RESUMEN
INTRODUCTION: Tigecycline has a broad spectrum of activity, including activity against drug-resistant Gram-positive and -negative microorganisms. Its side effects are significant, but hypoglycemia is a rare finding during treatment. We aim to present an event of severe hypoglycemia in a patient with type 2 diabetes mellitus with replacement renal therapy, and hemodialysis after initiating tigecycline. CASE PRESENTATION: A 54-year-old female diagnosed with type 2 diabetes mellitus was under treatment with basal-bolus insulin therapy and oral antihypertensive drugs. She started hemodialysis 24 months ago. She complained of recurrent fever for the last seven months and was treated with several antibiotics. In two separate blood cultures, she tested positive for methicillin-resistant Staphylococcus epidermidis (MRSE). Based on the antibiogram, we started treatment with tigecycline 100 mg/day. After 6-8 hours from the first dose, the patient is complicated with events of hypoglycemia and then continues with severe hypoglycemia (40-47 mg/dL). The patient continued to have hypoglycemia for about 16-18 hours after the last dose. We didn't find any reasons to explain the cause of episodes of hypoglycemia. She did not have high blood insulin levels (insulin 4.11 mIU/L [range 2.6-24.9]). We followed her for six months and the patient did not experience episodes of hypoglycemia. CONCLUSIONS: The association of severe hypoglycemia with tigecycline treatment is a very rare event and published papers on this topic are limited. Clinicians should be aware of this rare event when administering tigecycline and should routinely check blood glucose level during the treatment.
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Antibacterianos , Diabetes Mellitus Tipo 2 , Hipoglucemia , Minociclina , Diálisis Renal , Staphylococcus epidermidis , Tigeciclina , Humanos , Tigeciclina/efectos adversos , Tigeciclina/uso terapéutico , Femenino , Persona de Mediana Edad , Hipoglucemia/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Minociclina/análogos & derivados , Minociclina/efectos adversos , Minociclina/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
OBJECTIVES: This study conducted a network meta-analysis comparing linezolid, teicoplanin, daptomycin, tigecycline, and ceftaroline fosamil with vancomycin for treating MRSA-related diseases, addressing the lack of comprehensive evaluations in existing research on antibiotic therapy for MRSA infections. METHODS: We systematically searched databases including PubMed, Embase, Web of Science, the Cochrane Librar up to August 22, 2023. All eligible randomized controlled trials of the six antibiotics were included in the NMA, and their effectiveness and safety were compared across various MRSA-related diseases. Categorical data were used for the odds ratio (OR), and continuous data were used for mean difference (SMD). The surface under the cumulative ranking (SUCRA) was employed to evaluate the incidence rate. RESULTS: According to SUCRA results, daptomycin was the most effective treatment (73.0%) in bloodstream infections. In pulmonary infections and skin and soft tissue infections, linezolid out-performed other antibiotics in effectiveness rate (90.6% and 86.3%), microbial killing rate (93.3% and 93.1%). Vancomycin showed lower adverse reactions than teicoplanin, with less hepatotoxicity compared to linezolid and tigecycline. Linezolid had higher thrombocytopenia risk but lower nephrotoxicity risk than others. Vancomycin was less effective in microbial killing rates than linezolid across various infections. CONCLUSION: The present research suggests that in pulmonary infections and skin and soft tissue infections, linezolid may be a better option for treating MRSA-related diseases. However, caution is warranted due to the association of linezolid with thrombocytopenia. TRIAL REGISTRATION: Our study protocol was registered with the International Prospective Register of SystematicReviews (PROSPERO); Registration number: CRD42024535142.
