Caracterización clínico epidemiológica de los pacientes con infecciones por estafilococo dorado / Clinical-epidemiological characterization of patients with Staphylococcus aureus infections

RESUMEN Introducción: El estafilococo dorado es una causa importante de morbilidad y mortalidad en el mundo. En Cuba, es un germen a tener en cuenta como causa de infección intrahospitalaria. Objetivo: Caracterizar, clínica y epidemiológicamente, una muestra de pacientes con infecciones causadas por estafilococo dorado. Métodos: Se realizó un estudio observacional, descriptivo y transversal en el Hospital Militar "Dr. Mario Muñoz Monroy" de Matanzas, durante el período de enero a diciembre del año 2014. La población estuvo constituida por la totalidad de los pacientes hospitalizados con el diagnóstico de infección por estafilococo dorado (120 casos), identificados por el departamento de Microbiología; luego se revisaron las historias clínicas de las cuales se obtuvo la información. Resultados: Existió un predominio del sexo masculino (64,2 por ciento), los mayores de 60 años fueron los más afectados (36,7 por ciento). La diabetes mellitus fue la enfermedad asociada más frecuente (40,8 por ciento) y la mayoría de las infecciones fueron de origen comunitario (67,5 por ciento). Los aislamientos predominaron en las muestras tomadas de las lesiones en piel y los hemocultivos con un 50,8 por ciento y 19,2 por ciento, respectivamente. Se evidenció baja sensibilidad a la vancomicina (49,2 por ciento) y al cotrimoxazol (38,3 por ciento). Conclusiones: Las infecciones por estafilococo dorado fueron más frecuentes en pacientes masculinos geriátricos de su origen extrahospitalario. El germen presentó alta resistencia a los antibióticos y de estos, los aminoglucósidos mostraron la mayor sensibilidad antimicrobiana(AU)

Introduction: Staphylococcus aureus is an important cause of morbidity and mortality in the world. In Cuba, it is a germ to be taken into account as a cause of nosocomial infection. Objective: To characterize, clinically and epidemiologically, a sample of patients with infections caused by Staphylococcus aureus. Methods: An observational, descriptive and cross-sectional study was conducted at the Military Hospital "Dr. Mario Muñoz Monroy "of Matanzas, during the period from January to December of the year 2014. The population was constituted by all the patients hospitalized with the diagnosis of infection by Staphylococcus aureus (120 cases), identified by the department of Microbiology; then the medical records from which the information was obtained were reviewed. Results: There was a predominance of males (64.2 percent) those over 60 were the most affected (36.7 percent). Diabetes mellitus was the most frequent associated disease (40.8 percent) and the majority of infections were of community origin (67.5 percent). Positivity predominated in samples taken from skin lesions and blood cultures with 50.8 percent and 19.2 percent, respectively. Low sensitivity to vancomycin (49.2 percent) and cotrimoxazole (38.3 percent) was evidenced. Conclusions: Staphylococcus aureus infections were more frequent in geriatric male patients of out-of-hospital origin. The germ showed high resistance to antibiotics and of these, the aminoglycosides showed the highest antimicrobial sensitivity(AU)

Presence of Toll Like Receptor-2 in spleen, lymph node and thymus of Swiss albino mice and its modulation by Staphylococcus aureus and bacterial lipopolysaccharide.

Toll-like receptors (TLR) are a family of pattern recognition receptors identifying pathogen associated molecular patterns (PAMPs). They play a critical role in the innate immune response during the initial interaction between the infecting microorganism and phagocytic cells. Here, we verified the presence of TLR-2 in spleen, lymph node and thymus of Swiss albino mice and their modulation after infection with Staphylococcus aureus and Lipopolysaccharide (LPS) challenge. It was seen that TLR-2 gene transcribed to its respective mRNA on S. aureus infection, in thymus, spleen and lymph node of mice but their levels and mode of expression varied. When challenged with LPS no prominent changes in the expression of TLR-2 receptor was observed but its expression increased gradually with time in the thymus, spleen and lymph node of S. aureus infected mice. TLR-2 expression was also found enhanced in infected splenic macrophages. By studying the serum cytokine profile the functionality of the receptor was measured. The results indicate the presence of TLR-2 in thymus, spleen and lymph node of Swiss albino strain of mice and that they are modulated by S. aureus.

