Whole-process individualized pharmaceutical care for a case of melioidosis sepsis / 中国药房

OBJECTIVE To provide reference for the adjustment of antibiotic treatment regimens， identification of adverse reactions， and individualized pharmaceutical care for melioidosis sepsis （MS）. METHODS Clinical pharmacists participated in the intensive and eradicating therapeutic processes for an MS patient by using blood concentration and gene detection. Based on the literature， antibiotic treatment regimens of MS were adjusted by determining the blood concentrations of β-lactam and trimethoprim/ sulfamethoxazole （TMP/SMZ） and calculating PK/PD parameters. The causes of adverse drug reactions were analyzed and addressed by detecting drug-related gene polymorphisms through high-throughput sequencing. RESULTS Clinical pharmacists used blood concentration and genetic testing methods to propose adjustments to imipenem-cilastatin sodium dosage and analyze the causes of various adverse drug reactions. PK/PD targets were calculated by measuring the blood concentrations of β-lactam and TMP/SMZ. Clinical pharmacists explained to clinical doctors the compliance status of patients with melioidosis in sepsis and non- sepsis stages through reviewing guidelines and literature； the results of blood concentration and genetic test were used to analyze the correlation of neurotoxicity of MS patients with B14） IMP cmin， and it was found that nephrotoxicity was not related to the cmax of TMP/SMZ， but to the patient’s water intake. After whole-process antibiotic treatment， the patient’s condition improved and was discharged， and the adverse reactions were effectively treated. CONCLUSIONS Clinical pharmacists use blood concentration and genetic tests to assist clinicians in formulating MS treatment regimens， and provide whole-course pharmaceutical care for a MS patient. This method has improved the safety and effectiveness of clinical drug therapy.

Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug

ABSTRACT Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

Application of prone position in severe ARDS caused by pneumocystis jirovecii pneumonia after kidney transplantation / 器官移植

Objective To investigate the improvement of oxygenation after the treatment of prone position in patients with severe acute respiratory distress syndrome (ARDS) caused by pneumocystis jirovecii pneumonia (PJP) after kidney transplantation. Methods Clinical data of 5 cases of moderate and severe ARDS caused by PJP after kidney transplantation were analyzed retrospectively, and clinical characteristics, treatment regimen and prognosis were summarized. Results Clinical manifestations of 5 patients were fever, dry cough, chest tightness, shortness ofbreath,sweating and fatigue, and body temperature fluctuated between 38 ℃ and 39 ℃, percutaneous arterial oxygen saturation(SpO2) was gradually decreased, and respiratory distress symptoms were worsened. Pulmonary CT scan showed diffuse ground-glass shadow. After transfer to intensive care unit (ICU), immunosuppressive drugs were terminated, and all patients were given with compound sulfamethoxazole, caspofungin, low-dose glucocorticoids against pneumocystis jirovecii (PJ), oxygen therapy and other symptomatic supportive treatments. Four patients diagnosed with severe ARDS upon admission to ICU were treated in a prone position. One patient with moderate ARDS was not kept in a prone position. At 1 d after treatment in a prone position, partial pressure of arterial oxygen (PaO2) and oxygenation index were increased, whereas alveolar-arterial oxygen difference (A-aDO2) was decreased compared with before treatment (allP<0.05). Compared with 1 d after treatment, SpO2, PaO2 and oxygenation index were all increased, while A-aDO2 was decreased at 4 d after treatment (all P<0.05). Box diagram showed that oxygenation index showed an overall upward trend after prone-position treatment, whereas A-aDO2 showed an overall downward trend. The length of ICU stay of 5 patients was 14 (8, 29) d. All patients in a prone position did not develop complications, such as skin pressure sore, tube detachment and tube displacement, etc. Among 5 patients, 4 patients were mitigated, and 1 patient died of septic shock and multiple organ failure. Conclusions For both conscious and intubated patients, a prone position may significantly improve oxygenation and prognosis of patients with severe ARDS caused by PJP after kidney transplantation. Early diagnosis and accurate and standardized treatment play a pivotal role in enhancing cure rate.

Efficacy and safety of trimethoprim/sulfamethoxazole combined with caspofungin for the treatment of acquired immunodeficiency syndrome patients with moderate to severe pneumocystis pneumonia / 中华传染病杂志

Objective:To assess the efficacy and safety of trimethoprim/sulfamethoxazole (TMP/SMZ) combined with caspofungin for the treatment of acquired immunodeficiency syndrome (AIDS)patients with moderate to severe pneumocystis pneumonia (PCP) requiring mechanical ventilation.Methods:The clinical data of AIDS patients who admitted to Chongqing Public Health Medical Center from March 1, 2019 to March 1, 2021 with moderate to severe PCP requiring mechanical ventilation were retrospectively analyzed. Clinical characteristics and outcomes were compared between two groups receiving either combination therapy with TMP/SMZ and caspofungin (combination therapy group) or TMP/SMZ monotherapy (monotherapy group). The patients were divided into two subgroups according to the baseline arterial partial pressure of oxygen (PaO 2), patients with arterial PaO 2≥50 mmHg (1 mmHg=0.133 kPa) and PaO 2 <50 mmHg. The clinical efficacies of combination therapy and monotherapy in each subgroup were further compared. Chi-square and Fisher exact test were used for statistical analysis. The three-month survival was estimated by the Kaplan-Meier method, and the three-month survival rates were compared by Log-rank method. Results:A total of 83 patients were enrolled, including 23 in the monotherapy group and 60 in the combination therapy group. There was no significant difference in all-cause hospital mortalities between these two groups (34.8%(8/23) vs 23.3%(14/60), χ2=1.12, P=0.290). Kaplan-Meier survival curves indicated no significant difference in the three-month survival rates between the two groups ( χ2=0.51, P=0.477). There ware no significant differences observed in the positive clinical response rates and the mechanical ventilation rates after seven days of anti-PCP treatment between the two groups ( χ2=0.02 and 0.01, respectively, both P>0.05). In the 52 patients with PaO 2≥50 mmHg, no significant difference in all-cause hospital mortalities was observed between the monotherapy group and the combination therapy group (2/13 vs 25.6%(10/39), χ2=0.14, P=0.704). There was no statistical significance in the three-month survival rates between the two groups ( χ2=0.69, P=0.407). No significant difference was observed either in the clinical positive response rates or the mechanical ventilation rates after seven days of anti-PCP treatment between the two group( χ2=1.02 and 0.69, respectively, both P>0.05). In the 31 patients with PaO 2<50 mmHg, the all-cause hospital mortality in the combination therapy group was 19.0%(4/21), while six of the 10 patients in the monotherapy group died, and the difference was statistically significant (Fisher exact test, P=0.040). The three-month survival rate in the combination therapy group was significantly higher than that in the monotherapy group ( χ2=4.09, P=0.043). There were no significant differences in clinical positive response rate and the mechanical ventilation rate after seven days of anti-PCP treatment between the two group (Fisher exact test, both P>0.05). The overall adverse event rate in the monotherapy group was 87.0%(20/23), with an incidence of 56.5%(13/23) for both electrolyte disturbances and bone marrow suppression. The above incidences in the combination therapy group were 78.3%(47/60), 35.0%(21/60) and 53.3%(32/60), respectively, and all differences were not statistically significant ( χ2=0.34, 3.18 and 0.07, respectively, all P>0.05). Conclusions:The efficacy of combination therapy with TMP/SMZ and caspofungin is comparable to that of TMP/SMZ monotherapy in AIDS patients with moderate to severe PCP requiring mechanical ventilation. However, in AIDS patients with PCP requiring mechanical ventilation with the baseline PaO 2<50 mmHg, the efficacy of combination therapy is statistically superior to that of TMP/SMZ monotherapy. Combination therapy does not increase the risk of adverse events.

