Efficacy and safety analysis of tigecycline and polymyxin B in the treatment of carbapenem-resistant enterobacteriaceae pneumonia in critically ill patients / 中国临床药理学与治疗学

AIM: To compare the efficacy and safety of tigecycline with polymyxin B in the treatment of carbapenem resistant enterobacteriaceae (CRE) pneumonia in critically ill patients. METHODS: A retrospective analysis was performed on the clinical data of patients with CRE pneumonia who received tigecycline or polymyxin B therapy from January 1, 2018 to Jun 30, 2023 in the Intensive Care Unit (ICU). Primary outcomes included the 28-day all-cause mortality and clinical cure rate within 28days. Secondary outcomes included the ICU mortality, in-hospital mortality, the length of hospital stay and ICU stay, microbial eradication, duration of mechanical ventilation. Independent predictors affecting 28-day clinical cure rate were tested using Cox regression analyses. RESULTS: A total of 83 eligible patients were included in the final analysis after propensity score matching, 54 in the tigecycline group and 29 in the polymyxin B group. The 28-day all-cause mortality was 31.5% (17/54) in the tigecycline group and 37.9% (11/29) in the polymyxin B group, the difference was not statistically significant (P=0.554); the clinical cure rate was 63% (34/ 54) in the tigecycline group, which was significantly higher than that of the polymyxin B group of 34.5% (10/29) (P = 0.013). There were no statistical differences between the two groups in terms of secondary outcomes. Multivariate logistic regression analysis found that the use of tigecycline was an independent predictor of the 28-day clinical cure rate (HR 2.083, 95%CI 1.018-4.263, P = 0.045). However, activated partial thromboplastin time (APTT) and prothrombin time (PT) were significantly prolonged in the tigecycline group compared with the polymyxin B group (P=0.047; P=0.027), and fibrinogen (FIB) was significantly decreased (P < 0.001) after drug administration. CONCLUSION: There was no significant difference in 28-day all-cause mortality between the tigecycline and polymyxin groups; tigecycline might be associated with a higher 28-day clinical cure rate compared with polymyxin B. It should be noted that tigecycline may increase the risk of coagulation abnormalities.

Anti-infection treatment and pharmaceutical care for a patient with severe pneumonia caused by Chlamydia psittaci / 中国药房

OBJECTIVE To provide ideas and reference for the anti-infection treatment and pharmaceutical care for severe pneumonia caused by Chlamydia psittaci. METHODS Clinical pharmacists participated in the whole process of the treatment for a patient with C. psittaci-induced severe pneumonia. According to the patient’s medical history， clinical symptoms and test results， clinical pharmacists assisted the physician to dynamically adjust the anti-infective scheme； for C. psittaci infection， the patient was treated with tigecycline combined with azithromycin successively， and other infection therapy plans were dynamically adjusted according to the results of pathogen examination. During the treatment， the patient suffered from suspicious adverse drug reactions such as prolonged QTc interval， elevated lipase and amylase； the clinical pharmacists conducted pharmaceutical care and put forward reasonable suggestions. RESULTS The physician adopted the pharmacists’ suggestion， and the patient was discharged after treatment. CONCLUSIONS For the treatment of severe pneumonia caused by C. psittaci， the characteristics of patients， drugs and pathogens should be taken into account to develop individualized anti-infective treatment. Tetracyclines and macrolides have a definite effect on C. psittaci infection， but attention should be paid to the possible ADR caused by drugs in clinical application.

Research hotspots and trends of tigecycline drug resistance: A study based on CiteSpace / 公共卫生与预防医学

Objective To explore the research progress, research hotspot and development trend of tigecycline resistance based on the quantitative analysis and visualization function of CiteSpace. Methods The data were collected from 4,263 Chinese and English articles on tigecycline resistance in CNKI, Wanfang, VIP and Web of Science (WOS) databases from 2012 to 2022. CiteSpace 5.8.R3 software was used to analyze the cooperative network of authors, the cooperative network of countries and institutions, the total citation times of journals, and keywords included in the literature, to reveal the hotspots and trends of tigecycline resistance research. Results The number of articles published in English literature was higher than that in Chinese literature. China had the largest number of published documents, showing a significant international academic influence in this research field. Countries all over the world were concerned about the resistance of tigecycline, but Chinese literatures focused more on the clinical infection and prevention of tigecycline resistance, while English literatures placed special emphasis on the research about the drug resistance mechanism of tigecycline. Conclusion The research direction at home and abroad is basically the same, but the research focus has gradually shifted from the clinical treatment and monitoring of tigecycline to the molecular level of drug resistance mechanism.

Perfil de uso de tigeciclina en un hospital universitario en Chile / Profile of tigecycline use in a university hospital in Chile

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.