Reduced susceptibility to vancomycin and biofilm formation in methicillin-resistant Staphylococcus epidermidis isolated from blood cultures

This study aimed to correlate the presence of ica genes, biofilm formation and antimicrobial resistance in 107 strains of Staphylococcus epidermidis isolated from blood cultures. The isolates were analysed to determine their methicillin resistance, staphylococcal cassette chromosome mec (SCCmec) type, ica genes and biofilm formation and the vancomycin minimum inhibitory concentration (MIC) was measured for isolates and subpopulations growing on vancomycin screen agar. The mecA gene was detected in 81.3% of the S. epidermidis isolated and 48.2% carried SCCmec type III. The complete icaADBC operon was observed in 38.3% of the isolates; of these, 58.5% produced a biofilm. Furthermore, 47.7% of the isolates grew on vancomycin screen agar, with an increase in the MIC in 75.9% of the isolates. Determination of the MIC of subpopulations revealed that 64.7% had an MIC ≥ 4 μg mL-1, including 15.7% with an MIC of 8 μg mL-1 and 2% with an MIC of 16 μg mL-1. The presence of the icaADBC operon, biofilm production and reduced susceptibility to vancomycin were associated with methicillin resistance. This study reveals a high level of methicillin resistance, biofilm formation and reduced susceptibility to vancomycin in subpopulations of S. epidermidis. These findings may explain the selection of multidrug-resistant isolates in hospital settings and the consequent failure of antimicrobial treatment.

Farmacocinética de vancomicina en niños hospitalizados en una unidad de paciente crítico / Pharmacokinetics of vancomycin in children hospitalized in a critical care unit

Introduction: Monitoring PK/PD of vancomycin with basal and peak serum levels and the area under the curve of drug exposure 24 h/MIC (ABC 24 h/MIC) could optimize the management of children. Objective: To study the PK of vancomycin in children hospitalized in the Pediatric Intensive Care Unit (PICU), assessing PK/PD parameters withABC24 h/MIC. Methods: Retrospective, descriptive study in the PICU (Hospital Luis Calvo Mackenna) between January 2008-March 2010. We included children < 18 years who required antimicrobial treatment with vancomycin for suspected/confirmed staphylococcal infection using a dose of 40 mg/k/day. Plasmatic levels were performed one hour postinfusion and 30 min prior to the next dose. The following PK/PD parameters were calculated: vancomycin clearance, elimination rate constant, volume of distribution, half-life (T1/2) and ABC 24 h/ MIC. Results: We enrolled eighty-four children. According to ABC 24 h/MIC obtained, 54% (45/84) of children reached an optimal level (> 400 mg*hr/L). Based on the traditional PK/PD parameters, 49% of cases (41/84) presented a basal level of vancomycin in the therapeutic range (5-15 μg/mL) and of those, only 39% (16/41) had a ABC 24 h/MIC over 400 mg*h/L. Discussion: Based on our results, children admitted to PICU could be exposed to sub therapeutic doses of vancomycin. We recommend to implement tailored antimicrobial treatment monitoring vancomycin PK/PD parameters.

Introducción: El monitoreo farmacocinético-farmacodinámico (PK/PD) de vancomicina podría optimizar el manejo de niños que reciben vancomicina y se encuentran en shock séptico grave. Objetivo: Estudiar PK/PD de vancomicina en niños hospitalizados en una unidad de paciente crítico, relacionando parámetros farmacocinéticos (PFC) tradicionales con ABC 24 h/CIM. Material y Método: Estudio retrospectivo, descriptivo, en la Unidad de Paciente Crítico Pediátrico (UPCP) del Hospital Luis Calvo Mackenna en el período enero de 2008 - marzo de 2010. Se incluyeron niños < 18 años tratados con vancomicina por sospecha/confirmación de infección estafilocóccica y recibieron dosis de 40 mg/kg/día. Se midieron concentraciones plasmáticas pico y basales. Los PFC calculados fueron realizados con software de farmacocinética TDMS®. Resultados: Se enrolaron 84 niños. En relación del parámetro ABC 24h/CIM obtenido, 54% (45/84) de los niños alcanzaron niveles óptimos (> 400 mg*h/L). Del análisis por PFC tradicionales, 49% de los casos (41/84) presentó concentraciones basales de vancomicina en rango terapéutico (5-15 μg/mL) y de ellos, sólo 39% (16/41) presentó un ABC 24 h/CIM > 400 mg*h/L. Todos los pacientes con concentraciones basales > 15 μg/mL alcanzan un ABC 24 h/CIM > 400 mg*h/L. Discusión: Los pacientes pediátricos que ingresan a la UPCP podrían estar expuestos a dosis sub-terapéuticas de vancomicina. Es recomendable individualizar el tratamiento de vancomicina utilizando monitoreo con parámetros PK/PD.