INCIDENCE OF TRIMETHOPRIM-SULFAMETHOXAZOLE RESISTANT S. MALTOPHILIA INFECTIONS IN A MEXICO CITY HOSPITAL

Introduction: Stenotrophomonas maltophilia is a non-fermentative gram-negative bacillus with increasing importance as a multidrug-resistant nosocomial agent. Despite reports of mortality rates between 14 and 69% in patients with bacteremia, the information documented in our environment is minimal. Methods: Descriptive, observational, retrospective and longitudinal study. Outpatients and hospitalized patients were sampled between January 1 and December 31, 2019, from the Centro Médico Nacional siglo XXI. Bacterial growth was evaluated to identify the presence of S. maltophilia. In a total of 7,019 cultures, we observed a frequency of 94 cases of S. maltophilia and in Results: these we identi?ed that 54.5% were resistant to trimethoprim-sulfamethoxazole. Women were the most affected by this entity with a median age of 54.5 years. Fifty percent of the samples came from intensive therapy and the most frequent site of extraction was the trachea. We identi?ed a higher resistance to trimethoprim-sulfamethoxazole than that reported in the Discussion: literature (5%), in an organism capable of developing both nosocomial and community-acquired infections, forcing us to suspect its existence as well as a second treatment option in the face of multidrug resistance

Hipercalemia asociada a la administración de trimetoprima y sulfametoxazol

Introducción la trimetoprima y el sulfametoxazol es una combinación de agentes antimicrobianos, con su uso se han descrito algunas reacciones adversas, entre las que están las alteraciones electrolíticas como la hipercalemia. Objetivo la revisión de este caso se propone como una estrategia que permite proveer herramientas al personal de salud para la detección de un evento adverso como la hipercalcemia asociada a la administración de trimeoprim sulfametoxazol, antimicrobianos ampliamente usados en servicios de urgencias, hospitalización, unidades de cuidados especiales/intensivos e incluso de manera ambulatoria. Presentación de caso se presenta el reporte de un paciente sin los factores de riesgo descritos en la literatura para el desarrollo de hipercalemia, permitiendo a través de su discusión sensibilizar al personal de salud sobre este efecto, siendo además el primer caso reportado en nuestro medio en un paciente menor de 50 años. Discusión y conclusión Desde 1983 se registran los primeros casos de hipercalcemia asociados a la administración de estos antimicrobianos, describiéndose diferentes factores de riesgo como la edad, la coexistencia de insuficiencia renal, el uso de diuréticos ahorradores de potasio, antihipertensivos inhibidores de la enzima convertidora de angiotensina y receptores de angiotensina 2, si bien es importante vigilar estrechamente a estos grupos de riesgo, este evento puede presentarse también en ausencia de los mismos, como en el caso de este paciente.

Introduction Trimethoprim and sulfamethoxazole is a combination of antimicrobial agents, with its use some adverse reactions have been described, including electrolyte disturbances such as hyperkalemia. Purpose The review of this case is proposed as a strategy that allows providing iper to health personnel for the detection iper adverse iperc such as ipercalcemia associated with the administration of trimeoprim sulfamethoxazole, antimicrobials widely used in emergency services, hospitalization, special/intensive care units and even on an outpatient basis. Case presentation A patient case report is presented without the additional risk factors described in the literature for the development of hyperkalemia, allowing through its discussion to sensitize health personnel about this effect, also being the first case reported in our environment in a patient under 50 years old. Discussion and conclusion Since 1983, the first cases of hypercalcaemia associated with the administration of these antimicrobials have been recorded, describing different risk factors such as age, the coexistence of renal failure, the use of potassium-sparing diuretics, antihypertensive inhibitors of the angiotensin-converting enzyme and receptors. Of angiotensin 2, although it is important to closely monitor these risk groups, this event can also occur in their absence, as in the case of this patient.

Dermatosis Pustulosa Subcórnea / Subcorneal pustular dermatosis

RESUMEN La dermatosis pustulosa subcórnea o enfermedad de Sneddon Wilkinson, es una enfermedad poco frecuente, caracterizada por lesiones pustulosas, recurrentes que suelen coalescer. Esta afección también se relaciona con enfermedades neoplásicas o inmunológicas. El propósito de este estudio es describir un caso clínico de ladermatosis referida en una paciente de 54 años de edad inicialmente tratada con dapsona, aunque,si bien, durante dos meses hubo mejoría, posteriormente se observa desarrollo de nuevas lesiones y alteración de las transaminasas. Por este motivo se procede a cambiar de tratamiento, por trimetoprima /sulfametoxazol.