Unveiling the genome of a high-risk pandrug-resistant Klebsiella pneumoniae emerging in the Brazilian Amazon Region, 2022

BACKGROUND Pandrug-resistant (PDR) Klebsiella pneumoniae has been reported sporadically in many countries and remains rare in Brazil. OBJECTIVES This study unravelled the genetic determinants involved with the PDR background of a clinical ST11 K. pneumoniae recovered in the Brazilian Amazon Region, where K. pneumoniae genomic and epidemiological information is scarce. METHODS Kp196 was submitted to the antimicrobial susceptibility test by the disk-diffusion method and minimum inhibitory concentration (MIC) determination. The whole genome sequencing was obtained and the sequence type was determined by core genome multilocus sequence typing (cgMLST). Its intrinsic and acquired resistome was assessed by Comprehensive Antibiotic Resistance Database (CARD) and comparison with wild-type genes. FINDINGS The analyses revealed that Kp196 belonged to the pandemic ST11 and presented the PDR phenotype. Its acquired resistome was composed of a huge set of clinically relevant resistance determinants, including bla CTX-M-15 and bla NDM-1, all found in the vicinity of mobile platforms. Considering its intrinsic resistome, the multidrug resistance, especially to colistin, tigecycline and fluoroquinolones, was multifactorial and attributed to modifications (indels, missense mutations, and gene disruption) in several housekeeping genes (arnT/phoQ/mgrB/ramR/acrB/gyrA/parC/ompK35-36-37). The Kp196 intrinsic resistome was also observed in a ST11 environmental strain, although harbouring distinct acquired resistomes. CONCLUSIONS An accumulation of different resistance mechanisms regarding the intrinsic resistome accounts for a more stable resistome, strongly contributing to the Kp196 PDR phenotype.

Efficacy of perioperative use of tigecycline in preventing infection and incidence of hypofibrinogenemia in liver transplant recipients / 器官移植

Objective To evaluate the efficacy of perioperative use of tigecycline in preventing infection and the incidence of hypofibrinogenemia in liver transplant recipients. Methods Clinical data of 40 liver transplant recipients given with tigecycline to prevent infection were retrospectively analyzed. The incidence of infection in recipients and donor-derived infection were analyzed. The changes of clinical indexes in recipients during, upon the completion and (7±2) d after tigecycline treatment were analyzed, respectively. The incidence and treatment of hypofibrinogenemia were summarized. Results Among 40 liver transplant recipients, 2 cases were infected by aspergillus niger and cytomegalovirus, out of the antibacterial spectrum of tigecycline. After adjusting the anti-infection regimen, the infection was properly controlled. Liver allografts were positive for relevant culture in 9 cases, whereas none of them progressed into donor-derived infection. Approximately at postoperative 2 weeks, all 40 recipients restored liver function and were discharged from hospital. Among them, 6 recipients developed hypofibrinogenemia complicated with coagulation disorder at postoperative 2-4 d, whereas transaminase level, bilirubin level and infection-related indexes were gradually decreased after liver transplantation, and albumin level was stable. After supplemented with human fibrinogen and prothrombin complex, coagulation function was improved, but fibrinogen level persistently declined. After terminating use of tigecycline, fibrinogen level was gradually restored to normal range, which might be an adverse drug reaction induced by tigecycline. Conclusions Perioperative anti-infection regimen including tigecycline may reduce the incidence of infection caused by sensitive bacteria in liver transplant recipients. Nevertheless, the incidence of hypofibrinogenemia should be intimately monitored throughout the use of tigecycline.

The pharmaceutical care of a multidrug-resistant bacterial infection patient with tigecycline-induced hypofibri-nogenemia / 中国药房

OBJECTIVE To provide reference for pharmaceutical care of multidrug-resistant bacterial infection patients with tigecycline-induced hypofibrinogenemia and the safe use of tigecycline. METHODS Clinical pharmacists participated in a case of hypofibrinogenemia caused by tigecycline with multidrug-resistant bacterial infection， to determine the correlation of hypofibrinogenemia and tigecycline， and to analyze the risk factors and possible mechanisms of the occurrence of hypofibrinogenemia caused by tigecycline in combination with relevant literature. Clinical pharmacists recommended that physicians discontinued tigecycline and provided human fibrinogen and plasma for correction. RESULTS & CONCLUSIONS Tigecycline was associated with hypofibrinogenemia of the patient. The physician followed the advice of clinical pharmacists and the patient’s fibrinogen level returned to normal. The risk factors of hypofibrinogenemia induced by tigecycline included high dose， long course of treatment， and complication with renal dysfunction. Clinical pharmacists should timely advise physicians to stop taking the drug， and give human fibrinogen and blood product infusion for correction when necessary， so as to avoid the occurrence of serious life- threatening coagulation disorders and ensure the safety of tigecycline use.

