Characteristics of Gram-positive cocci infection and the therapeutic effect after liver transplantation / 中南大学学报(医学版)

OBJECTIVES@#Gram-positive cocci is the main pathogen responsible for early infection after liver transplantation (LT), posing a huge threat to the prognosis of liver transplant recipients. This study aims to analyze the distribution and drug resistance of Gram-positive cocci, the risk factors for infections and efficacy of antibiotics within 2 months after LT, and to guide the prevention and treatment of these infections.@*METHODS@#In this study, data of pathogenic bacteria distribution, drug resistance and therapeutic efficacy were collected from 39 Gram-positive cocci infections among 256 patients who received liver transplantation from donation after citizens' death in the Third Xiangya Hospital of Central South University from January 2019 to July 2022, and risk factors for Gram-positive cocci infection were analyzed.@*RESULTS@#Enterococcus faecium was the dominant pathogenic bacteria (33/51, 64.7%), followed by Enterococcus faecalis (11/51, 21.6%). The most common sites of infection were abdominal cavity/biliary tract (13/256, 5.1%) and urinary tract (10/256, 3.9%). Fifty (98%) of the 51 Gram-positive cocci infections occurred within 1 month after LT. The most sensitive drugs to Gram-positive cocci were teicoplanin, tigecycline, linezolid and vancomycin. Vancomycin was not used in all patients, considering its nephrotoxicity. Vancomycin was not administered to all patients in view of its nephrotoxicity.There was no significant difference between the efficacy of daptomycin and teicoplanin in the prevention of cocci infection (P>0.05). Univariate analysis indicated that preoperative Model for End-Stage Liver Disease (MELD) score >25 (P=0.005), intraoperative red blood cell infusion ≥12 U (P=0.013) and exposure to more than 2 intravenous antibiotics post-LT (P=0.003) were related to Gram-positive cocci infections. Multivariate logistic regression analysis revealed that preoperative MELD score >25 (OR=2.378, 95% CI 1.124 to 5.032, P=0.024) and intraoperative red blood cell transfusion ≥ 12 U (OR=2.757, 95% CI 1.227 to 6.195, P=0.014) were independent risk factors for Gram-positive cocci infections after LT. Postoperative Gram-positive cocci infections were reduced in LT recipients exposing to more than two intravenous antibiotics post-LT (OR=0.269, 95% CI 0.121 to 0.598, P=0.001).@*CONCLUSIONS@#Gram-positive cocci infections occurring early after liver transplantation were dominated by Enterococcus faecalis infections at the abdominal/biliary tract and urinary tract. Teicoplanin, tigecycline and linezolid were anti-cocci sensitive drugs. Daptomycin and teicoplanin were equally effective in preventing cocci infections due to Gram-positive cocci. Patients with high preoperative MELD score and massive intraoperative red blood cell transfusion were more likely to suffer Gram-positive cocci infection after surgery. Postoperative Gram-positive cocci infections were reduced in recipients exposing to more than two intravenous antibiotics post-LT.

Antibioticoterapia y nuevas terapias no farmacológicas en infecciones por clostridium diffici / Antibiotic therapy and new non-pharmacological therapies in clostridium diffici infections

Resumen:La infección por Clostridium difficile es la principal causa de diarrea infecciosa en pacientes hospitalizados. Los pacientes pueden ser portadores asintomáticos o presentar desde una diarrea leve a una colitis pseudomembranosa, megacolon tóxico, sepsis y muerte. El manejo de esta infección sigue presentando puntos de controversia, tanto en la elección del mejor método diagnóstico como en el tratamiento. En los casos en los cuales la infección por este agente fue confirmada la primera y más efectiva medida es suspender la antibioticoterapia que el paciente este recibiendo, en la medida de lo posible. El tratamiento se basa en tres agentes clásicos: metronidazol, vancomicina y teicoplanina con la más reciente adición de fidaxomicina y ridinilazol. Pacientes con presentación severa muchas veces requieren resolución quirúrgica además de las medidas de soporte y monitoreo. El objetivo de esta revisión es ofrecer información actualizada sobre la patogénesis y estrategias terapéuticas sobre el manejo de la infección por este patógeno.