Abstract Subcorneal pustular dermatosis or Sneddon Wilkinson's disease is a rare disease characterized by recurrent pustular lesions that often coalesce. This condition is also associated with neoplastic or immunologic diseases. The purpose of this study is to describe a clinical case of the referred dermatosis in a 54-year-old female patient initially treated with dapsone, although there was improvement for two months, subsequently new lesions developed and transaminase alteration was observed, for this reason the treatment was changed to trimethoprim/sulfamethoxazole.

Hipersensibilidad al trimetoprim + sulfametoxazol en un paciente con osteomielitis en esquema de desensibilización

Introducción: La osteomielitis es una inflamación del tejido óseo, la cual puede ser causada por un agente infeccioso de tipo Gram positivo como Gram negativo, generalmente ocasionado por Staphylococcus aureus; esta infección usualmente es tratada con trimetoprim + sulfametoxazol, desafortunadamente durante el tratamiento pueden aparecer reacciones adversas a medicamentos de tipo alérgicas, lo que implicaría un cambio de antibiótico o someter al paciente a esquema de desensibilización. Objetivo: Reportar el caso de un paciente que fue sometido a dicho esquema, empleando la vía intravenosa. Resultados: Paciente masculino de 14 años de edad ingresó a la institución con osteomielits de tibia derecha en su posoperatorio de osteosintesis realizado dos meses antes. Se decidió iniciar tratamiento con TMP-SMX 300 mg intravenoso (IV) cada 12 horas. Se informó al paciente y ya que era menor de edad, a su familiar a cargo sobre la importancia del procedimiento, posibles riesgos y beneficios mediante consentimiento informado por escrito. El paciente presentó una erupción cutánea acompañada de prurito en el pecho y espalda, lo cual fue tratado y solucionado, por consiguiente se dispuso a someter al paciente al esquema para su desensibilización el cual fue realizado empleando el medicamento en solución inyectable (trimetoprim + sulfametoxazol 400 mg + 80 mg/5 mL) para dar continuidad a su tratamiento, además el paciente fue monitorizado y no se le administró tratamiento con antihistamínicos o corticoides para así evitar una respuesta errónea o resultados falsos/positivos durante el procedimiento. Conclusión: El paciente fue desensibilizado con éxito para continuar con su tratamiento farmacológico. Este caso reportado puede contribuir a modificar los esquemas de desensibilización actuales, el esquema de desensibilización es una herramienta muy útil para continuar el tratamiento farmacológico en pacientes con hipersensibilidad al TMP/SMX, sin necesidad de optar por otras alternativas terapéuticas que podrían ser menos eficaces para el control de la infección.

SUMMARY Introduction: Osteomyelitis is an inflammation of the bone tissue, which can be caused by a Gram-positive or Gram-negative infectious agent, generally caused by Staphylococcus aureus. This infection is usually treated with trimethoprim + sulfamethoxazole. Unfortunately, adverse drug reactions of the allergic type may appear during treatment, which would imply a change of antibiotic or subject the patient to a desensitization scheme. Objective: To report the case of a patient who underwent this scheme, using the intravenous route. Results: A 14-year-old male patient was admitted to the institution with osteomyelitis of the right tibia in his postoperative period of osteosynthesis performed two months earlier. It was decided to start treatment with TMP-SMX 300 mg intravenously (IV) every 12 hours. The patient and, since he was a minor, his dependent relative were informed about the importance of the procedure, possible risks and benefits through written informed consent. The patient presented a skin rash accompanied by itching on the chest and back. which was treated and resolved, therefore, the patient was submitted to the scheme for his desensitization, which was carried out using the medicine in injectable solution (trimethoprim + sulfamethoxazole 400 mg + 80 mg/5 mL) to continue his treatment, In addition, the patient was monitored and treatment with antihistamines or corticosteroids was not administered in order to avoid an erroneous response or false/positive results during the procedure. Conclusion: The patient was successfully desensitized to continue with his pharmacological treatment. This reported case can contribute to modify the current desensitization schemes; the desensitization scheme is a very useful tool to continue pharmacological treatment in patients with hypersensitivity to TMP/SMX, without the need to opt for other therapeutic alternatives that could be less effective for infection control.

Introdução: A osteomielite é uma inflamação do tecido ósseo, que pode ser causada por um agente infeccioso Gram-positivo ou Gram-negativo, geralmente causado por Staphylococcus aureus; essa infecção geralmente é tratada com trimetoprima + sulfametoxazol, mas infelizmente, durante o tratamento, podem surgir reações adversas medicamentosas do tipo alérgico, o que implicaria na troca de antibiótico ou submeter o paciente a um esquema de dessensibilização. Objetivo: Relatar o caso de um paciente submetido a esse esquema, pela via intravenosa. Resultados: Um paciente do sexo masculino de 14 anos foi admitido na instituição com osteomielite da tíbia direita em pós-operatório de osteossíntese realizada há dois meses. Optou-se por iniciar o tratamento com TMP-SMX 300 mg por via intravenosa (IV) a cada 12 horas. O paciente e, por ser menor de idade, seu familiar dependente foram informados sobre a importância do procedimento, possíveis riscos e benefícios por meio do termo de consentimento livre e esclarecido. O paciente apresentou erupção cutânea acompanhada de coceira no tórax e nas costas, que foi tratado e resolvido, portanto, o paciente foi submetido ao esquema para sua dessensibilização, que foi realizada utilizando o medicamento em solução injetável (trimetoprim + sulfa-metoxazol 400 mg + 80 mg/5 mL) para continuar seu tratamento. o paciente foi monitorado e não foi administrado tratamento com anti-histamínicos ou corticos-teróides para evitar resposta errônea ou resultados falsos/positivos durante o procedimento. Conclusão: O paciente foi dessensibilizado com sucesso para continuar com seu tratamento farmacológico. Este caso relatado pode contribuir para modificar os esquemas de dessensibilização atuais, o esquema de dessensibilização é uma ferramenta muito útil para continuar o tratamento farmacológico em pacientes com hipersensibilidade ao TMP/SMX, sem a necessidade de optar por outras alternativas terapêuticas que poderiam ser menos eficazes para o controle de infecção.