Synergistic effect of β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli in vitro / 生物工程学报

The widespread of tigecycline resistance gene tet(X4) has a serious impact on the clinical efficacy of tigecycline. The development of effective antibiotic adjuvants to combat the looming tigecycline resistance is needed. The synergistic activity between the natural compound β-thujaplicin and tigecycline in vitro was determined by the checkerboard broth microdilution assay and time-dependent killing curve. The mechanism underlining the synergistic effect between β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli was investigated by determining cell membrane permeability, bacterial intracellular reactive oxygen species (ROS) content, iron content, and tigecycline content. β-thujaplicin exhibited potentiation effect on tigecycline against tet(X4)-positive E. coli in vitro, and presented no significant hemolysis and cytotoxicity within the range of antibacterial concentrations. Mechanistic studies demonstrated that β-thujaplicin significantly increased the permeability of bacterial cell membranes, chelated bacterial intracellular iron, disrupted the iron homeostasis and significantly increased intracellular ROS level. The synergistic effect of β-thujaplicin and tigecycline was identified to be related to interfere with bacterial iron metabolism and facilitate bacterial cell membrane permeability. Our studies provided theoretical and practical data for the application of combined β-thujaplicin with tigecycline in the treatment of tet(X4)-positive E. coli infection.

Retrospective analysis of coagulopathy in patients with severe renal insufficiency caused by tigecycline / 中国药房

OBJECTIVE To analyze the effects of tigecycline on coagulation function in patients with severe renal insufficiency， and to provide a reference for safe clinical drug use. METHODS Retrospective analysis was performed for the clinical data of patients with severe renal dysfunction complicated with infection receiving tigecycline admitted to nephrology department of our hospital from January 2021 to October 2022. The levels of prothrombin time （PT）， activated partial thromboplastin time （APTT）， international normalized ratio （INR）， platelet （PLT） and fibrinogen （FIB） were compared 3 days before medication， with 1-5， 6-10， 11-15 and 16-20 days after medication， 5 days after withdrawal and/or after symptomatic treatment. RESULTS Finally， 14 patients were included， and 9 patients developed coagulopathy， with an incidence of 64.29%. Compared with 3 days after medication， the levels of FIB at 6-10 and 11-15 days after medication， and PLT at 1-5 ， 6-10 and 11- 15 days after medication were decreased significantly， while the levels of PT at 1-5 and 6-10 days after medication， APTT at 1-5， 6-10 and 11-15 days after medication were significantly prolonged， and INR increased significantly at 1-5 and 6-10 days after medication （P＜0.05）. Compared with 3 days before medication， there were no statistically significant changes in FIB， PT， INR， APTT and PLT at 16-20 days after medication and 5 days after withdrawal and/or symptomatic treatment（P＞0.05）. CONCLUSIONS Patients with severe renal insufficiency should be cautious with tigecycline， which can lead to prolonged PT and APTT， increased INR， and decreased PLT and FIB. If medication time is over 14 days， dynamic monitoring of coagulation function indicators is recommended to reduce the risk of adverse reactions.

Capacidade de formação de biofilmes e perfil de resistência de Acinetobacter baumannii isolados em unidades de terapia intensiva: uma revisão sistemática

Introdução: Acinetobacter baumanni é um cocobacilo Gram negativo responsável por elevadas taxas de infecções relacionadas à assistência à saúde (IRAS). Apresenta alto nível de resistência intrínseca a antimicrobianos, além da capacidade de adquirir resistência a carbapenêmicos e polimixinas. Ainda, A. baumannii possui habilidade para produzir biofilmes em superfícies abióticas e bióticas, o que favorece a infecção de pacientes gravemente enfermos internados em unidades de terapia intensiva (UTI). Deve ser ressaltado que bactérias envolvidas em biofilmes apresentam maior resistência aos antimicrobianos, atribuída a fatores bioqúmicos, moleculares e as condições dos hospedeiros, o que dificulta o tratamento dessas infecções. Objetivos: Avaliar a produção de biofilme por isolados de A. baumannii recuperados de pacientes internados em UTIs, bem como operfil de susceptibilidade a antimicrobianos (aminoglicosídeos, tigeciclina, carbapenêmicos e polimixinas) entre esses isolados. Métodos: Foi realizada uma revisão sistemática de acordo com os critérios Prisma nos bancos de dados Pubmed/Medline, Scopus, Lilacs, Scielo, e Web of Science. Resultados: Foram incluídos um total de 12 artigos que avaliaram 1006 isolados clínicos de A. baumannii, os quais todos foram resistentes aos carbapenê-micos. No entanto, a maioria dos isolados permaneceu sensível as polimixinas B e E(94,46%). A porcentagem dos isolados produtores de biofilme foi alta (96,3%), e neste estudo não fica clara a relação entre a habilidade de produzir biofilmes e a resistência aos antimicrobianos analisados. Conclusão: Mais estudos devem ser conduzidos para monitorar a resistência aos antimicrobianos em A. baumannii, sobretudo em produtores de biofilme, visto que o manejo terapêutico das infecções ocasionadas por essas linhagens torna-se mais complexo e desafiador.

