RESUMO
PURPOSE: To date, there are three published guidelines discussing management of infected pancreatic necrosis (IPN) with conflicting recommendations. Specifically, The World Society of Emergency Surgery lists piperacillin-tazobactam as a treatment option in addition to meropenem and ciprofloxacin plus metronidazole. Piperacillin-tazobactam may serve as an effective carbapenem-sparing alternative. Although previous studies shed light on antimicrobial penetration data, there is a lack of clinical data comparing piperacillin-tazobactam to meropenem. The purpose of this study is to compare the efficacy of meropenem and piperacillin-tazobactam for the treatment of IPN. METHODS: This was a multicenter, retrospective cohort study conducted across three institutions. Patients with IPN who received either meropenem or piperacillin-tazobactam from January 2015 to December 2020 were included. The primary composite outcome was the incidence of 90-day clinical failure, which encompassed 90-day all-cause mortality and 90-day intra-abdominal infection recurrence. Secondary outcomes included length of hospital stay, antimicrobial duration of therapy, and the need for surgical intervention. RESULTS: We identified 229 patients with IPN that received either meropenem or piperacillin-tazobactam during hospital admission. After screening, 63 patients were included in the study. Incidence of 90-day clinical failure was observed in 33 % of the meropenem group and 50 % in the piperacillin-tazobactam group (OR, 1.98; 95 % CI 0.57 to 7.01, p = 0.259). The meropenem group had a lower incidence of 90-day infection recurrence in the piperacillin-tazobactam group (56 % vs 29 %, p = 0.047). CONCLUSIONS: Piperacillin-tazobactam may be an efficacious carbapenem-sparing treatment alternative for infected pancreatic necrosis.
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Antibacterianos , Meropeném , Combinação Piperacilina e Tazobactam , Humanos , Meropeném/uso terapêutico , Meropeném/administração & dosagem , Combinação Piperacilina e Tazobactam/uso terapêutico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Idoso , Pancreatite Necrosante Aguda/tratamento farmacológico , Adulto , Resultado do TratamentoRESUMO
BACKGROUNDS: The effectiveness of procalcitonin-based algorithms in guiding antibiotic usage for febrile acute necrotizing pancreatitis (ANP) remains controversial. Metagenomic next-generation sequencing (mNGS) has been applied to diagnose infectious diseases. The authors aimed to evaluate the effectiveness of blood mNGS in guiding antibiotic stewardship for febrile ANP. MATERIALS AND METHODS: The prospective multicenter clinical trial was conducted at seven hospitals in China. Blood samples were collected during fever (T ≥38.5°C) from ANP patients. The effectiveness of blood mNGS, procalcitonin, and blood culture in diagnosing pancreatic infection was evaluated and compared. Additionally, the real-world utilization of antibiotics and the potential mNGS-guided antimicrobial strategy in febrile ANP were also analyzed. RESULTS: From May 2023 to October 2023, a total of 78 patients with febrile ANP were enrolled and 30 patients (38.5%) were confirmed infected pancreatic necrosis (IPN). Compared with procalcitonin and blood culture, mNGS showed a significantly higher sensitivity rate (86.7% vs. 56.7% vs. 26.7%, P <0.001). Moreover, mNGS outperformed procalcitonin (89.5 vs. 61.4%, P <0.01) and blood culture (89.5 vs. 69.0%, P <0.01) in terms of negative predictive value. Blood mNGS exhibited the highest accuracy (85.7%) in diagnosing IPN and sterile pancreatic necrosis, significantly superior to both procalcitonin (65.7%) and blood culture (61.4%). In the multivariate analysis, positive blood mNGS (OR=60.2, P <0.001) and lower fibrinogen level (OR=2.0, P <0.05) were identified as independent predictors associated with IPN, whereas procalcitonin was not associated with IPN, but with increased mortality (Odds ratio=11.7, P =0.006). Overall, the rate of correct use of antibiotics in the cohort was only 18.6% (13/70) and would be improved to 81.4% (57/70) if adjusted according to the mNGS results. CONCLUSION: Blood mNGS represents important progress in the early diagnosis of IPN, with particular importance in guiding antibiotic usage for patients with febrile ANP.