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Antibacterianos , Linezolid , Staphylococcus aureus Resistente a Meticilina , Metaanálisis en Red , Infecciones Estafilocócicas , Tigeciclina , Vancomicina , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Vancomicina/uso terapéutico , Vancomicina/efectos adversos , Linezolid/uso terapéutico , Linezolid/efectos adversos , Tigeciclina/uso terapéutico , Tigeciclina/efectos adversos , Teicoplanina/análogos & derivados , Teicoplanina/uso terapéutico , Teicoplanina/efectos adversos , Daptomicina/uso terapéutico , Daptomicina/efectos adversos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/microbiologíaRESUMEN
Tigecycline is a parenteral glycycline antibiotic that is used to treat severe infections caused by susceptible organisms, butitis also associated with hepatotoxicity. We present 2 similar patients with hepatic steatosis possibly associated with early tigecycline after transplant. In the first case, a 61-year-old woman underwent liver transplant for acute severe hepatitis; 6 days posttransplant, because of nonroutine resistant fever, the patient received tigecycline combined with daptomycin. Retransplant was applied to the patient on day 12 posttransplant because of acute liver failure secondary to hepatic vein thrombosis. After retransplant, biochemical levels gradually increased, exceeding the upper limit of normal. In liver biopsy, the patient had macrovesicular steatosis in 70% to 80% ofthe parenchyma. In the second case, a 53-yearold woman underwent liver transplant for liver cirrhosis. Tigecycline was added to the treatment because of recurrent fever on day 6 after transplant, with treatment also comprising piperacillin-tazobactam and meropenem. On day 15 of the patient's tigecycline treatment, her liver function tests were elevated. In liver biopsy, the patient had 30% to 40% macrovesicular steatosis and canalicular cholestasis in the parenchyma, especially in zone 3. Reports of hepatic steatosis associated with early tigecycline after transplant are quite new to the literature.
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Antibacterianos , Hígado Graso , Trasplante de Hígado , Tigeciclina , Humanos , Tigeciclina/efectos adversos , Femenino , Persona de Mediana Edad , Trasplante de Hígado/efectos adversos , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Hígado Graso/inducido químicamente , Hígado Graso/diagnóstico , Resultado del Tratamiento , Biopsia , Minociclina/efectos adversosRESUMEN
High-dose tigecycline is gradually being introduced for the treatment of serious infectious diseases due to the increasing difficulty in treating pan-resistant bacterial infections. However, the safety of high-dose tigecycline is controversial. We report the case of a 76-year-old female patient with cerebral hemorrhage who received high-dose tigecycline (100 mg q12h) with other drugs for ventilator-associated pneumonia. 25 days after admission, she developed acute liver failure, mainly manifested by abnormally high bilirubin, coagulation dysfunction, and gastrointestinal hemorrhage with hemorrhagic shock. According to the updated Roussel Uclaf causality assessment method, the patient's acute liver injury was most likely caused by tigecycline.
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Antibacterianos , Fallo Hepático Agudo , Tigeciclina , Humanos , Femenino , Anciano , Tigeciclina/administración & dosificación , Tigeciclina/efectos adversos , Fallo Hepático Agudo/inducido químicamente , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Minociclina/efectos adversos , Minociclina/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Neumonía Asociada al Ventilador/tratamiento farmacológicoRESUMEN
BACKGROUND: Tigecycline-associated hypofibrinogenemia has been reported as an important adverse effect in recent years, but controlled studies minimizing confounding factors are needed. The objective of our study was to assess changes in fibrinogen levels in patients for hospitalization, comparing two antibiotic episodes (tigecycline and other) within the same patients. METHODS: The retrospective, self-controlled case series study was conducted at our University Hospitals. The study compared the change in fibrinogen levels during the patient's hospitalization for tigecycline (TigePer) and another antibiotic period (OtherPer). In addition, bleeding events, bleeding risk (determined by the IMPROVE bleeding risk score), as well as 15- and 30-day mortality rates between TigePer and OtherPer were compared. RESULTS: The study enrolled 50 patients with 100 episodes of antibiotic treatment. The median age (interquartile range) of the patients was 68.5 (21.5) years, and 38 % were female. As compared to OtherPer, TigePer had a statistically significant reduction in fibrinogen levels (p < 0.001), with a hypofibrinogenemia rate of 40 % in TigePer as compared to 2 % in OtherPer (p < 0.001). TigePer demonstrated a significantly higher 15-day mortality rate (p = 0.006). No significant differences were observed between the two periods in terms of bleeding risk, rate of bleeding events, and 30-day mortality rate (p > 0.05). CONCLUSION: Hypofibrinogenemia and other coagulopathies, without associated bleeding events, are more frequently observed in patients receiving tigecycline. Therefore, it is crucial for clinicians to monitor fibrinogen levels during tigecycline use.
