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PURPOSE OF REVIEW: This review comments on the current guidelines for the treatment of wound infections under definition of acute bacterial skin and skin structure infections (ABSSSI). However, wound infections around a catheter, such as driveline infections of a left ventricular assist device (LVAD) are not specifically listed under this definition in any of the existing guidelines. RECENT FINDINGS: Definitions and classification of LVAD infections may vary across countries, and the existing guidelines and recommendations may not be equally interpreted among physicians, making it unclear if these infections can be considered as ABSSSI. Consequently, the use of certain antibiotics that are approved for ABSSSI may be considered as 'off-label' for LVAD infections, leading to rejection of reimbursement applications in some countries, affecting treatment strategies, and hence, patients' outcomes. However, we believe driveline exit site infections related to LVAD can be included within the ABSSSI definition. SUMMARY: We argue that driveline infections meet the criteria for ABSSSI which would enlarge the 'on-label' antibiotic armamentarium for treating these severe infections, thereby improving the patients' quality of life.
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Insuficiencia Cardíaca , Corazón Auxiliar , Infecciones Relacionadas con Prótesis , Enfermedades Cutáneas Infecciosas , Infecciones de los Tejidos Blandos , Infección de Heridas , Humanos , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/complicaciones , Corazón Auxiliar/efectos adversos , Calidad de Vida , Antibacterianos/uso terapéutico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Infección de Heridas/complicaciones , Infección de Heridas/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
PURPOSE: Data on the efficacy, dosing and safety of letermovir for the compassionate therapeutic use of CMV infections are limited. METHODS: Clinical and virological efficacy of letermovir was assessed in a retrospective single-centre study of patients who received letermovir for the compassionate therapeutic use of CMV infections. RESULTS: Letermovir initiation yielded prompt treatment response in 7 out of 9 patients (77.7%). CONCLUSION: Letermovir may be an effective and well tolerated option in the compassionate treatment of CMV infections, although recurrence of CMV and emergence of resistance may be issues.
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Acetatos , Antivirales , Infecciones por Citomegalovirus/tratamiento farmacológico , Quinazolinas , Acetatos/uso terapéutico , Anciano , Antivirales/uso terapéutico , Ensayos de Uso Compasivo , Citomegalovirus/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quinazolinas/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We report of two cases of progressed COVID-19 with negative PCR tests from nasopharyngeal swabs, in whom diagnosis was made by different antibody assays, including a lateral flow rapid test and multiple commercial ELISAs, finally confirmed by comprehensive serological assays. These cases highlight that commercial ELISAs and even rapid tests might significantly aid the diagnosis of COVID-19, particularly, if a combination of serological assays is used with a specific clinical question, in severely ill patients after seroconversion and when comprehensive serological methods are used for confirmation.
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Anticuerpos Antivirales/sangre , COVID-19/diagnóstico , Ensayo de Inmunoadsorción Enzimática/estadística & datos numéricos , SARS-CoV-2/inmunología , Anciano , COVID-19/inmunología , COVID-19/virología , Prueba de COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nasofaringe/virología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2/genética , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: Clearance via renal replacement therapy (RRT) can significantly alter the pharmacokinetic profile of drugs. The aim of this study was (i) to improve the use of clinical trial data and (ii) to provide a model that allows quantification of all aspects of drug elimination via RRT including adsorption to dialysis membranes and/or degradation of the drug in the dialysate. METHODS: An integrated dialysis pharmacometric (IDP) model was developed to simultaneously incorporate all available RRT information. The sensitivity, accuracy and precision of the IDP model was compared to conventional approaches in clinical trial simulations and applied to clinical datasets of teicoplanin and doripenem. RESULTS: The IDP model was more accurate, precise and sensitive than conventional plasma-concentration-based approaches when estimating the clearanceRRT (relative bias <1%). In contrast to conventional approaches, adsorption and degradation were quantifiable using the IDP model (relative bias: -1.1% and - 1.9%, respectively). Applied to clinical data, clearanceRRT, drug degradation (effluent-half-lifedoripenem: 13.5 h-1) and adsorption (polysulphone adsorption capacityteicoplanin: 31.2 mg) were assessed. CONCLUSION: The IDP model allows accurate, precise and sensitive characterization of clearanceRRT, adsorption and degradation. Successful quantification of all aspects of clearanceRRT in clinical data demonstrated the benefit of the IDP model as compared to conventional approaches.
