. Enterococcus faecalis can directly invade host tissues or induce immune inflammation in host tissues, resulting in periapical pulp tissue damage and lesions. Enterococcus faecalis has a strong tolerance to conventional root canal antibiotics and disinfection methods and is difficult to completely remove from the complex root canal system. How to fight Enterococcus faecalis infection has become an important direction in the treatment of pulp periapical disease. This article reviews the pathogenic mechanism of Enterococcus faecalis infection in pulp periapical disease and the progress in its treatment.

Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for fluid resuscitation and antimicrobial therapy endpoints / 中华危重病急救医学

As outlined in the International Guidelines for Management of Sepsis and Septic Shock: 2016, initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part Ⅲ report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen(s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.

Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for fluid resuscitation and antimicrobial therapy endpoints / 中华危重病急救医学

As outlined in the International Guidelines for Management of Sepsis and Septic Shock: 2016, initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part Ⅲ report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen(s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.

Acute osteomyelitis

Acute osteomyelitis requires careful clinical evaluation, a high index of suspicion as it is an uncommon but devastating disease that affects largely previously healthy children. Management of osteomyelitis is a formidable challenge as success of antibiotics in soft tissues has not been replicated in bony tissue due to peculiar anatomy and physiology of the bone. Illness, malnutrition and decreased immunity predispose children to develop acute osteomyelitis. Absence of phagocytic cells in the metaphysis may explain predilection in children. Recently the trend in treatment strategy includes a rapid transition from intravenous to oral antimicrobial therapy and a shortened overall course of therapy. Many new therapeutic options are on the horizon that will likely impact the management of this and other childhood bacterial infections. This review will focus on recent advances in the management of acute hematogenous osteomyelitis in children.

Adverse drug reaction monitoring during antimicrobial therapy for septicemia patients at a university hospital in New Delhi

BACKGROUND/AIMS: Adverse drug reaction (ADR) is an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product. The present study was conducted in order to monitor the frequency and severity of ADR during antimicrobial therapy of septicemia. METHODS: A prospective, observational, and noncomparative study was conducted over a period of 6 months on patients of septicemia admitted at a university hospital. Naranjo algorithm scale was used for causality assessment. Severity assessment was done by Hartwig severity scale. RESULTS: ADRs in selected hospitalized patients of septicemia was found to be in 26.5% of the study population. During the study period, 12 ADRs were confirmed occurring in 9, out of 34 admitted patients. Pediatric patients experienced maximum ADRs, 44.4%. Females experienced a significantly higher incidence of ADRs, 66.7%. According to Naranjo’s probability scale, 8.3% of ADRs were found to be definite, 58.3% as probable, and 33.3% as possible. A higher proportion of these ADRs, 66.7% were preventable in nature. Severity assessment showed that more than half of ADRs were moderate. Teicoplanin was found to be the commonest antimicrobial agent associated with ADRs, followed by gemifloxacin and ofloxacin. CONCLUSIONS: The incidence and severity of ADRs observed in the present study was substantially high indicating the need of extra vigilant during the antimicrobial therapy of septicemia.

The effects of antimicrobial therapy on dendritic cells in the infected microenvironment of rabbit buccal VX-2 squamous cell carcinoma / 实用口腔医学杂志

Objective:To study the effects of antimicrobial therapy on the maturation and function of dendritic cells(DCs) in the infected microenvironment of rabbit buccal VX-2 squamous cell carcinoma.Methods:The inflammatory models were obtained by mechanical trauma and high sugar diet on the basis of rabbit buccal VX-2 squamous cell carcinoma models which were established by particle implantation of the tumor tissue.The model rabbits were divided into 3 groups (n =6).In group A the rabbits with buccal VX-2 squamous cell carcinoma and local inflammation were given antibiotics by gavage and intramuscular injection for 3 consecutive days;the rabbits in group B with buccal VX-2 squamous cell carcinoma and local inflammation were given normal saline by gavage and intramuscular injection;the rabbits in group C with tumor and without inflammation were given normal saline by gavage and intramuscular injection.The tumor specimens were collected 3 days after treatment,and made into tissue homogenate,supernatant was collected after centrifugation.Normal rabbit peripheral blood mononuclear cells were separated and co-cultured with the supernatant obtained from the 3 groups respectively.Expressions of DCs surface markers HLA-DR,CD83 and CD86 were detected by flow cytometry.the function of DCs was tested by mixed lymphocyte reaction.Results:The positive rate of HLA-DR,CD83,CD86 and stimulate index were group C ＞ group A ＞ group B (P ＜ 0.05).Conclusion:Antimicrobial therapy can promote the maturation and function of DCs in the infected microenvironment of rabbit buccal VX-2 squamous cell carcinoma.