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Afibrinogenemia , Humanos , Femenino , Anciano , Masculino , Afibrinogenemia/inducido químicamente , Tigeciclina/efectos adversos , Fibrinógeno/análisis , Estudios Retrospectivos , Antibacterianos/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológicoRESUMEN
INTRODUCCIÓN: El uso de tigeciclina ha ido en aumento en los últimos años, debido al incremento de la resistencia bacteriana y la escasez de alternativas terapéuticas. OBJETIVO: Caracterizar y evaluar las prescripciones de tigeciclina en pacientes internados en un hospital universitario, durante los años 2017 y 2018. METODOLOGÍA: Estudio observacional retrospectivo, donde se caracterizaron los pacientes, las terapias, la microbiología asociada, los desenlaces clínicos y las reacciones adversas asociadas a los tratamientos con tigeciclina. Se determinó la proporción de prescripciones apropiadas por un comité de expertos y el consumo de tigeciclina medido en DDD/100 camas-día. RESULTADOS: Se caracterizaron 89 pacientes, de los cuales 67 (75,3%) cumplieron los criterios de selección. El 53,7% de los pacientes eran hombres, con una edad promedio de 60 ± 15 años. El principal motivo de hospitalización fue quirúrgico (65,7%). El 67,1% de los tratamientos con tigeciclina se inició en una Unidad de Paciente Critico y el foco de infección predominante fue abdominal (64,3%). El 50% de las terapias con tigeciclina fueron dirigidas según la microbiología identificada. En 65,7% de los casos se usó tigeciclina como monoterapia en la dosis habitual (62,9%). Náuseas (8,6%), diarrea (7,1%) y vómitos (4,3%) fueron los efectos adversos más reportados. El 84,3% de los tratamientos se consideraron apropiados. El año 2017 se consumió 0,4 DDD/100 camas-día y 0,6 DDD/100 camas/día el 2018, siendo la UCI el servicio que presentó el mayor uso en ambos años. DISCUSIÓN: Tigeciclina fue utilizada principalmente en monoterapia para el tratamiento de infecciones intraabdominales en pacientes hospitalizados, por motivos quirúrgicos, en una unidad de paciente crítico, en las dosis habituales recomendadas de 100 mg como dosis de carga seguida de 50 mg cada 12 hs IV. En 50% de los casos, la terapia fue dirigida según microbiología. Los eventos adversos más habituales fueron los gastrointestinales. CONCLUSIÓN: La mayoría de las terapias prescritas fueron consideradas apropiadas por el comité de expertos.
BACKGROUND: The use of tigecycline has been increasing in recent years, due to increase in bacterial resistance and the scarcity of therapeutics alternatives. AIM: To characterize and evaluate the tigecycline prescriptions of patients hospitalized in a university hospital, during the years 2017 and 2018. METHODS: A retrospective observational study was carried out, where the patients, the therapies, the associated microbiology, the clinical outcomes and the adverse reactions associated with tigecycline were characterized. The proportion of appropriate prescriptions was determined by committee of experts and the consumption of tigecycline measure in DDD/100 bed-days. RESULTS: 89 patients who used tigecycline were characterized, of which 67 (75.3%) met the selection criteria. 53.7% of the patients were male, with a mean age of 60 +/- 15 years The main reason for hospitalization was surgical (65.7%). 67.1% of the treatments with tigecycline were started in a critical patient unit and the predominant focus of the infection was the abdomen (64.3%). 50% of the therapies with tigecycline were ordered according to the identified microbiology. In 65.7% of the cases, tigecyclin was used as monotherapy at the usual dose (62.9%). Nausea (8.6%), diarrhea (7.1%) and vomiting (4.3%) were the most reported adverse events. 84.3% of the treatments were considered appropriate. In 2017, 0.4 DDD/100 bed/days were consumed and 0.6 DDD/100 bed/days in 2018, with de ICU being the service that presented the highest use in both years. DISCUSSION: Tigecycline was mainly used as monotherapy for the treatment of intra-abdominal infections in patients hospitalized for surgical reasons in a critical patient unit at the usual doses of 100 mg loading followed by 50 mg every 12 hours IV. In 50% of the case the therapy was directed according to microbiology. The most common adverse events were gastrointestinal. CONCLUSION: Most of the prescribed therapies were considered appropriate by the expert committee.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Tigeciclina/uso terapéutico , Antibacterianos/uso terapéutico , Prescripciones de Medicamentos , Chile , Estudios Retrospectivos , Farmacorresistencia Bacteriana , Infecciones Intraabdominales/tratamiento farmacológico , Tigeciclina/administración & dosificación , Tigeciclina/efectos adversos , Hospitales Universitarios , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversosRESUMEN
INTRODUCTION: The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs. METHODS: We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without. RESULTS: This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline. CONCLUSION: A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment.