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Lesión Renal Aguda/terapia , Antibacterianos/farmacología , Doripenem/farmacología , Modelos Biológicos , Teicoplanina/farmacocinética , Adsorción , Simulación por Computador , Sistemas de Administración de Bases de Datos , Estabilidad de Medicamentos , Humanos , Tasa de Depuración Metabólica , Estudios Prospectivos , Diálisis Renal/métodos , Terapia de Reemplazo Renal , Medición de RiesgoRESUMEN
The original version of this article unfortunately contained a mistake. The presentation of Fig. 1 was incorrect. The corrected figure is given below.
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The article "Fidaxomicin for the treatment of Clostridium difficile infection (CDI) in at-risk patients with inflammatory bowel disease, fulminant CDI, renal impairment or hepatic impairment: a retrospective study of routine clinical use (ANEMONE)", written by M.J.G.T. Vehreschild et al., was originally published at Springerlink on 11 August 2018 without open access.
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PURPOSE: Dalbavancin is a novel lipoglycopeptide with potent activity against several gram-positive pathogens, an excellent safety profile and a long elimination half-life. METHODS: In this case series observed at the University Hospital of Vienna between 2015 and 2017, all adult patients with gram-positive infections who received at least one dosage of dalbavancin were screened (n = 118). A total of 72 patients were included in the final analysis. The number of included patients stratified by the source of infection was: skin and soft tissue infection (SSTI) (n = 26), osteomyelitis (n = 20), spondylodiscitis (n = 14), acute septic arthritis (n = 4) and prosthetic joint infection (n = 8). RESULTS: In 46 patients (64%), clinical cure was detected at the end of dalbavancin therapy without additional antibiotic therapy. Of the 26 patients who received additional antibiotic therapy other than dalbavancin, 15 patients (21%) showed no clinical improvement under dalbavancin therapy, four patients (5%) had side effects (nausea n = 1, exanthema n = 2, hyperglycemia n = 1), and in seven patients (10%) clinical improvement under dalbavancin therapy was detected but antibiotic therapy was de-escalated to an oral drug. CONCLUSION: We demonstrated high clinical effectiveness of dalbavancin for acute gram-positive infections primarily acute SSTI, acute septic arthritis, acute osteomyelitis and spondylodiscitis. In patients with biofilm-associated infection (chronic infection or joint prosthesis), source control was absolutely necessary for treatment success.
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Antibacterianos/uso terapéutico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Teicoplanina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Austria , Femenino , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Cutáneas Infecciosas/microbiología , Infecciones de los Tejidos Blandos/microbiología , Teicoplanina/uso terapéutico , Adulto JovenRESUMEN
PURPOSE: The aim of this study was to evaluate the pre-operative performance of an automated multiplex PCR (mPCR) system in patients with suspected periprosthetic joint infection (PJI). METHODS: Under sterile conditions, synovial fluid samples from patients with a suspected PJI were collected pre-operatively. One hundred eighty microliter of the aspirate was used for analysis in the mPCR. The remaining joint fluid was sent for microbiological analysis. PJI was diagnosed by using the Musculoskeletal Infection Society (MSIS) criteria. Total percentage agreement and Cohen's kappa coefficient were calculated to measure overall agreement. RESULTS: Overall, 90 patients with a suspected PJI were included. Using MSIS criteria, 38 (42%) patients were classified as septic. Total percent agreement between mPCR and synovial fluid culture was 86% with a Cohen's kappa of 0.68. The mPCR and synovial fluid culture showed sensitivities of 71% and 84%, respectively. Combined evaluation provided an even higher sensitivity of 92%. While Cutibacterium spp. were detected five times by mPCR, it could only be cultured once. A higher detection rate of CoNS by mPCR (n = 7) compared to conventional culture (n = 5) was also demonstrated. In comparison to synovial fluid culture, the mPCR missed Staphylococcus aureus five times. CONCLUSION: With a moderate agreement between synovial fluid mPCR and culture, the mPCR system could be a useful adjunct in diagnosing a PJI pre-operatively. Due to faster availability of results and a higher detection rate of low-virulent microorganisms, it can complement conventional culture.