Risk Factors for Mortality of Bloodstream Infections in Patients with Hematologic Diseases / 中山大学学报(医学科学版)

[Objective] To explore the risk factors for mortality of bloodstream infections in the patients with hematologic diseases,so as to provide evidence for reasonable and effective application of treatments.[Methods] The clinical data of 242 cases of bloodstream infections who were hospitalized from Jan 2012 to Jun 2016 were analyzed retrospectively,then the analysis was performed for risk factors.The statistical analysis was processed by SPSS 19.0.[Results] A total of 266 strains of pathogens were isolated,including 99 strains of gram-positive bacteria,accounting for 37.2％,and 164 strains of gram-negative bacteria,accounting for 61.7％.Multivariate analysis showed that the significant independent risk factors for mortality were active states of hematologic diseases (P =0.007,OR =5.622,95％ CI 1.586 ～ 19.924),presentation with septic shock(P =0.007,OR =4.978,95％ CI 1.560 ～15.884),cardiac insufficiency (P =0.001,OR =11.878,95％ CI 2.760 ～ 51.120),level of albumin less than 35 g/L (P =0.036,OR =3.468,95％ CI 1.087 ～ 11.066),polymicrobial infection (P =0.010,OR =6.024,95％ CI 1.540 ～ 23.563),and Staphylococcus haemolyticus (P =0.001,OR =19.308,95％ CI 3.392 ～ 109.888)/Enterococcus (P =0.002,OR =15.266,95％ CI 2.817 ～82.728) infection.The survival curves show that the inappropriate initial antimicrobial therapy group or presentation with any one of the independent risk factors had a lower probability of survival than the control group.[Conclusions] Bloodstream infections in patients may cause high mortality rate,so it is necessary that we use antibiotic reasonably and spare no effort to reduce the mortality rate by appropriate application of antimicrobial therapy and effective intervention of the risk factors.

Actualidades en infecciones vertebrales / Actualités sur les infections vertébrales / News on Vertebral Infections

Introducción: las infecciones vertebrales constituyen una afección de baja incidencia, pero con incremento importante en años recientes, el cual está en relación con una población más susceptible por diversas razones. A pesar de nuevos métodos para el diagnóstico, la demora constituye un importante problema. Propósito: revisar y discutir algunos temas actuales acerca de las infecciones vertebrales, la epidemiologia, etiología, fisiopatología, diagnóstico y tipos de tratamientos. Método: se seleccionó la literatura apropiada usando las bases de datos Pubmed, Hinari y Clinical Key. Resultados: la literatura muestra la importancia del correcto y rápido diagnóstico; determinar el agente causal es de primordial importancia para aplicar una adecuada terapia antimicrobiana. El tratamiento conservador produce, generalmente, buenos resultados y el quirúrgico está indicado en déficit o sepsis neurológicos, inestabilidad espinal y/o deformidad y fallo del tratamiento conservador. Se muestra algoritmo para diagnóstico y tratamiento. Conclusiones: aplicar una metodología correcta para el diagnóstico y tratamiento de las infecciones vertebrales, logra resultados satisfactorios(AU)