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Afibrinogenemia , Antibacterianos , Humanos , Tigeciclina/efectos adversos , Antibacterianos/efectos adversos , Estudios Retrospectivos , Fibrinolíticos/efectos adversos , Cefoperazona/efectos adversos , Sulbactam/efectos adversos , Afibrinogenemia/inducido químicamente , Afibrinogenemia/tratamiento farmacológico , Hemorragia/inducido químicamente , Fibrinógeno/efectos adversos , HemoglobinasRESUMEN
OBJECTIVE: We describe a case of acute pancreatitis (AP) and hypofibrinogenemia associated with drug treatment with the aim to increase awareness of uncommon yet possibly life-threatening adverse reactions of tigecycline and furosemide. CASE SUMMARY: A 75-year-old Chinese male was hospitalized for acute non-ST-elevation myocardial infarction and acute heart failure. The patient underwent successful percutaneous coronary intervention and MitraClip. Furosemide was taken since admission. Because Acinetobacter baumannii was detected in the blood and sputum, the patient was treated with tigecycline from the 14th day of hospitalization. Abnormal pancreatitis parameters were observed, and pancreatic CT was undertaken 12 days after the treatment of tigecycline. AP was diagnosed and symptomatic treatment was carried out, but no significant improvement was observed. On the 33rd day of hospitalization, the patient presented with acute upper gastrointestinal bleeding and decreased levels of fibrinogen and platelets. After withdrawal of tigecycline, the coagulation and pancreatitis parameters improved significantly. However, the pancreatitis parameters increased again after stopping somatostatin. Therefore, somatostatin was given again for 1 day, and furosemide was discontinued. After that, the pancreatitis parameters returned to baseline levels after a slight recovery. CONCLUSION: Clinicians should pay attention to clinical signs, symptoms, and pancreatic enzymes during tigecycline or furosemide treatment, especially when used in combination. In addition, regular monitoring of fibrinogen and platelet count during tigecycline treatment is suggested.
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Acinetobacter baumannii , Afibrinogenemia , Pancreatitis , Masculino , Humanos , Anciano , Tigeciclina/efectos adversos , Antibacterianos/efectos adversos , Afibrinogenemia/inducido químicamente , Afibrinogenemia/tratamiento farmacológico , Furosemida/uso terapéutico , Minociclina , Enfermedad Aguda , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , FibrinógenoRESUMEN
AIMS: To analyse the clinical characteristics and risk factors for tigecycline-induced pancreatitis (TIP) and evaluate the safety and efficiency of tigecycline use in non-TIP. METHODS: A retrospective case-control study was conducted on adult and juvenile patients administered tigecycline for >3 days. The adults were classified as TIP, non-TIP (pancreatitis with other causes) and non-pancreatitis. Univariate analyses were performed to compare TIP and non-pancreatitis, and multivariate analysis was used to identify risk factors for TIP. The clinical characteristics of TIP, and the safety and efficiency of tigecycline use in non-TIP were evaluated. RESULTS: A total of 3910 patients (3823 adults and 87 juveniles) were enrolled. The adult patients comprised 21 TIP, 82 non-TIP and 3720 non-pancreatitis. The TIP prevalence was 0.56% in adults and 1.15% in juveniles. The mean time from tigecycline use to symptom onset was 7.2 days, and all cases were mild pancreatitis. The mean time from tigecycline withdrawal to symptom relief was 3.6 days. The multivariate analysis identified comorbid renal insufficiency as an independent risk factor for TIP (odds ratio = 3.032). Among the 82 non-TIP patients, 81.7% had severe pancreatitis and 47.6% had necrotizing pancreatitis. The modified computed tomography severity score after tigecycline use was similar to that before tigecycline use, but the pancreatic enzymes and infection indices were significantly decreased. CONCLUSIONS: The prevalence of TIP was low. Comorbid renal insufficiency was as an independent risk factor for TIP. Tigecycline is safe and efficient for treatment of pancreatitis, especially necrotizing pancreatitis, with intra-abdominal infection.