Simultaneous determination of sulfamethoxazole, trimethoprim and bromhexine in veterinary formulation using high performance liquid chromatography (HPLC)

Objetivo: desarrollar y validar un método simple, sensible y rápido para la determinación simultánea de sulfametoxazol (SMT), trimetoprima (TMP) y bromhexina (BMX) en formulación veterinaria por cromatografía líquida de alta resolución de acuerdo con las directrices de validación y control. Guía para la calidad analítica de medicamentos en productos alimenticios y medicamentos veterinarios, RDC 166/2017 y guías internacionales Conferencia Internacional sobre Armonización y Asociación Internacional de Químicos Analíticos Oficiales. Materiales y métodos: la separación se realizó en una columna analítica ThermoScientific® C18 AcclaimTM120 (4,6 x 250 mm, 5 µm), con caudal de 0,7 mL min-1 y detección a 245 nm, 265 nm y 271 nm, para BMX, SMT y TMP, respectivamente. Todas las mediciones se realizaron en metanol:agua (84:16 v/v; pH 3,0). Las curvas analíticas fueron lineales (r > 0,9997) en el rango de concentración de 15.0 a 30.0 µg-mL-1 para SMT, 3.0 a 9.0 µg-mL-1 para TMP y 0,5 a 2,0 µg-mL-1 para BMX. Resultados: el método demostró ser preciso con coeficientes de variación por debajo del límite máximo de 2,0%, robusto, sin influencia significativa de las variaciones utilizadas en el análisis, exacto (recuperación >99%) y selectivo, en la evaluación de la interferencia de adyuvantes Conclusión: por lo tanto, el método desarrollado demostró ser adecuado para los análisis de control de calidad de rutina para la determinación simultánea de SMT, TMP y BMX en formulaciones farmacéuticas.

SUMMARY Aim: To develop and to validate a simple, sensitive and fast method for the simultaneous determination of sulfamethoxazole (SMT), trimethoprim (TMP) and bromhexine (BMX) in veterinary formulation by high performance liquid chromatography according to the guidelines of the Validation and Control Guide for analytical quality of medicines in food products and veterinary medicines, RDC 166/2017 and international guides International Conference on Harmonization and International Association of Official Analytical Chemists. Materials and methods: The separation was performed on a ThermoScientific® C18 AcclaimTM120 analytical column (4.6 X 250 mm, 5 µm), with a flow rate of 0.7 mL min-1 and detection at 245 nm, 265 nm and 271 nm, for BMX, SMT and TMP, respectively. All measurements were performed in methanol: water (84:16 v/v; pH 3.0). The analytical curves were linear (r > 0.9997) in the concentration range of 15.0 to 30.0 µg-mL-1 for SMT, 3.0 to 9.0 µg-mL-1 for TMP and 0.5 to 2.0 µg-mL-1 for BMX. Results: The method proved to be accurate, with coefficients of variation below the maximum limit of 2.0%, robust, without significant influence of the variations used in the analysis, exact (recovery >99%) and selective, in the assessment of interference from adjuvants. Conclusion: Therefore, the developed method proved to be suitable for routine quality control analyzes for the simultaneous determination of SMT, TMP and BMX in pharmaceutical formulations.

Objetivo: desenvolver e validar um método simples, sensível e rápido para a determinação simultânea de sulfametoxazol (SMT), trimetoprima (TMP) e bromexina (BMX) em formulação veterinária por cromatografia líquida de alta eficiência de acordo com as diretrizes do Validation and Control Guia de qualidade analítica de medicamentos em produtos alimentícios e medicamentos veterinários, RDC 166/2017 e guias internacionais Conferência Internacional de Harmonização e Associação Internacional de Químicos Analíticos Oficiais. Materiais e métodos: a separação foi realizada em coluna analítica ThermoScientific® C18 AcclaimTM120 (4,6 X 250 mm, 5 µm), com vazão de 0,7 mL min-1 e detecção em 245 nm, 265 nm e 271 nm, para BMX , SMT e TMP, respectivamente. Todas as medições foram realizadas em metanol:água (84:16 v/v; pH 3,0). As curvas analíticas foram lineares (r > 0,9997) na faixa de concentração de 15,0 a 30,0 µg-mL-1 para SMT, 3,0 a 9,0 µg-mL-1 para TMP e 0,5 a 2,0 µg-mL-1 para BMX. Resultados: o método mostrou-se preciso, com coeficientes de variação abaixo do limite máximo de 2,0%, robusto, sem influência significativa das variações utilizadas na análise, exato (recuperação >99%) e seletivo, na avaliação da interferência de adjuvantes. Conclusão: portanto, o método desenvolvido mostrou-se adequado para análises de controle de qualidade de rotina para a determinação simultânea de SMT, TMP e BMX em formulações farmacêuticas.

Retinocoroiditis toxoplásmica y la evolución del resultado visual en pacientes inmunocompetentes / Toxoplasmic retinochoroiditis and the evolution of visual results in immunocompetent patients

Objetivo: Determinar la evolución del resultado visual en pacientes con toxoplasmosis ocular activa. Métodos: Se realizó un estudio observacional prospectivo longitudinal en 101 pacientes inmunocompetentes con toxoplasmosis ocular activa, atendidos en la consulta de Uveítis del Hospital General Docente "Abel Santamaría", desde enero de 2012 a diciembre de 2018. Se evaluaron las variables localización de la lesión, tamaño, número, episodio, grado de inflamación, complicaciones, recurrencia postratamiento y mejor agudeza visual corregida. Se analizaron los resultados utilizando frecuencias absolutas y relativas, la asociación estadística chi cuadrado, las pruebas U Mann-Whitney o Kruskall Wallis, Friedman y de rangos con signos de Wilcoxon. Resultados: Según la localización de la lesión, los resultados visuales inferiores se presentaron en los pacientes con lesiones en zona I y los mejores se obtuvieron cuando hubo afectación en zona III. Se mostró una mejor evolución del resultado visual en los que tuvieron lesiones menores o iguales a un diámetro papilar. Existió diferencia estadística entre los diferentes grados de gravedad de la inflamación, con tendencia al incremento de la mejor agudeza visual corregida en el tiempo, después del tratamiento. Conclusiones: Durante la evolución de los pacientes inmunocompetentes con toxoplasmosis ocular activa se logra mejoría de la visión(AU)