SUMMARY Introduction: Acinetobacter baumanni is a Gram-negative coccobacillus responsible for high rates of healthcare-related infections (HAI). It has a high level of intrinsic resistance to antimicrobials, in addition to the ability to acquire resistance to carbapenems and polymyxins. Furthermore, A. baumannii has the ability to produce biofilms on abiotic and biotic surfaces, which favors the infection of critically ill patients admitted to intensive care units (ICU). It should be noted that bacteria involved in biofilms have greater resistance to antimicrobials, attributed to biochemical and molecular factors and the conditions of the hosts, which makes the treatment of these infections difficult. Objectives: To evaluate the biofilm production by A. baumannii isolates recovered from ICU patients, as well as the antimicrobial susceptibility profile (aminoglycosides, tigecycline, carbapenems and polymyxins) among these isolates. Methods: A systematic review was performed according to PRISMA criteria in the PUBMED/MEDLINE, Scopus, LILACS, SciELO, and Web of Science databases. Results: A total of 12 articles that evaluated 1006 clinical isolates of A. baumannii, all of which were resistant to carbapenems, were included. However, most isolates remained sensitive to polymyxins B and E (94.46%). The percentage of biofilm-producing isolates was high (96.3%), and in this study the relationship between the ability to produce biofilms and resistance to the analyzed antimicrobials is not clear. Conclusion: More studies should be conducted to monitor antimicrobial resistance in A. baumannii, especially in biofilm producers, as the therapeutic management of infections caused by these strains becomes more complex and challenging.

Introducción: Acinetobacter baumanni es un cocobacilo gramnegativo responsable de altas tasas de infecciones relacionadas con la salud. Tiene un alto nivel de resistencia intrínseca a los antimicrobianos, además de la capacidad de adquirir resistencia a los carbapenémicos y polimixinas. Además, A. baumannii tiene la capacidad de producir biopelículas en superficies abióticas y bióticas, lo que favorece la infección de pacientes críticos ingresados en unidades de cuidados intensivos (UCI). Cabe señalar que las bacterias involucradas en biofilms tienen mayor resistencia a los antimicrobianos, atribuida a factores bioquímicos y moleculares y a las condiciones de los hospedadores, lo que dificulta el tratamiento de estas infecciones. Objetivos: Evaluar la producción de biofilm por aislamientos de A. baumannii recuperados de pacientes de UCI, así como el perfil de susceptibilidad antimicrobiana (amino-glucósidos, tigeciclina, carbapenémicos y polimixinas) entre estos aislamientos. Métodos: Se realizó una revisión sistemática según los criterios Prisma en las bases de datos Pubmed / Medline, Scopus, Lilacs, SciELO y Web of Science. Resultados: Se incluyeron un total de 12 artículos que evaluaron 1006 aislamientos clínicos de A. baumannii, todos ellos resistentes a carbapenémicos. Sin embargo, la mayoría de los aislados permanecieron sensibles a las polimixinas B y E (94,46%). El porcentaje de aislamientos productores de biopelículas fue alto (96,3%), y en este estudio no está clara la relación entre la capacidad de producir biopelículas y la resistencia a los antimicrobianos analizados. Conclusión: Se deben realizar más estudios para monitorear la resistencia a los antimicrobianos en A. baumannii, especialmente en productores de biopelículas, ya que el manejo terapéutico de las infecciones causadas por estas cepas se vuelve más complejo y desafiante.

Mechanisms involved in resistance to carbapenems among Acinetobacter baumannii isolates recovered in Brazil: A systematic review and meta-analysis

SUMMARY Introduction: Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a health problem due to the limited therapeutic options available. This study was carried out to evaluate the main mechanisms of resistance of carbapenems in CRAB in the last 10 years in Brazil and to describe the susceptibility profile to tigecycline and polymyxins in these isolates. Material and methods: A systematic review was carried out according to Prisma in PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) and Cochrane Library. Data regarding enzyme resistance to carbapenems were evaluated by meta-analysis according to the random effect. Results: 21 articles were selected according to inclusion and exclusion criteria that evaluated 1096 CRAB. Most of the studies were carried out in the southern (33.3 %) and southeast (23.8 %) regions of Brazil (33.3 %) and in 2016 and 2018. According to the meta-analyzes, OXA-type carbapenemase was the main mechanism involved in the low susceptibility to carbapenems in CRAB (98%; 95% CI: 0.91, 0.99; I2 = 95%), with bla OXA-23-like (91 %; 95 % CI: 0.76; 0.97; I2 = 97 %) or bla OXA-51-like / ISAba1 (84 %; 95 % CI: 0.15, 0.99; I2 = 98 %) genes, followed by metallo-ß-lactamases (MBL) (12 %, 95 % CI: 0.09, 0.15, I2 = 99 %) and Klebsiella pneumoniae carbapenemase (KPC) (6 %, 95 % CI: 0.04; 0.08; I2 = 87 %). Conclusion: The included studies showed that susceptibility to colistin (99 %) and tigecy-cline (93 %) remains high and was not affected by carbapenem resistance.