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Antibacterianos , Pancreatitis Aguda Necrotizante , Adulto , Humanos , Antibacterianos/efectos adversos , Tigeciclina/efectos adversos , Estudios Retrospectivos , Estudios de Casos y Controles , Centros de Atención Terciaria , Factores de Riesgo , Pancreatitis Aguda Necrotizante/inducido químicamente , Pancreatitis Aguda Necrotizante/tratamiento farmacológicoRESUMEN
BACKGROUND: and Purpose: Colorectal cancer (CRC) is one of the cancers with the highest incidence in which APC gene mutations occur in almost 80% of patients. This mutation leads to ß-catenin aberrant accumulation and an uncontrolled proliferation. Apoptosis evasion, changes in the immune response and microbiota composition are also events that arise in CRC. Tetracyclines are drugs with proven antibiotic and immunomodulatory properties that have shown cytotoxic activity against different tumor cell lines. EXPERIMENTAL APPROACH: The effect of tigecycline was evaluated in vitro in HCT116 cells and in vivo in a colitis-associated colorectal cancer (CAC) murine model. 5-fluorouracil was assayed as positive control in both studies. KEY RESULTS: Tigecycline showed an antiproliferative activity targeting the Wnt/ß-catenin pathway and downregulating STAT3. Moreover, tigecycline induced apoptosis through extrinsic, intrinsic and endoplasmic reticulum pathways converging on an increase of CASP7 levels. Furthermore, tigecycline modulated the immune response in CAC, reducing the cancer-associated inflammation through downregulation of cytokines expression. Additionally, tigecycline favored the cytotoxic activity of cytotoxic T lymphocytes (CTLs), one of the main immune defenses against tumor cells. Lastly, the antibiotic reestablished the gut dysbiosis in CAC mice increasing the abundance of bacterial genera and species, such as Akkermansia and Parabacteroides distasonis, that act as protectors against tumor development. These findings resulted in a reduction of the number of tumors and an amelioration of the tumorigenesis process in CAC. CONCLUSION AND IMPLICATIONS: Tigecycline exerts a beneficial effect against CRC supporting the use of this antibiotic for the treatment of this disease.
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Antineoplásicos , Neoplasias Colorrectales , Animales , Ratones , Tigeciclina/efectos adversos , beta Catenina/metabolismo , Neoplasias Colorrectales/genética , Carcinogénesis , Transformación Celular Neoplásica/metabolismo , Vía de Señalización Wnt , Antineoplásicos/efectos adversos , Inmunidad , Antibacterianos/efectos adversos , Proliferación CelularRESUMEN
BACKGROUND: Identification of tumor dependencies is important for developing therapeutic strategies for liver cancer. METHODS: A genome-wide CRISPR screen was performed for finding critical vulnerabilities in liver cancer cells. Compounds screen, RNA sequencing, and human phospho-receptor tyrosine kinase arrays were applied to explore mechanisms and search for synergistic drugs. FINDINGS: We identified mitochondrial translation-related genes associated with proliferation for liver cancer cells. Tigecycline induced deficiency of respiratory chain by disturbing mitochondrial translation process and showed therapeutic potential in liver cancer. For liver cancer cells extremely insensitive to tigecycline, a compounds screen was applied to identify MEK inhibitors as synergistic drugs to tigecycline-insensitive liver cancer cells. Mechanistically, sustained activation of EGFR-ERK1/2-MYC cascade conferred the insensitivity to tigecycline, which was mediated by enhanced secretion of EREG and AREG. Moreover, glycolytic enzymes, such as HK2 and PKM2 were upregulated to stimulate glycolysisin a MYC-dependent manner. Tigecycline induced respiratory chain deficiency in combination with cutting off EGFR-ERK1/2-MYC cascade by MEK inhibitors or EGFR inhibitors, resulting in decrease of both oxidative phosphorylation and glycolysis in liver cancer cells. INTERPRETATION: Our study proved that blocking EGFR-ERK1/2-MYC cascade combined with tigecycline could be a potential therapeutic strategy for liver cancer. FUNDING: This work was funded by grants from the National Natural Science Foundation of China (82073039,82222047, 81920108025), Program of Shanghai Academic/Technology Research Leader (22XD1423100), Shanghai Municipal Science and Technology Project (20JC1411100), 111 Project (B21024), Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZDCX20212700, SHSMU-ZDCX20210802) and Shanghai Jiao Tong University School of Medicine (YG2019GD01).