Objective: Determine the evolution of visual results in patients with active ocular toxoplasmosis. Methods: An observational longitudinal prospective study was conducted of 101 immunocompetent patients with active ocular toxoplasmosis attending the Uveitis Service at Abel Santamaría General University Hospital from January 2012 to December 2018. The variables evaluated were injury location, size, number, episode, degree of inflammation, complications, post-treatment recurrence and best corrected visual acuity. Results were analyzed with absolute and relative frequencies, chi-square statistical association, the Mann-Whitney U or Kruskall Wallis tests, the Friedman test and the Wilcoxon signed-rank test. Results: According to injury location, the lowest visual results were obtained in patients with zone I lesions, whereas the best results corresponded to zone III lesions. A better visual result evolution was achieved in patients with lesions smaller than or equal to a papillary diameter. A statistical difference was found between the various degrees of inflammation severity, with a tendency to an increase in best corrected visual acuity with the passing of time after treatment. Conclusions: Visual improvement is achieved during the evolution of immunocompetent patients with active ocular toxoplasmosis(AU)

Síndrome de DRESS en una paciente con fibrosis quística: reporte de un caso pediátrico / DRESS syndrome in a patient with cystic fibrosis: a pediatric case report

El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos o síndrome de DRESS según sus siglas en inglés (drug reaction with eosinophilia and systemic symptoms) se encuentra entre las reacciones medicamentosas cutáneas graves. Este consiste en una tríada clínica que incluye fiebre, exantema y compromiso sistémico, acompañado de eosinofilia y/o linfocitos atípicos.Se presenta el caso de una paciente de sexo femenino con fibrosis quística, de 18 meses de edad, quien desarrolló esta patología durante un tratamiento con trimetoprima-sulfametoxazol para erradicar Staphylococcus aureus meticilino resistente en esputo. Los pacientes con fibrosis quística reciben múltiples esquemas antibióticos según bacteriología en secreciones respiratorias para evitar el deterioro de la función pulmonar y colonización por gérmenes resistentes. Es menester conocer y sospechar este síndrome, debido al riesgo incrementado de hipersensibilidad a drogas en fibrosis quística, pronóstico ominoso y su elevada morbimortalidad

Drug reaction with eosinophilia and systemic symptoms or DRESS syndrome is among severe cutaneous drug reactions. This constitutes a clinical triad that includes fever, skin rash and systemic compromise, accompanied by eosinophilia and/or atypical lymphocytes.We present the case of an 18-month-old female patient with cystic fibrosis, who develops this pathology during a trimethoprim-sulfamethoxazole cycle as an eradicating treatment of methicillin-resistant Staphylococcus aureus in bronchial secretions. Cystic fibrosis patients receive multiple antibiotic regimens according to bacteriology in sputum, to avoid impairment in their lung function and colonization by resistant germs. Due to the increased risk of drug hypersensitivity in cystic fibrosis, an ominous prognosis and high morbidity and mortality, knowledge and a high index of suspicion of this syndrome are necessary

Laboratory-based surveillance of Shigella spp. from human clinical cases in Colombia, 1997-2018 / Vigilancia por el laboratorio de Shigella spp. aislada de casos clínicos humanos en Colombia, 1997-2018

Abstract | Introduction: Shigellosis is endemic in low-and middle-income countries, causing approximately 125 million episodes of diarrhea and leading to approximately 160.000 deaths annually one-third of which is associated with children. Objective: To describe the characteristics and antimicrobial resistance profiles of Shigella species recovered in Colombia from 1997 to 2018. Materials and methods: We received isolates from laboratories in 29 Colombian departments. We serotyped with specific antiserum and determined antimicrobial resistance and minimal inhibitory concentrations for ten antibiotics with Kirby-Bauer tests following the Clinical and Laboratory Standards Institute recommendations. Results: We analyzed 5,251 isolates of Shigella spp., most of them obtained from stools (96.4%); 2,511 (47.8%) were from children under five years of age. The two most common species were S. sonnei (55.1%) and S. fbxneri (41.7%). The highest resistance rate was that of tetracycline (88.1%) followed by trimethoprim-sulfamethoxazole (79.3%) and ampicillin (65.5%); 50.8% of isolates were resistant to chloramphenicol, 43.6% to amoxicillin/clavulanic acid, and less than 1% to cefotaxime, ceftazidime, gentamicin, and ciprofloxacin. In S. sonnei, the most common resistance profile corresponded to trimethoprim-sulfamethoxazole (92%) whereas in S. fbxneri the most common antibiotic profiles were multidrug resistance. Conclusions. In Colombia, children under five years are affected by all Shigella species. These findings should guide funders and public health officials to make evidence-based decisions for protection and prevention measures. The antimicrobial resistance characteristics found in this study underline the importance of combating the dissemination of the most frequently isolated species, S. sonnei and S. ftexneri.