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Reacción en Cadena de la Polimerasa Multiplex/métodos , Infecciones Relacionadas con Prótesis/microbiología , Líquido Sinovial/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Técnicas Bacteriológicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Infecciones Relacionadas con Prótesis/diagnóstico , Sensibilidad y EspecificidadRESUMEN
The clinical outcomes and safety of dalbavancin as primary and sequential treatment of gram-positive bacteremia with infective endocarditis were evaluated retrospectively. The clinical success rate was high (92.6%), but in 24 of 27 patients dalbavancin was used only after clearance of bacteria from the bloodstream.
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Antibacterianos/uso terapéutico , Endocarditis Bacteriana/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Teicoplanina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Austria , Bacteriemia/tratamiento farmacológico , Femenino , Infecciones por Bacterias Grampositivas/sangre , Hospitales Generales , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Teicoplanina/uso terapéutico , Resultado del TratamientoRESUMEN
Information is limited or lacking on fidaxomicin treatment of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease, fulminant or life-threatening CDI, severe renal impairment, moderate-to-severe hepatic impairment and pregnancy. The ANEMONE study investigated fidaxomicin use in a routine clinical setting, focusing on these medical conditions of specific interest (MCSIs). This retrospective, post-authorisation study reviewed hospital records from Austria, Germany, Spain and the UK (June 2012-June 2015), collecting data from hospital admission to 30 days after last fidaxomicin dose. The primary objective was to identify the proportion of fidaxomicin-treated patients with MCSIs. Secondary objectives were to describe 30-day mortality, changes in ECG and laboratory parameters, fidaxomicin exposure and CDI response (resolution of diarrhoea; 30-day recurrence). 45.3% (261/576) of patients had ≥ 1 MCSI. Thirty-day mortality (post-first dose) was 17.0% (98/576) in the total population and slightly higher (24.6-27.6%) in patients with fulminant CDI or severe renal impairment. 29.6% (24/81) deaths of known cause were attributable to CDI. Of changes in laboratory parameters or ECG findings, only a decrease in leucocyte counts appeared associated with fidaxomicin, consistent with a positive treatment response. Diarrhoea resolved in 78.0% (404/518) of treatment episodes; diarrhoea resolution was lowest in patients with fulminant CDI (investigator-defined, 67.5%, 56/88) and severe renal impairment (68.0%, 68/100). Thirty-day recurrence (18.8%, 79/420) was similar across MCSI subgroups. Although almost half of fidaxomicin-treated patients had ≥ 1 MCSI, the majority of patients in all subgroups had positive responses to treatment, and no particular safety concerns were identified.