Introducción: Las infecciones por Acinetobacter baumannii resistente a carbapenémicos (CRAB) es un problema de salud debido a las limitadas opciones terapéuticas disponibles. Este estudio se realizó para evaluar los principales mecanismos de resistencia de los carbapenémicos en CRAB en los últimos 10 años en Brasil y describir el perfil de susceptibilidad a tigeciclina y polimixinas en estos aislados. Material y métodos: Se realizó una revisión sistemática de acuerdo con Prisma en PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) y Cochrane Library. Los datos referentes a resistencia enzimática a los carbapenémicos se evaluaron mediante metaanálisis según el efecto aleatorio. Resultados: Se seleccionaron 21 artículos según criterios de inclusión y exclusión que evaluaron 1.096 CRAB. La mayoría de los estudios se llevaron a cabo en las regiones sur (33,3%) y sureste (23,8 %) de Brasil (33,3 %) y en los años 2016 y 2018. Según los metaanálisis, la carbapenemasa tipo OXA fue el principal mecanismo implicado en la baja susceptibilidad a los carbapenémicos en CRAB (98 %; IC 95 %: 0,91; 0,99; I² = 95 %), con bla OXA-23-like (91 %; 95 % CI: 0,76; 0,97; I² = 97 %) o bla OXA-51-like / ISAba1 (84 %; 95 % CI: 0,15; 0,99 ; I² = 98 %) genes, seguida de metalo-ß-lactamasas (MBL ) (12 %; IC95 %: 0,09; 0,15; I² = 99 %) y Klebsiella pneumoniae carbapenemase (KPC) (6 %; IC95 %: 0,04; 0,08; I² = 87 %). Conclusión: Los estudios incluidos mostraron que la susceptibilidad a la colistina (99 %) y tigeciclina (93 %) sigue siendo alta y no se ve afectada por la resistencia a los carbapenémicos.

Introdução: As infecções causadas por Acinetobacter baumannii resistente aos carbapenémicos (CRAB) são um problema de saúde devido às limitadas opções terapêuticas disponíveis. Este estudo foi realizado para avaliar os principais mecanismos de resistência aos carbapenêmicos em CRAB nos últimos 10 anos no Brasil e descrever o perfil de susceptibilidade à tigeciclina e às polimixinas nesses isolados. Material e métodos: Foi conduzida uma revisão sistemática segundo o Prisma nas bases de dados PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) e Biblioteca Cochrane. Os dados relativos à resistência enzimática aos carbapenêmicos foram avaliados por meta-análises de acordo com o efeito aleatório. Resultados: Foram selecionados 21 artigos de acordo com os critérios de inclusão e exclusão que avaliaram 1.096 CRAB. A maioria dos estudos foi realizada nas regiões Sul (33,3 %) e Sudeste (23,8 %) do Brasil e nos anos de 2016 e 2018. De acordo com as metanálises, a carbapenemase do tipo OXA foi o principal mecanismo envolvido na baixa susceptibilidade aos carbapenêmicos em CRAB (98 %; 95% IC: 0.91, 0.99; I² = 95 %), com bla OXA-23-like (91 %; 95 %; IC: 0,76; 0,97; I² = 97 %) ou bla OXA -51-like / ISAba1 (84 %; 95 % IC: 0.15, 0.99; I² = 98 %) genes, seguidos por metalo-ß-lactamases (MBL) (12 %, 95 % IC: 0,09, 0,15, I² = 99 %) e Klebsiella pneumoniae carbapenemase (KPC) (6 %, IC 95 %: 0,04; 0,08; I² = 87 %). Conclusão: Os estudos incluídos mostraram que a susceptibilidade à colistina (99 %) e tigeciclina (93 %) permanece alta e não foi afetada pela resistência aos carbapenêmicos.

Use of tigecycline at a teaching hospital / Uso da tigeciclina em hospital de ensino

INTRODUCTION: Tigecycline is an antimicrobial agent, approved for the treatment of complicated skin and soft tissue infections, hospital-acquired and community-acquired pneumonia, intra-abdominal infections and anaerobic or atypical infections. OBJECTIVE: To describe the use of tigecycline in a teaching hospital and to compare data from patients who had their prescriptions audited by the hospital infection committee with those who did not have audited prescriptions. METHODS: Retrospective observational cohort study conducted at a teaching hospital from April 2012 to March 2014 including patients who received tigecycline. Demographic variables, comorbidities, microbiological findings, prescribed antibiotics and technical opinions issued by the Hospital Infection Control Service were collected. RESULTS: 71 patients were included, aged between 13 and 92 years, 63.4% were male and 56.3% were non-white. Tigecycline was the first antimicrobial choice in 19.7% (14/71) of the cases, while the use associated with other antibiotics was observed in 66.2% (45/71) of the prescriptions. mainly with meropenem (28.9%). Empirical use was performed in 69.0% of cases, after culture and the antibiogram in 31.0% and off label use in 81.7%. The microorganisms frequently identified by the culture tests were Enterococcus faecalis (17.6%), Pseudomonas aeruginosa (14.7%) and Klebsiella penumoniae (11.8%). CONCLUSION: The study demonstrated that empirical and off label use is common in clinical practice and few prescriptions were guided by the results of the culture and the antibiogram, demonstrating the need for prescribers to evaluate the benefits/ risks of using this antibiotic, risk of resistance, adverse effects and drug interactions, in addition to cost.