Introduction: vertebral infections are a disease of low incidence, but with significant increase in recent years. This increase is related to a more susceptible population due to various reasons. Despite the new methods for diagnosis, its delay is a major problem. Objective: review and discuss some current issues about the spine infections, epidemiology, etiology, pathophysiology, diagnosis and types of treatment. Method: select the appropriate literature using PubMed database, Hinari and Clinical Key. Results: the literature shows the importance of correct and rapid diagnosis, which determine the causal agent, is primordial to implement appropriate antimicrobial therapy. Conservative treatment generally produces good results and surgery is indicated in neurological deficit or sepsis, spinal instability and / or deformity and failure of conservative treatment. Diagnostic and treatment algorithm is shown. Conclusions: applying correct methodology for the diagnosis and treatment of spinal infection, satisfactory results are achieved(AU)

Introduction: les infections vertébrales sont des affections à faible incidence, mais d'un récent accroissement important. Cette augmentation est associée à une population plus sensible pour des raisons diverses. Malgré les nouvelles méthodes diagnostiques, le retard constitue un problème important. Objectif: le but de cette étude est d'examiner et discuter des questions actuelles sur les infections vertébrales, leur épidémiologie, leur étiologie, leur physiopathologie, leur diagnostic, et les types de traitement. Méthode: on a sélectionné une littérature appropriée au moyen des bases de données de PubMed, Hinari et Clinical Key. Résultats: la littérature montre l'importance d'un diagnostic correct et précoce; la définition de l'agent causal est d'une importance essentielle pour appliquer une adéquate thérapie antimicrobienne. En général, le traitement conservateur a de bons résultats, mais le traitement chirurgical est indiqué en cas de déficit ou sepsis neurologiques, d'instabilité et/ou déformation rachidienne, et d'échec du traitement conservateur. Un algorithme est présenté pour le diagnostic et le traitement. Conclusions: l'application d'une correcte méthodologie pour le diagnostic et le traitement des infections vertébrales assure des résultats satisfaisants(AU)

Efficacy and relapse rates of different treatment modalities for progressive macular hypomelanosis.

Background: Progressive macular hypomelanosis is an acquired disorder characterized by hypopigmented macules mostly on the trunk and upper extremities. Although many treatment modalities have been proposed for this condition with variable success rates, there are few reports comparing their efficacy and relapse rates. Aim: To compare the efficacy and relapse rates of different treatment modalities for progressive macular hypomelanosis. Methods: Case records of patients diagnosed with progressive macular hypomelanosis and treated in National Skin Centre for a six year period between 2008 and 2014 were reviewed. Patient demographics, distribution of hypopigmented macules, treatment efficacy and relapse rates were noted. Results: A total of 108 patients were seen for progressive macular hypomelanosis over the study period; of these, 40 opted for no treatment but were followed up. Thirty‑six were treated with topical antimicrobials and 32 with phototherapy. Of those untreated, 23% recovered spontaneously while 38% in the antimicrobial group and 90% in the phototherapy had remission of their hypopigmentation. After 2 years of follow‑up, relapse occurred only in the phototherapy group. Limitations: The main limitation is the retrospective design whereby diagnosis is dependent on the attending dermatologist. Conclusions: Narrow‑band ultraviolet B therapy appears to be the most effective treatment for progressive macular hypomelanosis but also has the highest potential for relapse. Response rates for antimicrobial therapy are lower and slower, but patients who responded did not relapse. A combination of topical/systemic antimicrobials with narrow‑band ultraviolet B therapy might be the best option to hasten recovery and minimize relapse.

Pharmacotherapy of Opportunistic Infections in HIV Patients: A Review.

With the introduction of antiretroviral therapy, there is a dramatic decrease in the morbidity and mortality related to human immunodeficiency virus (HIV) infections. Due to varying degree of immunosuppression, patients are prone to various number of infections in their lifetime. Respiratory system, central nervous system, gastrointestinal tract and the skin are the most susceptible for opportunistic infections. Timely management of these microbial infections followed by chemoprophylaxis is essential as per the guidelines for the management of opportunistic infections in HIV. The development of drug toxicities and drug resistance in managing patients with HIV has always remained a clinical challenge. Consideration is given to the numerous pharmacokinetic interactions between drugs used to treat and prevent opportunistic infections and antiretroviral drugs, along with complications like immune reconstitution inflammatory syndrome. Clinicians must be aware about optimal strategies present for diagnosis, prevention and treatment of opportunistic infections in order to improve health and provide high quality of care for the patients.