Abstract:Clostridium difficile infection is the leading cause of hospital acquired diarrhea. The patients can be asymptomatic carriers or present a mild diarrhea, a pseudomembranous colitis, toxic megacolon, sepsis and death. There is controversy in this infection's including the best method of diagnosis and also regarding therapeutic regimen.In cases in which Clostridium infection is confirmed, the first and most effective measure is the withdrawal of any antibiotic treatment the patient is receiving, if possible. The antimicrobial treatment is based on three classic agents: metronidazole, vancomycin and teicoplanin, along with the recent addition of fidaxomicin and ridinilazol.Patients presenting serious symptoms, in addition to appropriate support and monitoring measures, may require surgical treatment. This review's aim is to provide an update on the pathogenesis, and therapeutic strategies on the management of this pathogen.

Meta-análise Cochrane: teicoplanina versus vancomicina para infecções suspeitas ou confirmadas / Cochrane meta-analysis: teicoplanin versus vancomycin for proven or suspected infection

Objective: To compare efficacy and safety of vancomycin versus teicoplanin in patients with proven or suspected infection. Methods: Data Sources: Cochrane Renal Group's Specialized Register, CENTRAL, MEDLINE, EMBASE, nephrology textbooks and review articles. Inclusion criteria: Randomized controlled trials in any language comparing teicoplanin to vancomycin for patients with proven or suspected infection. Data extraction: Two authors independently evaluated methodological quality and extracted data. Study investigators were contacted for unpublished information. A random effect model was used to estimate the pooled risk ratio (RR) with 95% confidence interval (CI). Results: A total of 24 studies (2,610 patients) were included. The drugs had similar rates of clinical cure (RR: 1.03; 95%CI: 0.98-1.08), microbiological cure (RR: 0.98; 95%CI: 0.93-1.03) and mortality (RR: 1.02; 95%CI: 0.79-1.30). Teicoplanin had lower rates of skin rash (RR: 0.57; 95%CI: 0.35-0.92), red man syndrome (RR: 0.21; 95%CI: 0.08-0.59) and total adverse events (RR: 0.73; 95%CI: 0.53-1.00). Teicoplanin reduced the risk of nephrotoxicity (RR: 0.66; 95%CI: 0.48-0.90). This effect was consistent for patients receiving aminoglycosides (RR: 0.51; 95%CI: 0.30-0.88) or having vancomycin doses corrected by serum levels (RR: 0.22; 95%CI: 0.10-0.52). There were no cases of acute kidney injury needing dialysis. Limitations: Studies lacked a standardized definition for nephrotoxicity. Conclusions: Teicoplanin and vancomycin are equally effective; however the incidence of nephrotoxicity and other adverse events was lower with teicoplanin. It may be reasonable to consider teicoplanin for patients at higher risk for acute kidney injury.

Objetivo: Comparar eficácia e toxicidade da teicoplanina e da vancomicina em pacientes com infecção suspeita ou confirmada. Métodos: Fontes de dados: Cochrane Renal Group's Specialized Register, CENTRAL, MEDLINE, EMBASE, livros de referência e artigos de revisão. Critérios de inclusão: Ensaios clínicos controlados randomizados em qualquer idioma, comparando teicoplanina e vancomicina em pacientes com infecção suspeita ou confirmada. Extração de dados: Dois autores avaliaram a qualidade metodológica dos estudos e extraíram os dados de forma independente. Tentou-se obter dados não publicados diretamente com os autores de cada trabalho. Usou-se um modelo de efeito aleatório para estimar a razão de risco (RR) combinada, com um intervalo de confiança (IC) de 95%. Resultados: Foram incluídos 24 estudos (2.610 pacientes). As drogas tiveram taxas semelhantes de cura clínica (RR: 1,03; IC95%: 0,98-1,08), cura microbiológica (RR: 0,98; IC95%: 0,93-1,03) e mortalidade (RR: 1,02; IC95%: 0,79-1,30). A teicoplanina apresentou menores incidências de rash cutâneo (RR: 0,57; IC95%: 0,35-0,92), síndrome do homem vermelho (RR: 0,21; IC95%: 0,08-0,59) e eventos adversos em geral (RR: 0,73; IC95%: 0,53-1,00). A teicoplanina reduziu o risco de nefrotoxicidade (RR: 0,66; IC95%: 0,48-0,90). Esse efeito foi consistente em todos os subgrupos, inclusive aqueles com pacientes recebendo aminoglicosídeos concomitantes (RR: 0,51; IC95%: 0,30-0,88) oucom dosagens de vancomicina corrigidas pelo nível sérico (RR: 0,22; IC95%: 0,10-0,52). Não foi encontrado nenhum caso de injúria renal que necessitasse de diálise. Limitações: Os estudos não seguiram uma definição padrão de nefrotoxicidade. Conclusões: Teicoplanina e vancomicina têm eficácia semelhante; no entanto, o risco de nefrotoxicidade e outros eventos adversos foi menor com teicoplanina. É razoável considerar o uso de teicoplanina para pacientes em risco de desenvolver injúria renal aguda.

