Drawbacks of the use of cotrimoxazole in foreign-body infections.

INTRODUCTION: The anti-staphylococcal efficacy of cotrimoxazole in the setting of difficult-to-treat infections seems to be compromised by large amounts of pus and devitalized tissue, and, therefore, high levels of thymidine. Our objective was to evaluate the activity of cotrimoxazole against a staphylococcal foreign-body infection experimental model, which also yields significant quantities of thymidine. MATERIAL AND METHODS: We used a rat tissue-cage model of infection (with high inherent thymidine levels) caused by a strain of methicillin-susceptible Staphylococcus aureus (MSSA; ATCC 29213). MIC values were determined (microdilution method) and compared in the presence or absence of tissue-cage fluid samples. RESULTS: The inefficacy of cotrimoxazole was found to be similar to that of the control group. The MIC of cotrimoxazole was 4-8 fold higher in the presence of rat tissue-cage fluid. CONCLUSIONS: The inefficacy of cotrimoxazole in our foreign-body infection model by MSSA, and the probable negative impact of the presence of thymidine on its efficacy, challenge the use of this drug in acute phases of foreign-body infections. It should be reserved as an alternative treatment when the infection is more controlled.

Características clínicas y microbiológicas de las infecciones de piel y tejidos blandos por Staphylococcus aureus en niños de un hospital en Medellín durante los años 2013 a 2015 / Clinical and microbiological characteristics of skin and soft tissue infections caused by Staphylococcus aureus in children in a hospital in Medellin from 2013 to 2015

Resumen Introducción: El principal microorganismo implicado en las infecciones de piel y tejidos blandos (IPTB) es Staphylococcus aureus, con incremento en las cepas resistentes a meticilina en los últimos años. Objetivo: Identificar la frecuencia de S. aureus resistente a meticilina (SARM) en IPTB en niños que consultaron a un hospital de cuarto nivel en la ciudad de Medellín. Métodos: Estudio descriptivo, retrospectivo, a partir de la revisión de historias clínicas. Se incluyeron pacientes menores de 18 años con IPTB causadas por S. aureus que no cumplieran con criterios de enfermedad invasora. Resultados: La prevalencia de SARM en esta población fue de 31%. El principal diagnóstico fue absceso cutáneo (68%), seguido por infección de sitio quirúrgico (15%) y celulitis no purulenta (6%). Tenían alguna co-morbilidad 85% de los pacientes. Todos los aislados fueron sensibles a rifampicina y cotrimoxazol. Ocho por ciento de los aislados fueron resistentes a clindamicina. Se encontró mayor prevalencia de SARM en lactantes comparado con los mayores de 2 años (60 vs 23%, p = 0,0109). Conclusión: Ante la alta prevalencia de SARM en IPTB se recomienda incluir en el tratamiento empírico antimicrobianos con cobertura para estas cepas, principalmente para lactantes.

Background: Skin and soft tissue infections (SSTI) are very common in children and Staphylococcus aureus is the main agent, with an increase of methicillin resistant strains (MRSA) in recent years. Aim: To identify the frequency of MRSA in skin and soft tissue infections (SSTI) in children from a high complex hospital in Medellin, Colombia. Methods: This is a descriptive, retrospective study, information was obtained from medical records. We included patients younger than 18 years with SSTI due to S. aureus who did not meet criteria for invasive disease. Results: The prevalence of MRSA in this population was 31%. The main diagnosis was cutaneous abscess (68%), followed by surgical site infection (15%) and non-purulent cellulitis (6%). Eighty five percent of the patients had at least 1 comorbidity. All isolates were sensitive to rifampicin and cotrimoxazole and 8% of the isolates were resistant to clindamycin. There was a higher prevalence of MRSA in patients under 2 years compared to older (60 vs 23%, p = 0,0109). Conclusion: In view of the high prevalence of MRSA in SSTI, empirical treatment with adequate coverage for MRSA is recommended, especially for patients under 2 years of age.

Effect of cotrimoxazole prophylaxis on malaria occurrence among HIV-infected adults in West Africa: the MALHIV Study.