Experiencia en el tratamiento de la infección bacteriana en receptores de trasplante renal / Experience in the treatment of bacterial infection in renal transplant recipients

Introducción: el trasplante renal constituye la terapéutica de elección en el tratamiento de la enfermedad renal crónica, pero las complicaciones infecciosas, específicamente bacterianas, mantienen elevadas tasas de morbilidad y mortalidad y constituyen un problema de difícil solución. En el Hospital Universitario Arnaldo Milián Castro contamos con 8 años de experiencia en el tratamiento de la infección bacteriana en receptores de trasplante renal. Objetivo: caracterizar el comportamiento de la infección bacteriana en receptores de trasplante renal. Métodos: se efectuó un estudio descriptivo, longitudinal y prospectivo que incluyó a 102 pacientes receptores de TR con diagnóstico de infecciones bacterianas, entre junio de 2001 y diciembre de 2009, y 192 infecciones bacterianas confirmadas por estudios microbiológicos. Resultados: se localizaron 9 procesos infecciosos en el parénquima pulmonar con clínica, radiografía y respuesta antimicrobiana sin positividad en los especímenes recolectados y procesados en el laboratorio. El grupo etario más afectado fue el de 31 a 40 años con 32 procesos infecciosos. No hubo diferencias en cuanto al sexo ni a la relación sexo-edad. Predominó la piel blanca (74,5 por ciento) (x² BA= 0,064 p= 0,936). Los que exhibieron una sola infección fueron los más representados (50 por ciento) y el urocultivo fue el espécimen con más positividad, 94 para un índice de 0,92. Los grupos de pacientes con uno y dos episodios infecciosos tuvieron 2 fallecidos cada uno al egreso (p= 0,278). La infección del tracto urinario y la herida quirúrgica predominaron en el posoperatorio inmediato, con 16 casos, respectivamente, aunque la primera se presentó más frecuentemente en los diferentes períodos evolutivos. El microorganismo más resistente fue el Acinetobacter spp. en el cultivo de orina en 3 pacientes (10,34 por ciento) y el antimicrobiano menos efectivo, la combinación de amoxicilina-sulbactán, en 8 (21,05 por ciento). Conclusiones: el conocimiento de las características de la infección bacteriana en receptores de trasplante renal y la selección oportuna y específica del antimicrobiano a la dosis recomendada han sido las herramientas principales en nuestra experiencia(AU)

Introduction: renal transplantation is the therapy of choice in the treatment of chronic kidney disease, but specifically bacterial infectious complications maintain high rates of morbidity and mortality and it is a problem difficult to solve. At Arnaldo Milian Castro University, eight year-experience has been gained in the treatment of bacterial infection in renal transplant recipients. Objective: characterize the bacterial infection behavior in renal transplant recipients. Methods: a descriptive, longitudinal and prospective study was conducted from June 2001 to December 2009, in 102 patients receiving renal transplantation and who were diagnosed with bacterial infections; and 192 bacterial infections confirmed by microbiological education. Results: nine infectious processes were located in the pulmonary parenchyma with clinic, X-ray images and antimicrobial answer with no positiveness in the specimens gathered and processed in the laboratory. The most affected age group was 31 to 40 years with 32 infectious processes. There were no differences in gender or sex-age relationship. White skin subjects prevailed (74.5 percent) (x² BA = 0.064 p = 0.936). Those who exhibited a single infection were overrepresented (50 percent) and urine culture was more positive specimen, 94 for an index of 0.92. Patient groups one and two infectious episodes had 2 deaths each at discharge (p = 0.278). The wound and urinary tract infections prevailed in the immediate postoperative period, with 16 cases, respectively, although the latter was more likely at different evolutive periods. Acinetobacter spp was the most resistant microorganism in urine culture in 3 patients (10.34 percent) and the less effective antimicrobial was amoxicillin-sulbactam, in 8 (21.05 percent). Conclusions: the timely and specific selection of the antimicrobial drug at the recommended dose for each patient has been the main tool in our experience(AU)

Mycoplasma infection in Malaysian children: laboratory investigation and antimicrobial therapy.