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Neoplasias Hepáticas , Sistema de Señalización de MAP Quinasas , Humanos , Tigeciclina/efectos adversos , Línea Celular Tumoral , China , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Inhibidores de Proteínas Quinasas/efectos adversos , Receptores ErbB/genética , Quinasas de Proteína Quinasa Activadas por MitógenosRESUMEN
Knowledge regarding the association between hypofibrinogenemia and tigecycline is based mainly on case reports. However, the clinical features of tigecycline-induced hypofibrinogenemia are unclear. We collected 20 patients (16 males and 4 females) with tigecycline-induced hypofibrinogenemia by searching the Chinese and English databases from June 2005 to May 2021, with a median age of 63.5 years (range 39â¼90 years). Hypofibrinogenemia developed at a median of 9 days (range 2â¼35 days). Most patients had no typical clinical manifestations, and only a few patients had bleeding and ecchymosis. Fibrinogen levels gradually decreased from 3.98 ± 2.05 g/L to 0.87 ± 0.45 g/L (P = 0.000), and the activated partial thromboplastin time (APTT) increased from 38.26 ± 8.80 s to 83.43 ± 47.23 s (P = 0.002). Fibrinogen levels in all patients recovered to the normal range within a median of 4 days (range 1â¼12 days) after tigecycline cessation. Our results suggest that fibrinogen levels should be closely monitored in patients treated with tigecycline, specifically patients who may have renal insufficiency or patients with long-term use.
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Afibrinogenemia , Insuficiencia Renal , Tigeciclina , Adulto , Femenino , Humanos , Masculino , Afibrinogenemia/inducido químicamente , Fibrinógeno , Insuficiencia Renal/inducido químicamente , Tigeciclina/efectos adversos , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
OBJECTIVES: This study aimed to determine the thresholds of serum concentration as a predictor of tigecycline (TGC)-induced hypofibrinogenemia (HF) in critically ill patients. METHODS: A retrospective cohort study was conducted in intensive care unit patients treated with TGC. The clinical data and serum concentration were extracted from the patients' electronic medical records. Patients were divided into an HF group and a normal group according to fibrinogen value. The receiver operating characteristic curves and logistic regression were used to derive serum concentration thresholds and quantify the association between exposure thresholds and HF while adjusting for confounders. RESULTS: In total, 100 patients were included. The receiver operating characteristic curves analysis showed that TGC concentration parameters were strongly predictive of HF. Adjusting for duration of TGC, serum concentration at the 6 hours after the dosing (C1/2) ≥ 0.645 mg/l, area under the concentration-time curve over a 24-hour period (AUC 0-24) ≥ 20.76 mg·h/l, and serum concentration of 30 minutes before next dose (Cmin) ≥ 0.455 mg/l were associated with a three- to five-fold increased risk of TGC-induced HF in logistic regression. CONCLUSION: The findings from this study provide evidence that TGC exposure is highly predictive of HF, with an approximately three- to five-fold increased risk. Serum concentration at the 6 hours after the dosing (C1/2) ≥ 0.645 mg/l with best area under the receiver operating characteristic curve and negative predictive value appears to be the most appropriate toxicity threshold.