INTRODUÇÃO: A tigeciclina é agente antimicrobiano, aprovada para o tratamento de infecções complicadas na pele e tecidos moles, pneumonia hospitalar e adquirida na comunidade, infecções intra-abdominal e infecções anaeróbias ou atípicas. OBJETIVO: Descrever o uso da tigeciclina em hospital de ensino e comparar dados de pacientes que tiveram suas prescrições auditadas pela comissão de infecção hospitalar com os que não tiveram prescrições auditadas. MÉTODOS: Estudo de coorte retrospectivo observacional realizado em hospital de ensino de abril de 2012 a março de 2014 incluindo pacientes que receberam tigeciclina. Foram coletadas variáveis ​​demográficas, comorbidades, achados microbiológicos, antibióticos prescritos e pareceres técnicos emitidos pelo Serviço de Controle de Infecção Hospitalar. RESULTADOS: Foram incluídos 71 pacientes, com idade entre 13 e 92 anos, 63,4% eram do sexo masculino e 56,3% eram não brancos. A tigeciclina foi primeira escolha antimicrobiana em 19,7% (14/71) dos casos, enquanto o uso associado a outros antibióticos foi observado em 66,2% (45/71) das prescrições. principalmente com meropenem (28,9%). O uso empírico foi realizado em 69,0% dos casos, após cultura e o antibiograma em 31,0% e o uso off label em 81,7%. Os microrganismos frequentemente identificados pelos testes de cultura foram Enterococcus faecalis (17,6%), Pseudomonas aeruginosa (14,7%) e Klebsiella penumoniae (11,8%). CONCLUSÃO: O estudo demonstrou que o uso empírico e off label é comum na prática clínica e poucas prescrições foram orientadas pelos resultados da cultura e do antibiograma, demonstrando necessidade de prescritores avaliarem os benefícios/riscos do uso desse antibiótico, risco de resistência, efeitos adversos e interações medicamentosas, além do custo.

Tigeciclina intraventricular como tratamiento de ventriculitis por Chryseobacterium indologenes multirresistente. A propósito de un caso pediátrico / Intraventricular tigecycline as a treatment for multidrug-resistant Chryseobacterium indologenes ventriculitis. About a pediatric case

Resumen La ventriculitis por Chryseobacterium indologenes puede ser un reto terapéutico importante, sobre todo cuando el germen adquiere resistencia intra tratamiento a los antimicrobianos habituales. La tigeciclina intraventricular podría ser una excelente opción en estos casos. Se presenta el caso de una escolar que recibió tratamiento intraventricular con tigeciclina, ante la ausencia de alternativas terapéuticas, con suceso exitoso.

Summary Ventriculitis due to Chryseobacterium indologenes can be a major therapeutic challenge, especially when the germ acquires intra-treatment resistance to common antimicrobials. Intraventricular tigecycline could be an excellent option in these cases. We present a schoolgirl`s case who received successfully intraventricular treatment with tigecycline.

Clinical efficacy of polymyxin B in combination with tigecycline in pneumonia caused by pan-drug resistant Klebsiella pneumoniae / 国际生物医学工程杂志

Objective:To investigate the clinical efficacy of injectable polymyxin B combined with tigecycline in pneumonia caused by pan-drug resistant Klebsiella pneumonia (PDR-KP). Methods:The retrospective analysis utilized clinical data of 71 patients with PDR-KP admitted to the Neurointensive Care Unit of Beijing Chaoyang Integrative Medicine Emergency Medical Center between September 2018 and August 2021. All patients received injectable polymyxin B combined with tigecycline. The response rate, bacterial clearance rate, and safety of this therapeutic option were evaluated according to the clinical symptoms and biochemical parameters before treatment (baseline), 7 days after the treatment, and at the end of the treatment.Results:The treatment time of 71 patients ranged from 8 to 14 days, with an average of 11 days. The symptoms, signs, laboratory tests, and chest CT findings of most patients significantly improved after the treatment using polymyxin B combined with tigecycline. On the 7th day after the treatment, 37 patients were clinically effective, with a total effective rate of 52.1%(37/71); 41 patients obtained bacteriological clearance, with a bacterial clearance rate of 57.7%(41/71). At the end of treatment, 51 patients were clinically effective, with a total effective rate of 71.8%(51/71); 56 patients obtained bacteriological clearance, with a bacterial clearance rate of 78.9%(56/71). Compared with the results on the 7th day after the treatment, the total effective rate ( χ2=5.86, P=0.016) and bacterial clearance rate ( χ2=7.32, P=0.007) of patients at the end of treatment were significantly increased. Skin pigmentation occurred in 39.4%(28/71) of patients during the treatment. Conclusions:Polymyxin B combined with tigecycline can be tried as a treatment option for pneumonia caused by PDR-KP, but more reliable clinical evidence is still needed.