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Antibacterianos/efectos adversos , Clostridioides difficile/efectos de los fármacos , Infecciones por Clostridium/microbiología , Fidaxomicina/efectos adversos , Enfermedades Inflamatorias del Intestino/etiología , Hepatopatías/etiología , Insuficiencia Renal/etiología , Adolescente , Adulto , Antibacterianos/uso terapéutico , Niño , Infecciones por Clostridium/complicaciones , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/tratamiento farmacológico , Electrocardiografía , Fidaxomicina/uso terapéutico , Estudios de Seguimiento , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Estimación de Kaplan-Meier , Hepatopatías/diagnóstico , Persona de Mediana Edad , Insuficiencia Renal/diagnóstico , Estudios Retrospectivos , Adulto JovenAsunto(s)
Mpox , Humanos , Mpox/diagnóstico , Mpox/epidemiología , Progresión de la Enfermedad , Brotes de EnfermedadesAsunto(s)
Borrelia burgdorferi , Borrelia , Enfermedad de Lyme , Administración Cutánea , Biopelículas , Humanos , Enfermedad de Lyme/diagnóstico , PielRESUMEN
BACKGROUND AND CASE PRESENTATION: We report a case of septic shock syndrome caused by Streptococcus pneumoniae in a patient who had undergone splenectomy due to an autoimmune lymphoproliferative syndrome (ALPS), which is characterized as a dysfunction of immunoregulation. Although the patient was vaccinated with a conjugated polysaccharide vaccine after the splenectomy, he was still susceptible to S. pneumoniae infection, because the isolated serovar (24F), a serovar long thought to be apathogenic, is not covered by any vaccine currently approved, neither a conjugated nor an unconjugated polysaccharide one. CONCLUSIONS: This case demonstrates that, due to presence of different serovars, also infections with bacteria against which patients are vaccinated have to be considered as differential diagnosis. Although vaccine development has extended the coverage of S. pneumoniae from 7 to 23 serovars within recent years, there is still demand for novel vaccines which can provide broader protection also against so-thought "apathogenic" strains, especially for groups at high risk.
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Infecciones Neumocócicas/complicaciones , Vacunas Neumococicas/farmacología , Choque Séptico/microbiología , Adulto , Síndrome Linfoproliferativo Autoinmune/cirugía , Humanos , Huésped Inmunocomprometido , Masculino , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/prevención & control , Serogrupo , Choque Séptico/tratamiento farmacológico , Esplenectomía , Streptococcus pneumoniae/inmunología , Streptococcus pneumoniae/aislamiento & purificación , Streptococcus pneumoniae/patogenicidad , Insuficiencia del Tratamiento , Vacunas Conjugadas/farmacologíaRESUMEN
OBJECTIVE: The antimicrobial agent flucloxacillin is a potential cause of drug-induced liver disease, but the underlying mechanisms for toxicity have not been fully elucidated. As in-vitro and in-vivo findings suggest that biotransformation products contribute to hepatotoxicity, the purpose of this study was to characterize formation and accumulation of its metabolites in patients with renal failure. METHODS: Twelve intensive care patients undergoing continuous venovenous hemofiltration received 4.0 g flucloxacillin as single and repeated infusion. Blood and dialysate samples were collected and analyzed for flucloxacillin and its metabolites by HPLC. RESULTS: The overall amounts of the flucloxacillin metabolites 5'-hydroxymethylflucloxacillin (5-OH-FX), 5'-hydroxymethylflucloxacillin-penicilloic acid (5-OH-PA), and flucloxacillin-penicilloic acid (FX-PA) produced varied considerably between patients, and accounted for 3.62 - 35.9% of total flucloxacillin concentration (flucloxacillin + metabolites) in the plasma. Clearance rates and sieving coefficients for 5-OH-FX and FX-PA were comparable to that of the parent drug, although removal of 5-OH-PA was decreased. Using an isolated perfused rat liver model we demonstrated that 5-OH-FX reached concentrations in the bile (240.5 ± 84.2 nmoles/mL) that were sufficient to exert cytotoxic effects, unlike either of the two penicilloic acids. CONCLUSIONS: Based on data from perfused rat livers, high biliary concentrations of 5-OH-FX might also be observed in our patients explaining why LDH, bilirubin, and alkaline phosphatase were elevated in up to 8/12 patients after repeated infusion of flucloxacillin. Liver toxicity of flucloxacillin might therefore be observed in patients with renal impairment after continuously elevated 5-OH-FX levels.â©.