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Afibrinogenemia , Enfermedad Crítica , Tigeciclina , Afibrinogenemia/inducido químicamente , Afibrinogenemia/tratamiento farmacológico , Antibacterianos/efectos adversos , Fibrinógeno , Humanos , Estudios Retrospectivos , Tigeciclina/efectos adversosRESUMEN
INTRODUCTION: The purpose of this study was to assess clinical characteristics and risk factors for tigecycline-associated prothrombin time (PT) and activated partial thromboplastin time (aPTT) prolongation. METHODS: We performed a retrospective analysis on coagulation parameters before and during tigecycline treatment in 55 patients in our hospital with severe infections, mainly pneumonia caused by Acinetobacter baumannii. Patients were divided into different groups according to prolongation of PT and aPTT, and clinical features involved were explored. Univariate and multivariable binary logistic regression analyses were used to identify risk factors for tigecycline-associated PT and aPTT increase. RESULTS: We found that PT values increased from 12.73 ± 1.87 to 13.86 ± 2.06 during the treatment compared with premedication (p < 0.001), and the aPTT level prolonged significantly from 33.63 ± 11.24 to 38.15 ± 11.81 (p < 0.001). The multivariate analyses identified 2 variables that were associated with tigecycline-induced PT prolongation: albumin level (p = 0.018) and weight-adjusted tigecycline dosage (p = 0.005). In addition, treatment duration was the only risk factor for tigecycline-induced aPTT prolongation (p = 0.043). CONCLUSION: Albumin level, weight-adjusted tigecycline dosage, treatment duration may serve as risk indicators for tigecycline-associated coagulation dysfunction. Physicians should be careful with coagulation disorder when prescribing tigecycline in clinical practice, especially in patients with risk factors.
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Trastornos de la Coagulación Sanguínea , Albúminas , Trastornos de la Coagulación Sanguínea/inducido químicamente , Humanos , Tiempo de Tromboplastina Parcial , Estudios Retrospectivos , Tigeciclina/efectos adversosRESUMEN
Tigecycline is a broad-spectrum antibacterial agent. As the incidence of multidrug-resistant bacterial infections has increased in intensive care units (ICUs) over the past decades, tigecycline is often used in ICUs. Information about tigecycline-associated hepatotoxicity in ICU patients is limited. To investigate the potential risk factors for tigecycline-associated hepatotoxicity in ICU patients, 148 patients from 2 centers who had received tigecycline for at least 4 days were retrospectively analyzed. Hepatotoxicity was classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5.0) grading system. As a result, 33.8% of patients experienced hepatotoxicity events in the ICU. The multivariate analysis showed that an albumin concentration <25 g/L at baseline (odds ratio, 3.714; 95%CI, 1.082-12.744; P = .037) and treatment duration (odds ratio, 1.094; 95%CI, 1.032-1.160; P = .003) were significantly correlated with tigecycline-associated hepatotoxicity. The median time to onset of hepatotoxicity was 8.0 days. The median duration ICU stay and the in-hospital mortality rate were not different between the hepatotoxicity group and the nonhepatotoxicity group (33.5 days (interquartile range, 21.0-72.0) vs 31.0 days (interquartile range, 21-62.5), P = .850; 38.0% vs 43.8%; P = .504). Therefore, close monitoring of liver function is recommended for patients with baseline albumin concentrations <25 g/L or for patients who receive tigecycline therapy for >8 days.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Unidades de Cuidados Intensivos , Albúminas , Antibacterianos , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Humanos , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria , Tigeciclina/efectos adversosRESUMEN
INTRODUCTION: We conducted a drug use investigation to investigate the safety and efficacy of tigecycline, which has been approved for clinical use for the treatment of multidrug-resistant gram-negative infections in Japan. METHODS: This was an open-label, observational, multicenter cohort study that included all patients who received tigecycline. RESULTS: A total of 116 patients were registered between December 2012 and April 2016 and all of them were evaluated for safety and efficacy. Among them, 64 patients aged ≥65 years (55.2%) and five children aged <15 years (4.3%) were included. Of these patients, 47 (40.5%) met the approved indications of tigecycline. Adverse drug reactions (ADRs) were observed in 41 patients (35.3%) with a total of 74 events. Serious ADRs were observed in 15 patients (12.93%) with a total of 33 events. There were 42 deaths, and 6 of these were considered to be caused by ADRs. Among the 116 patients, 65 achieved clinical response at the end of the observation period, and the efficacy rate was 73.9%. Furthermore, 46 patients were assessed as "cure" at the test of cure visit, and the cure rate was 59.0%. The eradication rate was 47.5% at the end of the observation period. Classified by pathogenic bacteria, the eradication rate of patients infected with the approved pathogens was 54.5%. CONCLUSIONS: Tigecycline was well-tolerated, and no additional safety concerns were noted. It was effective considering that most patients had poor physical conditions. The overall benefit-risk balance of tigecycline was favorable.