Mecanismos de resistencia a gliocopéptidos en Staphylococcus aureus / Mechanisms of resistance to glycopeptides in Staphylococcus aureus

Los glicopéptidos (vancomicina y teicoplanina) constituyen una alternativa terapéutica en el tratamiento de infecciones severas por cepas de S. aureus resistentes a meticilina. Sin embargo, ya se han descrito dos mecanismos de resistencia en S. aureus: resistencia de bajo nivel, caracterizada por un engrosamiento anormal de la pared celular, presente en las cepas VISA y, resistencia de alto nivel mediada por el operón vanA, que provoca la sustitución de los residuos terminales D-ala-D-ala por D-ala-D-lac, disminuyendo su afinidad por el antibiótico. Esta revisión resume la historia de la aparición de la resistencia a glicopéptidos en S. aureus y considera los mecanismos que determinan la resistencia en estos organismos como base para comprender la necesidad y los potenciales roles de nuevos agentes de esta clase

Glycopeptides (vancomycin and teicoplanin) are an alternative therapeutic in the treatment of severe infections by methicillin-resistant S. aureus strains. However, two resistance mechanisms of S. aureus have already been described: low-level resistance, characterized by an abnormal thickening of the cellular wall, present in the VISA strains, and high-level resistance, mediated by the vanA operon, which causes the replacement of D-ala - D-ala terminal residues by D-ala-D-lac, decreasing its affinity for the antibiotic. This review summarizes the history of the emergence of glycopeptide resistance in S. aureus and considers the mechanisms that determine the resistance in these organisms as a background for understanding the need and potential roles of new agents of this kind

Cardiogenic shock due to citomegalovirus myocarditis: successful clinical treatment / Choque cardiogênico devido à miocardite por citomegalovírus: terapêutica clínica com sucesso

OBJECTIVE: Cytomegalovirus (CMV) systemic disease and myocarditis in healthy persons is infrequently reported in the literature, although in increasing numbers in recent years. The importance of the recognition of the syndrome that usually has an initial picture of a mononucleosis like infection in an otherwise healthy person, is the available therapeutic agent, ganciclovir, that can cure the infectious disease. METHODS: We analyzed the clinical result of pulsotherapy with steroids in a patient with CMV myocarditis after 7 days of etiological treatment, with ganciclovir, intravenous vasodilators, and the conventional treatment for congestive heart failure. RESULTS: The clinical condition of the patient improved accordingly to the better function of the left ventricle, and the ganciclovir was kept for 21 days, most of it in an out patient basis. The patient was dismissed from the hospital, with normal myocardial function. CONCLUSION: Potentially curable forms of myocarditis, like M pneumoniae and CMV, for example, can have an initial disproportionate aggression to the myocardium, by the acute inflammatory reaction, that can by itself make worse the damage to the LV function. In our opinion, the blockade of this process by pulsotherapy with steroids can help in the treatment of these patients. We understand that the different scenario of immunosuppressive treatments for the possible auto immunity of the more chronic forms of the presumably post viral cardiomyopathy has been in dispute in the literature, and has stolen the focus from the truly acute cases.