INTRODUCTION: Cotrimoxazole (CTX) should be given to all HIV-infected adults with mild or severe HIV-disease or those with CD4 counts below 350/mm3 according to 2006 WHO guidelines. We assessed the impact of CTX prophylaxis on the risk of malaria episodes in HIV-1-infected adults from four West African countries with different patterns of malaria transmission. METHOD: Multicentric cohort study, conducted between September 2007 and March 2010 in four West African cities. Antiretroviral therapy (ART) naïve HIV-infected adults started CTX at enrolment (CTX group) if they had CD4 < 350 cells/mm3 or were at WHO clinical stage ≥2. For patients who did not start CTX at enrolment (non-CTX group) and started CTX afterwards, follow-up was censored at CTX initiation. We used Cox's proportional hazard model to compare the risk of malaria between CTX groups. RESULTS: A total of 514 participants (median CD4 count 238 cells/mm3 ) were followed for a median of 15 months. At enrolment, 347 started CTX, and 261 started ART. During the follow-up, 28 started CTX. The incidence of malaria was 8.7/100 PY (95%CI 6.3-11.5) overall, 5.2/100 PY (95%CI 3.1-8.3) in the CTX group and 15.5/100 PY (95%CI 10.3-22.1) in the non-CTX group. In multivariate analysis, CTX led to a 69% reduction in the risk of malaria (aHR 0.31, 95%CI 0.10-0.90). CONCLUSION: Patients in the CTX group had an adjusted risk of malaria three times lower than those in the non-CTX group. The prolonged large-scale use of CTX did not blunt the efficacy of CTX to prevent malaria in this region.

Necrólisis tóxica epidérmica inducida por cotrimoxazol / Epidermic toxic necrolysis induced by co-trimoxazole

Se describe el caso clínico de una paciente de 60 años de edad con antecedentes de hipertensión arterial, por lo cual llevaba tratamiento con nifedipino, quien asistió al Cuerpo de Guardia del Hospital General Docente Orlando Pantoja Tamayo en el municipio de Contramaestre, Santiago de Cuba, por presentar deposiciones diarreicas, vómitos, hipertermia (38 0C) y lesiones generalizadas en la piel en forma de pústulas eritemato-costrosas con flictenas y dolor. La paciente refirió que solía automedicarse con cotrimoxazol por la reiteración de infecciones urinarias y que desde hacía 3 días estaba consumiendo dicho medicamento. El estudio histopatológico mostró una necrólisis tóxica epidérmica (síndrome de Lyell). A pesar de los cuidados médicos, evolucionó desfavorablemente y se complicó con una insuficiencia renal aguda, lo que le condujo a la muerte(AU)

The case report of a 60 years patient with a history of hypertension, reason why she had treatment with nifedipine, who went to the Emergency Room of Orlando Pantoja Tamayo Teaching General Hospital in Contramaestre, Santiago de Cuba, due to diarrheical stools, vomits, hyperthermia (38 0C) and generalized skin injuries in the type of erythemato-scabby pustules with flictenas and pain is described. The patient referred that she was accustomed to self-medication with co-trimoxazole due to repeated urinary infections and that she was consuming this medication for 3 days. The pathological study showed an epidermic toxic necrolysis (Lyell syndrome). In spite of the medical cares, she had an unfavorable clinical course and she complicated with an acute renal failure, leading to death(AU)

Necrólisis tóxica epidérmica inducida por cotrimoxazol / Epidermic toxic necrolysis induced by co-trimoxazole

Se describe el caso clínico de una paciente de 60 años de edad con antecedentes de hipertensión arterial, por lo cual llevaba tratamiento con nifedipino, quien asistió al Cuerpo de Guardia del Hospital General Docente "Orlando Pantoja Tamayo" en el municipio de Contramaestre, Santiago de Cuba, por presentar deposiciones diarreicas, vómitos, hipertermia (38 0C) y lesiones generalizadas en la piel en forma de pústulas eritemato-costrosas con flictenas y dolor. La paciente refirió que solía automedicarse con cotrimoxazol por la reiteración de infecciones urinarias y que desde hacía 3 días estaba consumiendo dicho medicamento. El estudio histopatológico mostró una necrólisis tóxica epidérmica (síndrome de Lyell). A pesar de los cuidados médicos, evolucionó desfavorablemente y se complicó con una insuficiencia renal aguda, lo que le condujo a la muerte

The case report of a 60 years patient with a history of hypertension, reason why she had treatment with nifedipine, who went to the Emergency Room of "Orlando Pantoja Tamayo" Teaching General Hospital in Contramaestre, Santiago de Cuba, due to diarrheical stools, vomits, hyperthermia (38 0C) and generalized skin injuries in the type of erythemato-scabby pustules with flictenas and pain is described. The patient referred that she was accustomed to self-medication with co-trimoxazole due to repeated urinary infections and that she was consuming this medication for 3 days. The pathological study showed an epidermic toxic necrolysis (Lyell syndrome). In spite of the medical cares, she had an unfavorable clinical course and she complicated with an acute renal failure, leading to death