Discontinuation of antimicrobials and costs of treating patients with infection / Descalonamento antimicrobiano y costos con el tratamiento de pacientes con infecciones

OBJECTIVE: To evaluate the repercussions of discontinuation the cost with the antimicrobial treatment of patients with bloodstream infection. METHODS: A historical cohort study conducted in the intensive care unit of a hospital in Belo Horizonte (MG). The population included 62 patients with bloodstream infection caused by Staphylococcus aureus. Data were collected between March/2007 and March/2011 from patients' medical records, Commission of Hospital Infection Control and Sector of Costs, with descriptive and univariate analysis. RESULTS: Colonization was associated with the occurrence of infection with resistant microorganisms (p <0.05). The antimicrobial discontinuation reduced the spectrum of action of the antibiotic prescribed, and the treatment costs (R$ 2,673.12 to R$ 727.03, p = 0.001). CONCLUSION: The discontinuation of antimicrobials favored the redirection of patient therapy, reducing, where necessary, the spectrum of action of the prescribed antimicrobial and, consequently, the costs of treatment.

OBJETIVO: Avaliar as repercussões do descalonamento nos custos com o tratamento antimicrobiano de pacientes com infecção da corrente sanguínea. MÉTODOS: Estudo de coorte histórica realizado em Unidade de Terapia Intensiva de hospital de Belo Horizonte (MG). A população incluiu 62 pacientes com infecção da corrente sanguínea causada por Staphylococcus aureus. Os dados foram coletados entre março/2007 e março/2011 nos prontuários dos pacientes, Comissão de Controle de Infecção Hospitalar e Setor de Custos com análise, descritiva e univariada. RESULTADOS: A colonização esteve associada à ocorrência de infecção por micro-organismo resistente (p<0.05). O descalonamento antimicrobiano reduziu o espectro de ação do antibiótico prescrito e os custos com o tratamento (de R$2.673,12 para R$727,03, p=0,001). CONCLUSÃO: O descalonamento de antimicrobianos favoreceu o redirecionamento da terapia do paciente, reduzindo, quando necessário, o espectro de ação do antimicrobiano prescrito e, consequentemente, os custos com o tratamento.

OBJETIVO: Evaluar las repercusiones del desescalamiento en los costos con el tratamiento antimicrobiano de pacientes con infección de la corriente sanguínea. MÉTODOS: Estudio de cohorte histórica realizado en una Unidad de Terapia Intensiva de un hospital de Belo Horizonte (MG). La población incluyó a 62 pacientes con infección de la corriente sanguínea causada por Staphylococcus aureus. Los datos fueron recolectados entre marzo/2007 y marzo/2011 en las historias clínicas de los pacientes, Comisión de Control de Infección Hospitalaria y Sector de Costos con análisis, descriptivo y univariado. RESULTADOS: La colonización estuvo asociada a la ocurrencia de infección por microorganismo resistente (p<0.05). El desescalamiento antimicrobiano redujo el espectro de acción del antibiótico prescrito y los costos con el tratamiento (de R$2.673,12 para R$727,03, p=0,001). CONCLUSIÓN: El desescalamiento de antimicrobianos favoreció el redireccionamiento de la terapia del paciente, reduciendo, cuando necesario, el espectro de acción del antimicrobiano prescrito y, consecuentemente, los costos con el tratamiento.

Analysis of Methicillin Resistance among Staphylococcus aureus Blood Isolates in an Emergency Department

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has become of great concern in both hospital and community settings. To evaluate the prevalence and risk factors for methicillin resistance among Staphylococcus aureus, blood isolates in our Emergency Department (ED) were collected. All patients with S. aureus bacteremia (SAB) who presented to the ED from January 2000 to August 2005 were included, and a retrospective study was performed. A total of 231 patients with SAB were enrolled (median age, 59 yr; M:F, 125:106). Among these patients, methicillin-resistant strains accounted for 27.3% (63 patients). Catheter-related infection was the most frequent primary site of SAB (39.0%), followed by skin and soft tissue infection (16.5%). In multivariate analysis, recent surgery (OR, 3.41; 95% CI, 1.48-7.85), recent hospitalization (2.17; 1.06-4.62), and older age (> or =61 yr) (2.39; 1.25-4.57) were independently associated with the acquisition of methicillin-resistant strains. When antimicrobial therapy is considered for the treatment of a patient with suspected SAB, clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage for patients with risk factors: older age, recent hospitalization, and recent surgery.

Coagulase negative Staphylococci from blood cultures: contaminants or pathogens? / Estafilococos Coagulasa-Negativos de Cultivos de Sangre: ¿Contaminantes o Patógenos?