Resumen | Introducción. La shigelosis es endémica en los países de ingresos bajos y medios y ocasiona aproximadamente 125 millones de episodios de diarrea y 160.000 muertes al año, un tercio de los cuales se presenta en niños. Objetivo. Describir las características y los perfiles de resistencia antimicrobiana en aislamientos de Shigella spp. recuperados en Colombia entre 1997 y 2018. Materiales y métodos. Los aislamientos provenían de laboratorios en 29 departamentos de Colombia. La serotipificación se hizo con antisueros específicos de Shigella spp. y, la determinación de los perfiles de resistencia y la concentración inhibitoria mínima de diez antibióticos, por Kirby-Bauer. Resultados. Se estudiaron 5.251 aislamientos de Shigella spp. obtenidos de materia fecal (96,4 %); el 47,8 % de ellos correspondía a niños menores de cinco años. Las especies más frecuentes fueron S. sonnei (55,1 %) y S. ftexneri (41,7 %). Se presentó resistencia a tetraciclina (88,1 %), trimetoprim-sulfametoxasol (79,3 %), ampicilina (65,5 %), cloranfenicol (50,8 %) y amoxicilina-acido clavulánico (43,6 %). La resistencia no superó el 1 % contra cefotaxime, ceftazidima, gentamicina y ciprofloxacina. Para S. sonnei, el perfil de resistencia más frecuente correspondió a trimetoprim-sulfametoxasol, en contraste con S. ftexneri, cuyos perfiles fueron todos multirresistentes. Conclusiones. Los niños menores de cinco años se vieron afectados por todas las especies de Shigella spp., aspecto que los legisladores en salud pública deben considerar a la hora de tomar decisiones en torno a las medidas de prevención y protección frente a esta enfermedad. Las características de resistencia antimicrobiana de los aislamientos de Shigella spp. en Colombia ponen de manifiesto la importancia de combatir la diseminación de las dos especies más frecuentes en casos clínicos, S. sonnei y S. ftexneri.

Renal tubular acidosis associated with trimethoprim-sulfamethoxazole poisoning / Acidosis tubular renal asociada a intoxicación por trimetoprim-sulfametoxazol

Abstract The combination of trimethoprim-sulfamethoxazole (TMP-SMZ or cotrimoxazole) has a bactericidal effect on gram-positive cocci and gram-negative bacilli. It is used clinically for skin and soft tissue, respiratory and urinary tract infections, and is also relevant for prophylaxis and treatment of opportunistic infections in immunosuppressed patients. Its use at established doses in immunocompetent patients is safe, with a low rate of adverse events. However, in immunosuppressed individuals (human immunodeficiency virus [HIV], transplants, or steroid users), the adverse effects (AEs) of this medication reach 83%; and, when administered parenterally at high doses, lactic acidosis has been documented secondary to the polyethylene glycol vehicle. We present two cases of patients who ingested an overdose of TMP-SMZ and developed type 2 renal tubular acidosis (RTA), which has not been described with this medication, and whose hyperlactatemia is not explained by the polyethylene glycol excipient, as it was taken orally.

Resumen La combinación de trimetoprim-sulfametoxazol (TMP-SMZ o cotrimoxazol) tiene efecto bactericida sobre cocos gram positivos y bacilos gram negativos, con uso clínico en infecciones de piel y tejidos blandos, del tracto respiratorio y urinario, además con relevancia en la profilaxis y tratamiento de infecciones oportunistas en pacientes inmunosupresos. Su uso en pacientes inmunocompetentes a dosis establecidas es seguro, con una baja tasa de eventos adversos. Sin embargo, en población con inmunosupresión: virus de inmunodeficiencia humana (VIH), trasplante, o usuarios de esteroides; los efectos adversos (EA) por este medicamento alcanzan 83% y por administración parenteral en dosis elevadas se ha documentado acidosis láctica secundaria al vehículo polietilenglicol. Presentamos dos casos de pacientes que ingirieron TMP-SMZ en sobredosis, desarrollando acidosis tubular renal (ATR) tipo 2, la cual no se ha descrito en este medicamento y cuya hiperlactatemia no es explicable por el excipiente polietilenglicol debido a que el consumo fue oral.

Loss of tolerance 5 days after discontinuing sulphonamide introduced via desensitization in delayed reaction / Perda da tolerância 5 dias após suspensão de sulfonamida introduzida através de dessensibilização por reação tardia

ABSTRACT The fixed drug eruption is a non-immediate hypersensitivity reaction to drug, characterized by recurrent erythematous or violaceous, rounded, well-defined border plaques, which always appear in the same location every time the culprit drug is administered. The usual practice is to avoid the drug involved and to use a structurally different drug. However, there are situations in which there is no safe and effective therapy. In such situations, desensitization is the only option. We describe the case of a patient who presented fixed eruption due to sulfamethoxazole-trimethoprim, who underwent successful desensitization, but required a repeat procedure twice due to relapse after inadvertent full-dose reintroduction. In non-immediate hypersensitivity reaction to drug, the indication is controversial and there is no technical standardization. Furthermore, the time at which such tolerance is lost after discontinuing the drug involved is unknown. In severe non-immediate reactions of types II and III, desensitization is contraindicated. The patient underwent desensitisation to sulfamethoxazole-trimethoprim three times − the first with recurrence of lesions and the second and third without manifestations, all concluded successfully and with no premedication.

RESUMO A erupção fixa por drogas é uma reação de hipersensibilidade a medicamento não imediata, caracterizada por placas eritematosas ou violáceas, arredondadas, recorrentes, de bordas bem definidas e que aparecem sempre na mesma localização cada vez que o medicamento culpado é administrado. A prática habitual é evitar a droga envolvida e utilizar um medicamento estruturalmente diferente. Contudo, há situações em que não há terapêutica segura e eficaz. Em tais situações, a dessensibilização é a única opção. Descrevemos o caso de um paciente que apresentou erupção fixa por drogas por sulfametoxazol-trimetoprim, tendo sido submetido à dessensibilização com sucesso, mas necessitou repetição do procedimento duas vezes, por recidiva da reação após reintrodução inadvertida em dose plena. Em reação de hipersensibilidade a medicamento não imediata, a indicação é controversa e não há padronização técnica. Além disso, não se conhece o tempo durante o qual essa tolerância é perdida após a suspensão da droga envolvida. Nas reações não imediatas graves e dos tipos II e III, a dessensibilização está contraindicada. O paciente foi submetido a dessensibilização ao sulfametoxazol-trimetoprim por três vezes − a primeira com recorrência de lesões, e a segunda e terceira sem manifestações, sendo todas concluídas com sucesso e sem uso de pré-medicação.