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Floxacilina/metabolismo , Floxacilina/farmacocinética , Hígado/efectos de los fármacos , Insuficiencia Renal/metabolismo , Anciano , Animales , Biotransformación/efectos de los fármacos , Femenino , Floxacilina/efectos adversos , Semivida , Humanos , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Persona de Mediana Edad , Ácido Penicilánico/efectos adversos , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/metabolismo , Ratas , Diálisis Renal/métodosRESUMEN
Dosage recommendations for cidofovir are available for renally competent as well as impaired patients; however, there are no data for patients undergoing continuous renal replacement therapy. We determined the single-dose concentration-versus-time profile of cidofovir in a critically ill patient undergoing continuous venovenous hemofiltration (CVVH). One dose of 450 mg cidofovir (5 mg/kg) was administered intravenously due to a proven cytomegalovirus (CMV) infection and failure of first-line antiviral therapy. Additionally, 2 g of probenecid was administered orally 3 h prior to and 1 g was administered 2 h as well as 8 h after completion of the infusion. The concentrations of cidofovir in serum and ultrafiltrate were assessed by high-performance liquid chromatography. The peak serum concentration measured at 60 min postinfusion was 28.01 mg/liter at the arterial port. The trough serum level was 19.33 mg/liter at the arterial port after 24 h. The value of the area under the concentration-versus-time curve from 0 to 24 h was 543.8 mg·h/liter. The total body clearance was 2.46 ml/h/kg, and the elimination half-life time was 53.32 h. The sieving coefficient was 0.138±0.022. Total removal of the drug was 30.99% after 24 h. Because of these data, which give us a rough idea of the concentration profile of cidofovir in patients undergoing CVVH, a toxic accumulation of the drug following repeated doses may be expected. Further trials have to be done to determine the right dosage of cidofovir in patients undergoing CVVH to avoid toxic accumulation of the drug.
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Antivirales/farmacocinética , Citosina/análogos & derivados , Hemofiltración , Organofosfonatos/farmacocinética , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Cidofovir , Enfermedad Crítica , Citosina/administración & dosificación , Citosina/farmacocinética , Citosina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Organofosfonatos/administración & dosificación , Organofosfonatos/uso terapéutico , Probenecid/uso terapéuticoRESUMEN
Ganciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.
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Antivirales/sangre , Antivirales/farmacocinética , Enfermedad Crítica , Ganciclovir/sangre , Ganciclovir/farmacocinética , Hemodiafiltración , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método de MontecarloAsunto(s)
Enfermedad de Bowen/virología , Carcinoma de Células Escamosas/virología , ADN Viral/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Neoplasias Cutáneas/virología , Biomarcadores de Tumor/análisis , Biopsia , Enfermedad de Bowen/química , Enfermedad de Bowen/patología , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patología , Genotipo , Mano , Pruebas de ADN del Papillomavirus Humano , Humanos , Inmunohistoquímica , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/transmisión , Neoplasias Cutáneas/química , Neoplasias Cutáneas/patologíaRESUMEN
Leveraging the capabilities of a microbiological clinical analytics tool, this study delves into quantifying the public health impact of antibiotic-resistant bacteria. Focusing on eight predominant antibiotic-resistant bacteria, the study utilizes University Hospital Vienna's data to calculate the burden of antibiotic-resistant infections in disability-adjusted life years. The results highlight the potential of extended analytics tools in epidemiological research and underscore the pressing challenge of antimicrobial drug resistance.
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Infecciones Bacterianas , Humanos , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Farmacorresistencia Bacteriana , Austria , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Años de Vida Ajustados por Calidad de VidaRESUMEN
Invasive systemic fungal infections are a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation. We report the case of a fatal infection with Hormographiella aspergillata in a patient undergoing allogenic peripheral blood stem cell transplantation for acute myeloid leukaemia.