Detailed clinical data, underlying conditions, inflammatory indices and microbiological parameters in 60 patients who had pure growth of coagulase negative staphylococci from their blood culture specimens at the University Hospital of the West Indies, Jamaica, were analyzed and the clinical significance of the isolates ascertained using standard criteria. This study was undertaken between April and September 2003. The isolates were true pathogens of bloodstream infections in only 5 of the 60 patients (8.4). In the vast majority ie 44 of 60 (73.3) they were mere blood culture contaminants and in 11 (18.3), the clinical significance could not be ascertained Fifteen of the 44 patients (34) with contaminating coagulase negative staphylococci were treated with specific anti-staphylococcal antibiotics; 5 (11.4) with vancomycin. Although there has been a relative increase of coagulase negative staphylococcal infections including bloodstream infections in recent years, the organisms still remain the most common contaminants in blood cultures. Over 70of isolates were contaminants in this study which is similar to that in a number of such studies in other parts of the world The findings underline the need for careful evaluation of coagulase negative staphylococci isolated from blood cultures before instituting therapy to avoid unnecessary use of antibiotics, especially vancomycin, and the consequent increase of antibiotic resistance in hospitals.

Los datos clínicos detallados, las condiciones subyacentes, los índices inflamatorios así como los parámetros microbiológicos de 60 pacientes que presentaron crecimiento puro de estafilococos coagu-lasa-negativos de sus cultivos de sangre en el Hospital Universitario de West Indies, Jamaica, fueron sometidos a análisis. De este modo, se pudo determinar la significación clínica de los aislados, usando criterios estándar. En sólo 5 de los 60 pacientes (8.4%), los aislados resultaron ser realmente pató-genos de infecciones del torrente sanguíneo. En la gran mayoría, a saber 44 de 60 (73.3%), se trataba tan sólo de contaminantes en el cultivo de la sangre, y en 11 (18.3%) no pudo determinarse la impor-tancia clínica. Quince de los 44 pacientes (34%) con estafilococos coagulasa-negativos contaminantes, fueron tratados con antibióticos antiestafilocócicos específicos, y 5 (11.4%) con vancomicina. Aunque en años recientes ha habido un aumento relativo de infecciones por estafilococos coagulasa-negativos – incluyendo infecciones del torrente sanguíneo – los organismos siguen siendo todavía los contamin-antes más comunes en los cultivos de sangre. Más del 70% de los aislados resultaron ser contaminantes en este estudio: un resultado similar al obtenido en una serie de estudios de este tipo realizado en otras partes del mundo. Los hallazgos apuntan a la necesidad de realizar una evaluación cuidadosa de los estreptococos coagulasa-negativos aislados en los cultivos de sangre antes de proceder a instituir la terapia, a fin de evitar el uso innecesario de antibióticos – en especial la vancomicina – y el consiguiente aumento de la resistencia antibiótica en los hospitales.

Epidemiology of coagulase-negative Staphylococci isolated from clinical blood specimens at the University Hospital of the West Indies / Epidemiología de los Estafilococos Coagulasa Negativos Aislados de Especímenes Clínicos de Sangre en el Hospital Universitario de West Indies

The prevalence and significance of coagulase negative staphylococci (CoNS) isolated from blood cultures at the University Hospital of the West Indies (UHWI) during a six-month period were investigated. Standard and automated microbiological procedures were used to process 3001 blood culture specimens received from 2363 patients and 658 (21.9) of the blood cultures yielded 854 bacterial isolates. The highest prevalence of positive blood cultures (60) and the lowest prevalence of blood isolates of CoNS (12) were found in the intensive care unit (ICU). The blood isolates of CoNS were most frequent in the surgical wards (13) and lowest in obstetrics and gynaecology (2). High rates of resistance to methicillin, other anti-staphylococcal penicillins, and cephalosporins used in the treatment of CoNS were observed All blood isolates of CoNS (100) were susceptible to vancomycin. In conclusion, the results show that coagulase-negative staphylococci are the most prevalent bacterial isolates in blood cultures at the UHWI occurring mostly as contaminants. The practice of proper venepuncture and hand-washing techniques by medical staff are recommended to facilitate appropriate antibiotic usage.