Cotrimoxazol en infecciones óseas: toxicidad e impacto clínico y económico / Cotrimoxazole in bone-related infections: toxicity and clinical and economic impact

Background: Cotrimoxazole is a therapeutic option for bone-related infections but is associated to hyperkalemia and renal failure. Tolerance to this drug may reduce length of stay (LOS) and hospital charges. Aims: To evaluate renal, potassium toxicity, clinical outcome, and use of hospital resources in patients treated with cotrimoxazole for bone-related infections. Methods: Retrospective analysis of adult patients with bone-related infections confirmed by culture and treated with this drug. Serum potassium and creatinine levels were analyzed during follow-up and risk factors for hyperkalemia were searched. Length of stay (LOS) and hospital charges were compared. Clinical outcome was evaluated as a secondary endpoint. Results: From 2011 to 2014, 23 patients were identified (mean age 64.7 years). Diabetes mellitus, peripheral vascular disease, and previous amputations prevalence were high (82.6%, 47.8%, and 43.5%, respectively). Median serum potassium concentration increased significantly at first control (4.35 mEq/L to 4.9 mEq/L; p < 0.001), and also creatinine serum concentration (0.9 to 1.1 mg/dL; p < 0.05). Seven patients developed hyperkalemia. Cotrimoxazole was discontinued in 10 patients (43.5%), and in 6, discharge was postponed. Drugs active against the renin-angiotensin system (DAARAS) were associated with kyperkalemia (OR 10.8 IC95 1.37-85; p < 0.05). LOS was higher among patients with cotrimoxazole toxicity (median LOS 56 versus 30 days, p < 0.05). Patients with no cotrimoxazole interruption had less drug-related hospital charges (median values of 563 versus 2820 USD, respectively; p < 0.01). Conclusions: Cotrimoxazole use must be monitored in order to detect hyperkalemia or renal toxicity and suspend its prescription. Patients that use DAARAS have a higher risk of kyperkalemia. LOS and drug-related hospital charges are reduced when patients can tolerate cotrimoxazole.

Antecedentes: Cotrimoxazol es una alternativa en infecciones óseas pero se ha asociado al desarrollo de falla renal e hiperkalemia. Objetivo: Evaluar toxicidad renal, hiperkalemia, estadía y gastos hospitalarios y evolución clínica en un grupo de pacientes con infecciones óseas tratados con este compuesto. Pacientes y Métodos: Estudio retrospectivo-descriptivo de pacientes adultos con infecciones óseas confirmadas con cultivos y tratados con este compuesto. Seguimiento de creatinina y kalemia y búsqueda de factores de riesgo para hiperkalemia, comparación de gastos y estadía hospitalaria y análisis de eficacia clínica. Resultados: Desde el año 2011 al 2014 se identificaron 23 pacientes (promedio de edad 64,7 años). La prevalencia de diabetes mellitus tipo 2 (82,6%), enfermedad vascular periférica (47,8%) y amputaciones previas (43,5%) fue elevada. La mediana de la kalemia basal aumentó significativamente al primer control (4,35 a 4,9 mEq/L) al igual que la creatinina plasmática (0,9 a 1,1 mg/dL). Siete pacientes desarrollaron hiperkalemia (30,4%). Se suspendió cotrimoxazol en 10 casos (43,5%) y en 6 casos se postergó el alta. El uso de fármacos activos contra el sistema renina-angiotensina (FASRA) se asoció a hiperkalemia (OR 10,8 IC95 1,37-85; p < 0,05). La estadía hospitalaria fue mayor en el grupo con toxicidad a cotrimoxazol (mediana de 56 versus 30 días; p < 0,05) y los pacientes sin suspensión de terapia tuvieron menos gastos por fármacos (medianas de 563 vs 2.820 USD, p < 0,01). Conclusiones: El uso de cotrimoxazol debe ser monitorizado para detectar hiperkalemia o toxicidad renal y suspender su prescripción. Los pacientes que usan FASRA tienen mayor riesgo de hiperkalemia. La estadía y gastos hospitalarios por fármacos son menores en pacientes que toleran el cotrimoxazol.