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Antibacterianos , Vigilancia de Productos Comercializados , Antibacterianos/efectos adversos , Niño , Estudios de Cohortes , Humanos , Japón/epidemiología , Tigeciclina/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: We conducted this multicenter retrospective study to evaluate the prevalence, clinical patterns, and risk factors for tigecycline-induced liver injury, which is a type of drug-induced liver injury (DILI). METHODS: Inpatients receiving intravenous tigecycline for ≥7 days were included. Patient information was collected to assess possible DILIs. The pattern and severity of tigecycline DILI were evaluated. A multivariable logistic regression model was used to identify the independent risk factors associated with tigecycline DILI. RESULTS: A total of 986 patients were identified and 397 patients were included in this study. The prevalence of tigecycline DILI was 10.3% (95% confidence interval [CI] = 7.51-13.7%). The most common type of tigecycline DILI was cholestatic, with mild severity observed in most cases. Abnormal baseline alanine aminotransferase levels (odds ratio [OR] = 3.11, 95% CI = 1.55-6.24, P = 0.001), intensive care unit admission (OR = 2.63, 95% CI = 1.32-5.36, P = 0.006), and treatment length (in weeks) (OR = 1.25, 95% CI = 1.05-1.49, P = 0.011) were independent risk factors for tigecycline DILI. CONCLUSION: Our results indicate that the prevalence of tigecycline DILI is high, and that the patients at risk should receive special attention.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Humanos , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Tigeciclina/efectos adversosRESUMEN
BACKGROUND: There have been no reports of tigecycline-associated drug-related liver injury (DILI) identified by histopathological assistance and causal assessment method. We reported the histopathological manifestations for the first time and described tigecycline-associated liver injury's pattern, severity, duration, and outcome. CASE PRESENTATION: A 68-year-old male with post-liver transplantation was given high-dose tigecycline intravenously (loading dose 200 mg, followed by 100 mg every 12 h) combined with polymyxin B (50,000 units by aerosol inhalation every 12 h) for hospital-acquired pneumonia caused by carbapenem-resistant Klebsiella pneumoniae. At the same time, tacrolimus was discontinued. Liver function was initially normal but started to decline on day 4 of tigecycline. Reducing the dose of tigecycline and resuming tacrolimus could not reverse the deterioration. Therefore, a liver puncture biopsy was performed for further diagnosis, with histopathological findings being cytotoxic injury. The updated RUCAM scale was used to evaluate the causal relationship between tigecycline and liver injury, with the result of 7 points indicating a "probable" causality grading. Methylprednisolone was initiated to treat DILI that was determined to be Grade 1 cholestatic injury. Total bilirubin and transaminase levels returned to normal on day 4 and 11 after tigecycline withdrawal, respectively. Monthly outpatient follow-up showed that the patient's liver function stayed normal. CONCLUSIONS: This case possessed a significant reference value for differential diagnosis and treatment prognosis of tigecycline-associated DILI. With early diagnosis and timely management, the tigecycline-associated DILI of this patient was successfully reversed.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Anciano , Causalidad , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Humanos , Klebsiella pneumoniae , Masculino , Tigeciclina/efectos adversosRESUMEN
BACKGROUND: Tigecycline is the first member of the glycylcyclines. Both the FDA (2010 and 2013) and the EMA (2011) issued safety warnings describing an increased mortality risk associated with tigecycline compared with other antibiotics treating severe infections. One of the best strategies to optimize antimicrobial therapies is through the establishment of antimicrobial stewardship programmes (ASPs) in hospitals. In June 2011, our ASP was implemented. OBJECTIVES: To analyse trends in tigecycline prescription, after drug safety warning announcements by regulatory agencies and after an ASP implementation. METHODS: A 6â year prospective observational study of tigecycline use was performed, including all consecutive adult patients treated with at least one dose during the 6â years after approval of the drug for its use in the hospital. The primary outcome was tigecycline consumption assessed by DDD/100 bed-days. A segmented linear regression model for interrupted time series (ITS) was designed to detect any significant trend changes. RESULTS: A total of 524 patients were included. After the FDA warning alert, tigecycline consumption decreased by 35.9%. Moreover, following the ASP implementation, a dramatic reduction in tigecycline prescription by 67.3% was observed. CONCLUSIONS: The role of the ASP was essential to establish adequate control of prescriptions, collaborating with the clinicians in a better adaptation of the tigecycline indication.