OBJETIVO: Doença sistêmica por citomegalovírus (CMV) com miocardite em pessoas saudáveis é raramente referida na literatura, apesar de em maior número em anos recentes. A importância do reconhecimento da síndrome, que usualmente tem um quadro inicial "mononucleosis like" em uma pessoa sadia é a disponibilidade do agente terapêutico ganciclovir, que pode curar a infecção. MÉTODOS: Nós analisamos o resultado da pulsoterapia com esteróides em um paciente com miocardite por CMV, após 7 dias de tratamento etiológico com ganciclovir, vasodilatadores intravenosos e o tratamento convencional para insuficiência cardíaca congestiva. RESULTADOS: A condição clínica do paciente melhorou com a melhor função do ventrículo esquerdo e o ganciclovir foi mantido por 21 dias após alta hospitalar.A função miocárdica retornou ao normal. CONCLUSÃO: Formas curáveis de miocardites como M pneumonia e CMV, por exemplo, podem ter uma agressão grave ao miocárdio por uma ação inflamatória que pode piorar a função cardíaca. Em nossa opinião, o bloqueio deste processo pela pulsoterapia com esteróides pode auxiliar no tratamento destes pacientes. Entendemos que existe um cenário diferente de tratamento com imunossupressores para possível agressão auto-imune das formas mais crônicas de cardiomiopatias dilatadas e isso está em disputa na literatura, talvez mudando o foco dos casos realmente agudos.

Antimicrobianos en Unidades de Cuidados Intensivos: uso empírico / Antimicrobial agents in Intensive Care Units: empirical use

Las infecciones son causa importante de mortalidad en las unidades de cuidados intensivos. Actualmente predominan en Chile las causadas por cocáceas Gram positivas (Staphylococcus aureus resistente a meticilina, Staphylococcus coagulasa negativa y Enterococcus resistente a vancomicina) y en segundo lugar bacilos Gram negativos multiresistentes (Klebsiella pneumoniae). Una indicación antimicrobiana tardía o errada eleva significativamente la letalidad de las infecciones en estas condiciones. La introducción de métodos automatizados de hemocultivos y de técnicas de rápida identificación microbiana permiten emplear antimicrobianos de amplio espectro en una indicación empírica inicial y efectuar rápidos ajustes terapéuticos adecuados a cada situación. Se revisan someramente las bondades y limitaciones de nuevos antimicrobianos potencialmente útiles en estas situaciones: cefepime, carbapenems, nuevas quinolonas, pristinamicina, teicoplanina y linezolid. La indicación de antimicrobianos debe fundamentarse en la epidemiología local de resistencia en las infecciones de origen nosocomial.

La teicoplanina en la profilaxis de infecciones quirúrgicas y endocarditis bacteriana / [Teicoplanin in the prophylaxis of surgical infections and bacterial endocarditis]

Antibiotic prophylaxis has become a standard of care in all surgical categories, since its impact in reducing the incidence of post-operative infections has now been well established. Antibiotic prophylaxis should target expected pathogens. Glycopeptide-based regimens have been considered a choice for surgical procedures, since Gram-positive bacteria are the pathogens most commonly isolated from wound infections. In orthopedics, cardiac, vascular and other clean surgical procedures, staphylococci (S. aureus and coagulase-negative staphylococci) are responsible for 70-90

of post-surgical infections. The isolation of methicillin-resistant strains has also risen to alarmingly high rates. This article focuses on the results of clinical trials on the efficacy of teicoplanin as prophylaxis in clean surgical procedures.

Nuevas modalidades terapéuticas en el uso de teicoplanina / [New therapeutic strategies with teicoplanin]

Teicoplanin is a glycopeptide antibiotic with similar spectrum to vancomycin. However, unlike this drug, teicoplanin can be administered by i.v. or i.m. route once daily thanks to its long half-life (88 to 182 hours). This pharmacokinetic characteristic is particularly interesting in infections that require extended antimicrobial therapy, where new therapeutic strategies may be considered. Long-term treatment with teicoplanin proved effective in the treatment of bone and joint infections due to methicillin-resistant staphylococci. Teicoplanin administered three times a week yields comparable clinical efficacy than daily administration with considerably improved cost-effectiveness. This aspect merits special attention, particularly when evaluating prolonged outpatient antibiotic therapy regimens. For synergic effects it is possible to associate teicoplanin with other antibiotics. Chronic suppressive antibiotic therapy with teicoplanin may be an alternative in carefully selected patients, particularly those carrying prosthetic devices.