In vitro antibacterial effects of imipenem combined with conventional antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae / 中国基层医药

Objective:To investigate the in vitro antibacterial effects of imipenem combined with common antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae (CRKP) targeting bla KPC-2 gene. Methods:Six strains of unrepeated bla KPC-2 type confirmed by polymerase chain reaction and DNA sequence were isolated in Yueqing People's Hospital, China between January 2018 and January 2019 were included in this study. The susceptibility rate of imipenem against nine conventionally used antibiotics was determined. The sensitivity test of imipenem combined with eight antibiotics was performed with the checkerboard method. Fractional inhibitory concentration was calculated to assess the efficacy of imipenem combined with common antibiotics. The in vitro treatment time-antibacterial effect curve was drawn to evaluate the antibacterial effects. Results:The resistance rate of six strains of bla KPC-2 type was 100.00% (6/6) for imipenem, meropenem, ceftazidime, ciprofloxacin, rifampicin and cefotaxime, and it was 66.67% (4/6) for minocycline and clavulanic acid and 33.33% (2/6) for tigecycline. Imipenem combined with tigecycline had a better antibacterial effect and exhibited a synergistic effect on four strains of bla KPC-2 type CRKP and an additive effect on two strains of Bla KPC-2 type CRKP. The curve of time for in vitro treatment of KPN2 with imipenem combined with tigecycline against bactericidal effect revealed that the antibacterial rate of imipenem at the 1/2 minimum inhibitory concentration combined with tigecycline at the 1/4 minimum inhibitory concentration was > 95% at (t+2) and the antibacterial effect could maintain (t+10) hours to (t+12) hours. The antibacterial rate of imipenem combined with tigecycline against strain 002 was gradually decreased with time, and the growth curve of strain 002 rised gradually. Conclusion:In vitro drug sensitivity test revealed that imipenem combined with tigecycline exhibits a good synergistic effect on bla KPC-2 type CRKP. Findings from this study provide a reference for clinical treatment of bla KPC-2 type CRKP.

Effect of donor-derived infection on clinical prognosis of kidney transplant recipients / 器官移植

Objective To evaluate the effect of donor-derived infection (DDI) on clinical prognosis of kidney transplant recipients. Methods Clinical data of 82 donors from donation after citizen's death and 148 kidney transplant recipients were retrospectively analyzed. According to the culture results of the lavage fluid of donor kidney, all recipients were divided into the lavage fluid culture of donor kidney positive group (positive group, n=92) and lavage fluid culture of donor kidney negative group (negative group, n=56). All recipients were assigned into the DDI group (n=19) and non-DDI group (n=129) according to whether they developed DDI or not. The distribution and composition ratio of positive strains in the lavage fluid of donor kidney were analyzed. The incidence of postoperative infection and other complications was assessed in the recipients. Perioperative conditions of the recipients were statistically compared between the DDI and non-DDI groups. The treatment efficacy and clinical prognosis of DDI recipients were evaluated. Results Among 148 recipients, 92 obtained positive culture results in the lavage fluid of donor kidney. A total of 131 pathogenic strains were isolated, including 41.2% (54/131) of Gram-positive cocci, 48.9% (64/131) of Gram-negative bacilli and 9.9%(13/131) of fungi. Among 148 recipients, 52 cases were infected. And 45% (41/92) and 20% (11/56) of the recipients were infected in the positive and negative group, respectively. Statistical significance was noted between two groups (P=0.002). Surgical site was the most common infection site in 52 infected recipients, followed by the urinary system. Nineteen recipients developed DDI with an incidence rate of 12.8% and fatality of 16%. Compared with the non-DDI recipients, DDI recipients had significantly higher graft loss rate and fatality, and longer postoperative hospital stay (all P < 0.05). Eight cases presented with carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, after treatment with tigecycline and/or polymyxin and carbapenems, 3 cases died, and 3 underwent kidney graft resection. In the other 8 recipients with CRKP infection, 2 cases were treated with ceftazidime-avibactam (CAZ-AVI) alone, 3 treated with CAZ-AVI combined with carbapenems, and 3 initially treated with tigecycline combined with carbapenems followed by CAZ-AVI for salvage treatment. After corresponding treatment, the recipients achieved long-term survival. Conclusions DDI may lead to severe complications, while early specific antibacterial treatment plays a positive role.