Hipercalemia inducida por trimetoprim-sulfametoxazol / Hyperkalemia induced by trimethoprim-sulfamethoxazole

Resumen: La hipercalemia inducida por el trimetoprim-sulfametoxazol, descrita en 1983, es un efecto secundario relativamente común pero en ocasiones no diagnosticado que puede poner en peligro la vida de los pacientes. Existen condiciones que aumentan el riesgo de padecerla, entre las que se encuentran, por ejemplo, la diabetes mellitus y la administración de inhibidores del sistema renina-angiotensina. Se describe el caso de una paciente que, al tercer día de administración de trimetoprim-sulfametoxazol para el tratamiento de una infección de vías urinarias recurrente tuvo hipercalemia severa en el contexto del tratamiento conjunto con inhibidores del sistema renina-angiotensina, que remitió con medidas anticalémicas y con la suspensión del tratamiento antibiótico.

Abstract: Hyperkalemia induced by trimethoprim-sulfamethoxazole therapy, described in 1983, is a frequent, yet less thought-off complication that can be dangerous and can cause death. There are conditions that increase the risk of presenting it, including, for example, diabetes mellitus and the use of renin-angiotensin system inhibition. This paper describes the case of a female patient who, on the third day of administration of trimethoprim-sulfamethoxazole for the management of a recurrent urinary tract infection, presented severe hyperkalemia, in the context of concomitant use of renin-angiotensin system inhibition, that was cured with antikalemic measures and with the suspension of antibiotic treatment.

Pulmonary nocardiosis: Report of two cases from a tertiary care hospital

Pulmonary nocardiosis is an uncommon bacterial infection that may lead to severe disease in immunocompromised patients. The disease is rare in immunocompetent patients. Reported cases are few, and the literature is limited because disease recognition is difficult. We present a case report of two patients of pulmonary nocardiosis, who had different clinicoradiological presentations and also responded differently to treatment. Given the rising incidence of cancer, organ transplantation, and use of parenteral steroids, Nocardia is likely to attain a higher place among the causes of pulmonary infections.

Reporte de un caso clínico de Síndrome de Stevens Johnson por uso de Lamotrigina / Report of a clinical case of Stevens Johnson Syndrome due to the use of Lamotrigine

El Síndrome de Stevens-Johnson (SJS) es una urgencia dermatológica rara pero potencialmente fatal que se diferencia de le necrólisis epidérmica tóxica en el porcentaje de desprendimiento de piel y que amerita tratamiento agresivo que incluya retiro de la medicación que provoca el síndrome, manejo de heridas, líquidos de reanimación, uso de inmunoglobulina y soporte nutricional temprano para impactar en el desenlace final. Entre los factores que se han correlacionado con un peor pronóstico se hallan la edad del paciente, alteraciones hematológicas como trombocitopenia, neutropenia y linfopenia, además de la alteración de la función renal. El caso que reportamos es el de un paciente masculino de 6 años con antecedentes de Trastorno del espectro autista y epilepsia manejado con ácido valpróico que ameritó cambio a lamotrigina por no conseguir el medicamento. El paciente desarrolló una faringoamigdalitis que se manejó con trimetoprim-sulfametoxazol y 4 días después de haber finalizado el antibiótico y 12 días después de haber iniciado la lamotrigina desarrolló el SJS; fue manejado en unidad de cuidados intensivos pediátricos con hidratación, uso de inmunoglobulina, antibióticos y curación de heridas con evolución favorable permitiendo egreso luego de 19 días

Stevens-Johnson Syndrome (SJS) is a rare but potentially fatal dermatological emergency that differs from toxic epidermal necrolysis in the percentage of skin detachment and that merits aggressive treatment that includes withdrawal of the medication that causes the syndrome, management of wounds, resuscitation fluids, use of immunoglobulin and early nutritional support to impact the final outcome. Among the factors that have been correlated with a worse prognosis are the patient's age, haematological alterations such as thrombocytopenia, neutropenia and lymphopenia, as well as impaired renal function. The case we report is a 6-year-old male child with a history of Autism Spectrum Disorder and epilepsy managed with valproic acid that warranted a change to lamotrigine for not getting the medication. The patient developed a pharyngotonsillitis that was managed with trimethoprim-sulfamethoxazole and 4 days after the antibiotic was finished and 12 days after starting lamotrigine he developed SJS; he was managed in pediatric intensive care unit with hydration, use of immunoglobulin, antibiotics and wound healing with favorable evolution allowing discharge after 19 days

Effect of trimethoprim-sulfamethoxazole vs. norfloxacin on fecal E. coli resistance pattern and efficacy in patients receiving prophylaxis for spontaneous bacterial peritonitis

Background: Spontaneous Bacterial Peritonitis (SBP) is an infection of ascitic fluid. It is highly mortal and recurrent condition, so prophylaxis with Norfloxacin (NOR) or Trimethoprim-sulfamethoxazole (TMP-SMX) seems to play an important role in the prevention of further episodes of SBP. Aims of the study were to assess the effect of TMP-SMX/NOR on the sensitivity pattern of fecal E. coli after long term prophylaxis in Spontaneous Bacterial Peritonitis (SBP) and to compare the efficacy of TMP-SMX and NOR in prophylaxis of SBP.Methods: An interventional, prospective, open label, single center study conducted in Maulana Azad medical college, New Delhi, India. 52 patients of SBP or with high risk of SBP were screened and finally 39 patients were recruited. Stool sensitivity testing of fecal E. coli was done and they were divided into TMP-SMX group(n=18) and NOR group(n=21) according to sensitivity. After 45±3 days (7 weeks) their stool sample was re-examined for change sensitivity pattern of E. coli. Efficacy variables like any episode of SBP, fever (FEV) resolution of ascites (ASC), bacteremia (BACT), extraperitoneal infection (EPI), liver transplantation (LT) or death (D) were noted throughout the period of 24 weeks.Results: Resistance developed in 60% vs. 48% in TMP-SMX vs. NOR group(p=0.46) after 45 days of prophylaxis. By the end of 24 weeks, Incidence of SBP (29%vs. 25%, p>0.99), episodes of FEV(P=0.60), EPI(p>0.99), ASC(p>0.99) and death (14% vs. 16%, p>0.99) were almost similar in both the groups (TMP-SMX vs. NOR) respectively.Conclusions: Both TMP-SMX and NOR showed same degree of resistance and found equi-efficacious when administered as long-term prophylactic therapy in SBP. TMP-SMX can be a suitable as well as cost effective alternative to NOR for the prophylaxis of SBP.