Effect of cotrimoxazole prophylaxis on malaria occurrence in HIV-infected patients on antiretroviral therapy in sub-Saharan Africa.

OBJECTIVE: To systematically review the evidence on the effect of cotrimoxazole (CTX) on malaria in HIV-positive individuals on antiretroviral therapy (ART). METHODS: Web of Science, PubMed and MEDLINE, EMBASE, Global Health and Cochrane Library databases were searched using terms for malaria, HIV and CTX. Studies meeting the inclusion criteria were reviewed and assessed for bias and confounding. RESULTS: Six studies (in Uganda, Kenya, Malawi, Zambia and Zimbabwe) had relevant data on the effect of CTX on malaria in patients on ART: four were observational cohort studies (OCS) and two were randomised controlled trials (RCTs); two were in children and one in women only. Samples sizes ranged from 265 to 2200 patients. Four studies compared patients on ART and CTX with patients on ART alone; 2 (RCTs) found a significant increase in smear-positive malaria on ART alone: (IRR 32.5 CI = 8.6-275.0 and HR 2.2 CI = 1.5-3.3) and 2 (OCS) reported fewer parasitaemia episodes on CTX and ART (OR 0.85 CI = 0.65-1.11 and 3.6% vs. 2.4% of samples P = 0.14). One OCS found a 76% (95% CI = 63-84%) vs. 83% (95% CI = 74-89%) reduction in malaria incidence in children on CTX and ART vs. on CTX only, when both were compared with HIV-negative children. The other reported a 64% reduction in malaria incidence after adding ART to CTX (RR = 0.36, 95% CI = 0.18-0.74). The 2 RCTs were unblinded. Only one study reported adherence to CTX and ART, and only two controlled for baseline CD4 count. CONCLUSION: Few studies have investigated the effect of CTX on malaria in patients on ART. Their findings suggest that CTX is protective against malaria even among patients on ART.

Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis.

OBJECTIVES: Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. METHODS: We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. RESULTS: Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. CONCLUSIONS: Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children.

Skin infections caused by community-acquired methicillin-resistant Staphylococcus aureus: clinical and microbiological characteristics of 11 cases.

INTRODUCTION: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen that causes skin and soft-tissue infections. OBJECTIVE: To describe the clinical characteristics of skin infections caused by CA-MRSA and correlations with the available demographic and microbiological data. MATERIAL AND METHODS: This was a descriptive study of patients with a microbiologically confirmed diagnosis of CA-MRSA infection treated in a dermatology department between June 2009 and December 2011. We recorded demographic details, the clinical characteristics of lesions, and the treatments used. RESULTS: We studied 11 patients (5 men and 6 women); 91% were under 40 years of age and had no relevant past medical history. The most common presentation was a skin abscess (with or without cellulitis). In all such cases, marked tissue necrosis and little or no purulent exudate was observed when the abscess was drained. Fifty percent of these abscesses had been treated previously with ß-lactam antibiotics, and in all cases the lesions resolved after surgical drainage, which was combined in 63% of cases with quinolones or cotrimoxazole. CONCLUSIONS: Today, skin infections due to CA-MRSA affect healthy young athletes who have no contact with healthcare settings. The most common presentation is a skin abscess characterized by marked tissue necrosis and little or no purulent exudate. In cases with these characteristics in susceptible patients, the involvement of CA-MRSA as the causative agent should be suspected. The abscesses should be drained whenever possible and, if necessary, antibiotic treatment should be prescribed; empirical use of ß-lactam antibiotics should be avoided.

Falla de la profilaxis con cotrimoxazol para la neumonía por Pneumocystis jiroveci con el uso concomitante de leucovorina: Reporte de un caso / Failure of cotrimoxazole prophylaxis for Pneumocystis jiroveci pneumonia with concomitant use of leucovorin: Case report

The concomitant use of leucovorin and cotrimoxazole in PCP can lead to therapeutic failure and increased risk of death due to antagonism. It is important to keep this possible antagonistic interaction in mind even during prophylaxis. This paper presents a case with this failure outcome.

Profilaxis de neumonía por Pneumocystis jiroveci en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against Pneumocystis pneumonia in pediatric and adult patients undergoing solid organ or hematopoietic stem cells transplantation

Pneumocystis jiroveci is an important pathogen in patients undergoing SOT and HSCT. Universal prophylaxis is recommended for all adults and children with SOT and HSCT, considering that its use significantly reduces the occurrence and mortality associated with pneumonia by this agent. The drug of choice is cotrimoxazole (A1) three times a week, low-dose scheme, that has proved equally effective and better tolerated than the daily regimen and/or at high doses. Prophylaxis starts 7 to 14 days post transplant in SOT recipients and post-implant in HSCT, with an average duration of 6 months except in liver and lung transplant as in HSCT with significant degree of immunosuppression, that lasts for 1 year. Alternatives for prophylaxis are dapsone (B2), aerosolized pentamidine (B2) and atovaquone (C2).