Population pharmacokinetics/pharmacodynamics of tigecycline in the treatment of different infectious diseases / 中国临床药理学与治疗学

AIM: To provide reference for the clinical application of tigecycline and subsequent population pharmacokinetic-pharmacodynamics study in the future. METHODS: The Chinese and English keywords of "Tigecycline", "population pharmacokinetics", "population pharmacokinetic model", "pharmacodynamics" or "Tigecycline" pharmacokinetics "were used to search the relevant references published from the time of self-establishment to June 1, 2021 in PubMed, China Knowledge Infrastructure, Wanfang and other databases. The research progress of population pharmacokinetics and pharmacodynamics of tigecycline was reviewed. RESULTS & CONCLUSION: A total of 73 relevant references were retrieved, including 8 tigecycline PPK studies and 7 tigecycline PK/PD studies. At present, tigecycline PPK models had been established in patients with complex intra-abdominal infections, skin and skin and soft tissue infections, community-acquired pneumonia, nosocomial pneumonia, septic shock and other severe infections, including 8 two-compartment models. The main covariates affecting tigecycline plasma clearance were weight-related, liver function and renal function-related parameters. Body weight was also an important factor influencing the apparent volume of distribution. The effect of different disease types on the pharmacokinetics of tigecycline was different, and it needed to be considered and selected in combination with the specific circumstances of patients when formulating clinical dosing regimens. Pharmacodynamics studies should consider not only the type of disease, pathogens and patient factors themselves, but also the characteristics of atypical nonlinear plasma protein binding of tigecycline. In order to accurately understand the efficacy of different dose regimens, it was necessary to monitor the therapeutic drugs of tigecycline.

Anti-tumor activity of tigecycline: a review / 生物工程学报

Tigecycline is a novel glycylcycline antibacterial drug, which shows both antibiotic function and anti-tumor activity. This review summarizes the single and combined use of tigecycline for tumor treatment and the underpinning mechanisms. As an inhibitor for mitochondrial DNA translation, tigecycline affects the proliferation, migration, and invasion of tumor cells mainly through inhibiting mitochondrial protein synthesis and inducing mitochondrial dysfunction. Although the effect of tigecycline monotherapy is controversial, the efficacy of combined use of tigecycline is satisfactory. Therefore, it is important to explore the molecular mechanisms underpinning the anti-tumor activity of tigecycline, with the aim to use it as a cheap and effective new anti-tumor drug.

Uso compasional de tigeciclina intraventricular en pacientes con ventriculitis causada por Enterococcus faecium. Reporte de seis casos pediátricos / Compassional use of Intraventricular Tigecycline in ventriculitis caused by Enterococcus faecium. Six pediatric cases

Introducción: La Tigeciclina es un fármaco de uso restringido en pediatría. El uso de este antibiótico por vía intraventricular es una decisión de uso compasivo en casos de bacterias altamente resistentes, y para los casos en que no exista otra alternativa. Caso clínico: Se presenta seis casos de pacientes con diagnóstico de ventriculitis a Enterococcus faecium que recibieron tigeciclina intraventricular con evolución bacteriológica exitosa. Se discute las dosis utilizadas por vía endovenosa e intraventricular. Conclusiones: el uso de este antibiótico por vía intraventricular puede ser una alternativa exitosa en casos de gérmenes altamente resistentes y cuando no exista otra alternativa terapéutica.

Introduction: Tigecycline is a drug of restricted use in pediatrics. The use of this antibiotic intraventricularly is a decision of compassive use in cases of highly resistant bacteria, and in cases where there is no other alternative. Clinical case: We present six cases of patients with a diagnosis of ventriculitis caused by Enterococcus faecium, who received intraventricular tigecycline with successful microbiological evolution. The doses used intravenously and intraventricularly are discussed. Conclusions: the use of this antibiotic intraventricularly can be a successful alternative in cases of highly resistant germs, when there are not alternative options. Key words: ventriculitis, Enterococcus faecium, tigecycline, intraventricula

Coagulase-negative staphylococci: a 20-year study on the antimicrobial resistance profile of blood culture isolates from a teaching hospital

ABSTRACT The increasing rates of nosocomial infection associated with coagulase-negative staphylococci (CoNS) were the rationale for this study, aiming to categorize oxacillin-resistant CoNS species recovered from blood culture specimens of inpatients at the UNESP Hospital das Clínicas in Botucatu, Brazil, over a 20-year period, and determine their sensitivity to other antimicrobial agents. The mecA gene was detected in 222 (74%) CoNS samples, and the four types of staphylococcal chromosomal cassette mec (SCCmec) were characterized in 19.4%, 3.6%, 54.5%, and 14.4% of specimens, respectively, for types I, II, III, and IV. Minimal inhibitory concentration (MIC) values to inhibit 50% (MIC50) and 90% (MIC90) of specimens were, respectively, 2 and >256 µL/mL for oxacillin, 1.5 and 2 µL/mL for vancomycin, 0.25 and 0.5 µL/mL for linezolid, 0.094 and 0.19 µL/mL for daptomycin, 0.19 and 0.5 µL/mL for quinupristin/dalfopristin, and 0.125 and 0.38 µL/mL for tigecycline. Resistance to oxacillin and tigecycline and intermediate resistance to quinupristin/dalfopristin were observed. Eight (2.7%) of all 300 CoNS specimens studied showed reduced susceptibility to vancomycin. Results from this study show high resistance rates of CoNS to antimicrobial agents, reflecting the necessity of using these drugs judiciously and controlling nosocomial dissemination of these pathogens.