Background: Mycoplasma pneumonia (M. pneumoniae) is an important causative agent of childhood infection with variable clinical presentations. The objective of the study was to evaluate the laboratory investigation and antimicrobial therapy of M. pneumoniae infection in children admitted to paediatric ward. Materials & Methods: A total of 111 children, of which 59 (53.2%) boys and 52 (46.8%) girls, with median age of 2 years (inter quartile range 1-6 years) with suspected M. pneumoniae infection were tested for IgM by enzyme-linked immunosorbent assay (ELISA). The children were classified as seropositive and seronegative. Results: Of the 111 children, 45 (40.5%) had serological evidence of M. pneumoniae infection and the remaining 66 (59.5%) were seronegative. There was significant association (p < 0.001) between age and serology response. Seropositive children were more likely to be older (median age 5.0 [interquartile range 2- 7] years, p < 0.001). Children with M. pneumoniae infection were less likely to have cough (p = 0.023) in which 55 (65.5%) patients having cough were seronegative. There was no significant association between laboratory findings of full blood count and serology. Conclusion: In addition to clinical and laboratory features, other factors like age group and absence of cough might be helpful in predicting M. pneumoniae infection.

Susceptibility and resistance to antimicrobial Staphylococcus aureus under biofilm / Susceptibilidade e resistência a antimicrobianos de Staphylococcus aureus em condições de biofilme

Staphylococcus is an important agent of mastitis, especially when biofilm producers are related to a number of mechanisms of resistance to different types of infections. The objective of this research was to evaluate the susceptibility and resistance of Staphylococcus aureus strains isolates from cases of bovine mastitis and milking environment under conditions of biofilm, compared to three different concentrations in different antimicrobials. Thirty-two strains used were S. aureus that, due to the inhibition tests, minimal biofilm eradication concentration were tested using cephalexin, amoxicillin and rifampin at concentrations of 30 mg/mL, and 50 mg/mL 100 mg/mL for 12 hours, and efficiency of tests evaluated by counting the colony forming units and the microplate test. The results revealed that among the tested antibiotics cephalexin showed the best efficiency at the three concentrations tested, and rifampin and amoxicillin were more efficient at concentrations of 50 and 100 mg/mL. These data demonstrate the importance of targeted antibiotic therapy associated with the correct cleaning of milking equipment, thus, preventing the formation of biofilm, avoiding persistent microbial adhesion in equipment, and the spread of microorganisms by ascending channel teats among herd animals.

Os Staphylococcus, principais agentes causadores da mastite, quando em biofilmes, estão relacionados a uma série de mecanismos de resistência em diferentes tipos de infecções. O presente trabalho avaliou a susceptibilidade e resistência dos Staphylococcus aureus, isolados de casos de mastite bovina e do ambiente de ordenha, em condições de biofilme, frente a três antimicrobianos distintos em diferentes concentrações. Foram utilizadas trinta e duas estirpes de S. aureus testadas frente aos testes de inibição da concentração mínima de erradicação de biofilmes, utilizando cefalexina, amoxicilina e rifampicina, nas concentrações de 30 mg/mL, 50 mg/mL e 100 mg/mL, por doze horas de contato, e a eficiência dos testes avaliada pela contagem das unidades formadoras de colônias e pelo teste de microplacas. Os resultados revelaram que, entre os antimicrobianos testados, a cefalexina foi o que apresentou melhor eficiência nas três concentrações testadas, e a rifampicina e amoxacilina tiveram maior eficiência nas concentrações de 50 e 100 mg/ mL. Esses dados demonstram a importância sobre antibioticoterapia orientada associada com a correta higienização dos equipamentos de ordenha, evitando-se, assim, a formação de biofilmes, a adesão microbiana persistente em equipamentos, e a difusão dos microrganismos pelo canal ascendente dos tetos entre os animais do rebanho.