Pneumocystis jiroveci es un patógeno importante en pacientes sometidos a TOS y TPH. Se recomienda proilaxis universal a todos los pacientes adultos y niños sometidos a TOS o TPH porque su uso reduce signiicati-vamente la ocurrencia y mortalidad asociada a neumonía por este agente. El medicamento de elección es cotrimoxa-zol (A1) tres veces por semana, en dosis bajas, esquema que ha demostrado igual eicacia y mejor tolerancia que el esquema diario y/o con dosis altas. La proilaxis se inicia 7 a 14 días post trasplante en TOS y posterior al implante en TPH, con una duración promedio de 6 meses salvo en trasplante de hígado y pulmón en que se prolonga por 1 año, al igual que en TPH con grado importante de inmunosupresión. Son alternativas de profilaxis dapsona (B2), pentamidina aerosolizada (B2) y atavacuona (C2).

Difusión de cotrimoxazol a través de un expansor tisular: Estudio in vitro / Cotrimoxazole diffusion through a tissue expanders: In vitro study

Introducción: La principal complicación del uso de los expansores titulares (ET) son las infecciones. Una alternativa para evitarla, es agregar antibióticos que se difundan a través de la pared de un ET y eviten la colonización bacteriana. El objetivo de este trabajo fue evaluar la eficacia de una presentación nacional de cotrimoxazol, para difundirse a través de un ET en diferentes volúmenes de expansión. Material y método: Se realizó un experimento longitudinal con 12 ET, llenados a 50,100, 150 o 200% de su capacidad nominal, con solución fisiológica y cotrimoxazol a una concentración de 800/4000 ug/mL de trimetoprin/sulfametoxazol (TMX/SMX), sumergidos posteriormente en un sistema cerrado. Se midió la presión en el interior del ET, al inicio y al final del experimento. En los cuatro grupos se cuantificó la concentración de cotrimoxazol en la solución del contenedor, durante nueve días consecutivos. Los resultados se compararon mediante ANOVA de dos vías. Resultados: El SMX se precipitó dentro del ET. Las concentraciones de TMX en la solución del contenedor fueron diferentes en función del tiempo y el porcentaje de expansión. No hubo correlación entre el porcentaje de expansión y la presión dentro del ET. Conclusiones: La sinergia de cotrimoxazol de uso endovenoso disponible en nuestro país, no es una buena opción a emplearse en un ET a las dosis utilizadas, ya que el coeficiente de solubilidad de SMX se saturó y se formaron cristales. El incremento de difusión de TMX estuvo asociado con un mayor porcentaje de expansión, lo que es una ventaja, considerando que las infecciones son más frecuentes al final del proceso de expansión.

Introduction: Infection associated with tissue expansion is one of the main complications and force to take away the tissue expander. An alternative to avoid this action is to dilute antibiotics inside it. The aim of this experiment was to quantify the concentration of cotrimoxazole diffused through a tissue expander at different expansion and pressure volumes. Material and methods: A test was performed with 12 tissue expanders immersed in a closed system. These were divided in 4 sets according to the introduced expansion rate. Three independent variables were considered: percentage of lumen volume introduced into the expander, pressure inside the expander, and experiment duration. The concentration of the drug diffused through the expander was taken as dependent variable. The solution in which the expander was immersed was continuously sampled and drug concentration was determined by High Performance Liquid Chromatography (HPLC). ANOVA was used to determine differences between concentrations measured of every variable applied. Results: Only trimethoprim (TMX) diffused. No lineal correlation was observed between expansion rate and pressure inside the expander. The difference with respect to time and concentration of the drug outside the expander was statistically significant among the 4 sets of expanders (p = 0.0000). Conclusion: Sulfametoxazole (SMX) did not diffuse and crystallized inside the expander because of the different pk of the two drugs (SMX-TMX) respect to pH of dilution which was similar to pK of trimethoprim. The expansion rate had a proportional effect on TMX concentration outside the expander: an over-expansion of the system greater than 200% increases diffusion highly.