Se investigó la prevalencia e importancia de los estafilococos coagulasa negativos (ECoN) aislados de cultivos de sangre en el Hospital Universitario de West Indies (HUWI) por un período de seis meses. Se utilizaron procedimientos microbiológicos estándar y automatizados para procesas 3001 cultivos de sangre recibidos de 2363 pacientes y 658 (21.9%) de los cultivos dieron 854 aislados bacterianos. La más alta prevalencia de cultivos de sangre positivos (60%) y la más baja prevalencia de aislados de ECoN (12%) se encontraron en la Unidad de Cuidados Intensivos (UCI). Los aislados de sangre de ECoN fueron más frecuentes en las salas de cirugía (13%) y más bajos en las de obstetricia y ginecología (2%). Se observaron altas tasas de resistencia a la meticilina, así como a otras penicilinas anti-estafilocócicas y cefalosporinas usadas en el tratamiento de ECoN. Todos los aislados de sangre de ECoN (100%) fueron susceptibles a la vancomicina. En conclusión, los resultados muestran que los estafilococos coagulasa negativos son los aislados bacterianos más prevalentes en cultivos de sangre en el HUWI, presentándose en la mayor parte de los casos como contaminantes. Se recomienda la práctica de técnicas adecuadas de venepuntura y lavado de manos por parte del personal médico a fin de facilitar un uso antibiótico correcto.

Comparative chemotherapeutic efficacy of balhimycin, desgluco-balhimycin against experimental MSSA and MRSA infection in mice.

Balhimycin and desglucobalhimycin are glycopeptide antibiotics isolated from an Amycolatopsis spp during the search for novel antibacterials against MRSA from the natural product screening at the Research Centre of formerly Hoechst India Ltd. in Bombay, India. Both compounds show excellent in vitro activity against methicillin sensitive and resistant Staphylococcus aureus (MSSA, MRSA). Both compounds were also found to be active against a number of MRSA strain in the animal studies. The activities were comparable to that of the reference glycopeptides vancomycin and teicoplanin used in these studies. Teicoplanin displayed better in vivo efficacy against S. epidermidis 4929H and Streptococcus pyogenes A77 than either vancomycin or desgluco-balhimycin in the present study. Preliminary studies on pharmacokinetic and acute toxicity were done to get some idea at the early stage of the investigation about the promise of the compounds for development.

Incidence of methicillin resistant coagulase positive & coagulase negative staphylococci in blood cultures.

Isolates of Staphylococcus aureus and coagulase negative staphylococci (CONS) from blood culture of bacteraemic patients were studied for methicillin resistance is 1993 and 1996. An increase in methicillin resistance among these isolates was observed in 1996. In 1993, 32.6 per cent isolates of S. aureus were methicillin resistant, this increased to 45.7 per cent in 1996. Methicillin resistance in CONS were 1.6 and 14.6 per cent respectively in 1993 and 1996. This increase in methicillin resistance may pose therapeutic problems and requires more effective drugs based on susceptibility testing of such isolates.

Determination of teichoic acid antibody for the diagnosis of pediatric staphylococcal infections.

Determination of teichoic acid antibodies by Enzyme-linked Immunosorbent Assay (ELISA) was done in 39 patients with Staphylococcus aureus infections and 151 patients who did not have a history of serious staphylococcal infections. The latter who were treated for other diseases served as controls. Various levels of teichoic acid antibodies below 1:3,200 were detected in controls while significantly higher levels were seen in patients with Staphylococcus aureus infections.

Evaluation of ceruloplasmin in neonatal septicemia.

Serial serum ceruloplasmin (Cp) levels were estimated in healthy and septicemic neonates, using single radial immunodiffusion. In 25 healthy neonates mean Cp levels were 19.82 mg/dl at birth, 18.20 mg/dl at 12-24 hours, 17.26 mg/dl at 14 +/- 4 days and 17.68 mg/dl at 28 +/- 4 days of life. For the entire neonatal period the mean Cp levels were computed to be 18.24 mg/dl. In 20 culture positive, septicemic neonates, mean Cp levels were 27 mg/dl at onset of disease, 28.65 mg/dl 12-24 hours later and 36.2 mg/dl after 7 +/- 3 days of start of illness (p less than 0.001 for all sampling intervals as compared to healthy group values in first month of life). The mean Cp levels were unaffected by gestational age in both groups. In the septicemic neonates, the mean Cp levels in dying neonates did not differ significantly from recovering neonates for all sampling intervals. It is concluded that estimation of serum Cp levels may help in diagnosis of neonatal septicemia, but it is not useful as an early diagnostic aid or for prognostication.

Pyogenic meningitis.

Fifty cases with pyogenic meningitis, aged 15 to 72 years, with a male:female ratio of 5:1, were studied. The majority of cases (70%) were in the 15 to 25 years age group. The organisms detected in the 29 culture-positive cases included S aureus (12), pneumococci (9) and meningococci (8). Thirteen patients died; the poor prognostic factors included old age, the presence of coma or shock, CSF sugar below 10 mg/dl or protein above 750 mg/dl and the presence of gram negative organisms in the CSF.