Antimicrobial Therapy for Infections Caused by Multidrug-Resistant Gram-Negative Bacteria / 대한내과학회지

The incidence of infections caused by multidrug-resistant (MDR) Gram-negative bacteria has increased over the past decade and extensively drug-resistant (XDR) infections are now on the rise, especially in non-fermenters such as Pseudomonas and Acinetobacter species. Unfortunately, our therapeutic options for these pathogens are extremely limited. Infections due to antimicrobial-resistant bacteria are associated with a greater likelihood of inappropriate antimicrobial therapy, which has adverse effects on the outcomes of patients with serious infections. Physicians who are treating immunocompromised patients should be aware of not only the current epidemiological status of antimicrobial resistance but also appropriate antimicrobial therapy for MDR pathogens. Although carbapenems are considered a mainstay for the treatment of extended-spectrum beta-lactamase (ESBL) or AmpC beta-lactamase-producing pathogens, antimicrobial stewardship for the appropriate use of carbapenems should be implemented to preserve these important antimicrobial agents. For carbapenem-resistant XDR infections, colistin and tigecycline could be considered a therapeutic option, based on the in vitro antibacterial spectrum, although the optimum treatment has not been established. This review provides a recent update of the antimicrobial therapeutic strategies for serious infections due to MDR or XDR Gram-negative bacteria, such as ESBL-producers and carbapenem-resistant pathogens.

Osteomyelitis: A Descriptive Study

BACKGROUND: To analyze the incidence and clinical-microbiological characteristics of osteomyelitis (OM) in a tertiary Spanish hospital. METHODS: All cases diagnosed with OM between January 2007 and December 2010 were retrospectively reviewed. The variables examined include epidemiological characteristics, risk factors, affected bone, radiographic changes, histology, microbiological culture results, antibiotic treatment, and the need for surgery. RESULTS: Sixty-three cases of OM were diagnosed. Twenty-six patients (41.3%) had acute OM whereas 37 patients (58.7%) were classified as chronic OM. OM may result from haematogenous or contiguous microbial seeding. In this group, 49 patients (77.8%) presented with OM secondary to a contiguous source of infection and 14 patients had hematogenous OM (22.2%). Staphylococcus aureus was the most commonly found microorganism. CONCLUSIONS: OM mainly affected patients with risk factors related to the presence of vascular diseases. Antibiotic treatment must be guided by susceptibility patterns of individual microorganisms, although it must be performed together with surgery in most of the cases.

The pharmacoeconomics evaluation of two remedy scheme in curing acute cerebral infarction / 中国生化药物杂志

Objective To estimate the pharmacoeconomics of two remedy scheme in curing acute cerebral infarction. Method In 212 cases with acute cerebral infarction patients, 206 cases were adopted, and randomly divided into two group. Group A was 102 cases and Group B was 104 cases. Group A was administered with 18 ml cattle encephalon glycoside which was added into 250 ml 5%glucose injection, ivgtt, qd. After 7 days it was administered compound Butylphthalide Soft Capsules, 0.2 g qid, combined Xiaoshuantongluo capsule, 2.1 g tid until 14 days later. Group B was administered with cattle encephalon glycoside and ignotin injection 18 ml which was added into 250 ml 5%glucose injection, ivgtt, qd until 14 days. The basic therapy of two groups were same. After therapy compared the safety and clinic curative effect from European Stroke Scale(ESS) and activities of daily living(ADL).Then outcome-effectiveness was assayed in pharmacoeconomics. Results The total effective rate were 92.2 and 95.2%,and ccurrence of adverse react were 4.7 and 7.5, respectively,in the two group.The clinic total effective rate counting C/E was respectively 129.1 and 178.5;ΔC/ΔE was 1697.7. Conclusion The clinic curative effect of two group was intimate, but the cost had signiifcant difference. The sequential antimicrobial therapy in curing acute cerebral infarction had excellent advantage in outcome-effectiveness.