Sensibilidad a trimetoprima-sulfametoxazol de Streptococcus pyogenes aislados de infecciones invasivas / Susceptibility of Streptococcus pyogenes isolated from invasive infections to trimethoprim-sulfamethoxazole

Se cree erróneamente que los estreptococos del grupo A (EGA) son universalmente resistentes a trimetoprima-sulfametoxazol (TMS). Esto se debe a que la timidina presente en los medios habitualmente usados para determinar sensibilidad in vitro a antibióticos antagoniza el efecto antibiótico de TMS. El objetivo de este trabajo fue determinar la sensibilidad de EGA a TMS, en presencia y ausencia de timidina. A tal fin, fueron analizados 95 aislamientos clínicos obtenidos de tejidos normalmente estériles con infección invasiva por EGA. La pruebas de sensibilidad por difusión con discos de TMS fueron realizadas en agar Mueller Hinton adicionado ya sea con 5% de sangre de carnero (MH-SC) o con 5% de sangre equina lisada (MH-SEL). La sangre equina lisada contiene timidina fosforilasa, que degrada este nucleósido. Como método de referencia se utilizó la epsilometría (Etest). El control de calidad con la cepa Enterococcus faecalis ATCC 29212 fue satisfactorio para ambos medios. La sensibilidad a TMS por difusión fue 100% en MH-SEL; en agar MH-SC 6 (6.3%) aislamientos resultaron resistentes; por Etest todos fueron sensibles, excepto uno de esos seis que presentó sensibilidad intermedia (CIM = 1.5/28.5 μg/ml). En este aislamiento no se encontraron las mutaciones genéticas de EGA más frecuentemente asociadas a resistencia a TMS. Probablemente, si se establecieran mejores puntos de corte para difusión, específicos para EGA, podría optimizarse la correlación con métodos de dilución o con Etest, aun empleando MH-SC.

It is erroneously believed that group A streptococci (GAS) are universally resistant to trimethoprim-sulfamethoxazole (TMS). This is mainly because media commonly used for in vitro determination of susceptibility to antibiotics contain thymidine, a nucleoside that antagonizes the antibiotic effect of TMS. The objective of this work was to determine EGA sensitivity to TMS in the presence and absence of thymidine. To this aim, 95 GAS isolates obtained from clinical tissues with i nvasive infections were analyzed. Susceptibility tests were performed by diffusion with TMS discs in Mueller Hinton agar supplemented either with 5% sheep blood or with 5% lysed equine blood (MH-LEB). Lysed equine blood contains thymidine phosphorylase, which degrades this nucleoside. Epsilometry (Etest) was used as gold standard. Quality controls with Enterococcus faecalis strain ATCC 29212 were satisfactory with both media. A 100% sensitivity to TMS was found in MH-SEL whereas 6 isolates (6.3%) resulted resistant in MH-SC; only one of them was found to have intermediate susceptibility by Etest (MIC > 1.5/28 μg/ml). The genetic determinants most frequently associated to TMS resistant EGA were not found in this isolate. Probably, if more accurate GAS-specific cut-off points were established for diffusion, the correlation with dilution methods or with the Etest could be improved, even employing MH-SB.

El tratamiento de la cistitis aguda no complicada de la mujer en la comunidad ¿es un problema resuelto en el país?

RESUMEN Introducción: la práctica de la Medicina enfrenta frecuentemente al manejo de pacientes del sexo femenino con infección de vías urinarias no complicada, en las que se necesita iniciar un tratamiento empírico para Escherichia coli, basado en la identificación de los llamados antibióticos de primera línea para dicho germen y en el conocimiento de la resistencia local a los mismos. Objetivos: analizar los textos de Medicina Interna, Nefrología, Microbiología, guías internacionales y otras publicaciones recientes para identificar los antibióticos como los de primera línea para el tratamiento de la cistitis aguda no complicada en la mujer: nitrofurantoína, fosfomicina, cotrimoxazol (trimetoprim-sulfametoxazol) y pivmecillinam. Resultados: de los antibióticos mencionados sólo están disponibles en el país la nitrofurantoína y el cotrimoxazol. En un estudio que hemos publicado recientemente se encontró que la resistencia de Escherichia coli a la nitrofurantoína fue 4% y al cotrimoxazol fue del 35%. Conclusión: de los antibióticos considerados de primera línea para el tratamiento empírico de la cistitis aguda no complicada en la mujer, solo tenemos disponible en el país la nitrofurantoína y el cotrimoxazol, siendo baja (4%) la resistencia local de Escherichia coli a la nitrofurantoina y elevada (35%) al cotrimoxazol.

ABSTRACT Introduction: The practice of medicine frequently faces the management of female patients with uncomplicated urinary tract infection, in which an empirical treatment for Escherichia coli is needed, based on the identification of the so-called first-line antibiotics for this germ and in the knowledge of local resistance to them. Objectives: To analyze the texts of Internal Medicine, Nephrology, Microbiology, international guidelines and other recent publications to identify the following antibiotics as those of first line for the treatment of uncomplicated acute cystitis in women: nitrofurantoin, fosfomycin, cotrimoxazole (trimethoprim -sulfamethoxazole) and pivmecillinam. Results: Of the above mentioned antibiotics, only nitrofurantoin and cotrimoxazole are available in Paraguay. In a study we recently published it was found that the resistance of E. coli to nitrofurantoin was 4% and to cotrimoxazole 35%. Conclusion: Of the antibiotics considered as of first line for the empirical treatment of uncomplicated acute cystitis in women, only nitrofurantoin and cotrimoxazole are available in the country, being low (4%) the local resistance of E. coli to nitrofurantoin and high (35%) to cotrimoxazole.