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Antibacterianos , Febre , Sequenciamento de Nucleotídeos em Larga Escala , Pancreatite Necrosante Aguda , Pró-Calcitonina , Humanos , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/diagnóstico , Pró-Calcitonina/sangue , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Febre/tratamento farmacológico , Febre/diagnóstico , Febre/microbiologia , Adulto , China , Metagenômica , Idoso , Gestão de Antimicrobianos , Biomarcadores/sangueRESUMO
INTRODUCTION: Acute necrotizing pancreatitis (ANP) mortality increases when pancreatic necrosis is infected (IPN). Current treatment of IPN relies on prolonged antibiotic therapies associated with a step-up strategy of drainage. The objective of this study was to analyze IPN treatment outcomes in two referral centers in France. METHODS: Data of consecutive patients with documented IPN hospitalized in two expert centers in France between 2014 and 2019 were retrospectively reviewed. The composite primary outcome was the proportion of unsuccessful management outcome, defined as new emergency drainage to treat sepsis with organ failure, an unplanned new antibiotic course, an unplanned prolongation of antibiotic course and/or death by septic shock, within three months following the diagnosis of ANP. RESULTS: All in all, 187 patients (138 males; 74.0%), with documented IPN were included. The most frequently identified microorganism was Escherichia coli (26.2%). Ninety-eight patients (52.4%) were admitted to an intensive care unit or resuscitation ward within the first two days of ANP care. Overall, 126 patients (67.4%) endured an unsuccessful outcome: new emergency drainage to treat acute sepsis (62.0%), unplanned new antibiotic course (47.1%), unplanned prolongation of antibiotic course (44.9%) and/or death by septic shock complicating IPN (8.0%). CONCLUSION: The unfavorable evolution in two thirds of patients shows that determination of optimal drainage timing and choice of antibiotic therapy remain major challenges in 2024.
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Pancreatite Necrosante Aguda , Sepse , Choque Séptico , Masculino , Humanos , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/epidemiologia , Pancreatite Necrosante Aguda/complicações , Estudos Retrospectivos , Choque Séptico/tratamento farmacológico , Choque Séptico/epidemiologia , Choque Séptico/complicações , Resultado do Tratamento , Antibacterianos/uso terapêutico , Sepse/complicações , Sepse/tratamento farmacológicoRESUMO
BACKGROUND: Early systemic anticoagulation (SAC) is a common practice in acute necrotizing pancreatitis (ANP), and its impact on in-hospital clinical outcomes had been assessed. However, whether it affects long-term outcomes is unknown. This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients. METHODS: During January 2013 and December 2018, ANP patients admitted within 7 days from the onset of abdominal pain were screened. The primary outcome was 90-day readmission after discharge. Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission. RESULTS: A total of 241 ANP patients were enrolled, of whom 143 received early SAC during their hospitalization and 98 did not. Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis (SVT) [risk ratio (RR) = 0.40, 95% CI: 0.26-0.60, P < 0.01] and lower 90-day readmission with an RR of 0.61 (95% CI: 0.41-0.91, P = 0.02) than those who did not. For the quality of life, patients who received early SAC had a significantly higher score in the subscale of vitality (P = 0.03) while the other subscales were all comparable between the two groups. Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57 (95% CI: 0.34-0.96, P = 0.04). Mediation analysis showed that SVT mediated 37.0% of the early SAC-90-day readmission causality. CONCLUSIONS: The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients, and reduced SVT incidence might be the primary contributor.
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Pancreatite Necrosante Aguda , Trombose Venosa , Humanos , Readmissão do Paciente , Estudos Retrospectivos , Pancreatite Necrosante Aguda/diagnóstico , Pancreatite Necrosante Aguda/tratamento farmacológico , Qualidade de Vida , Fatores de Risco , Trombose Venosa/tratamento farmacológico , Anticoagulantes/efeitos adversosRESUMO
Bile acids are altered and associated with prognosis in patients with acute pancreatitis (AP). Here, we conduct targeted metabolomic analyses to detect bile acids changes in patients during the acute (n = 326) and the recovery (n = 133) phases of AP, as well as in healthy controls (n = 60). Chenodeoxycholic acid (CDCA) decreases in the acute phase, increases in the recovery phase, and is associated with pancreatic necrosis. CDCA and its derivative obeticholic acid exhibit a protective effect against acinar cell injury in vitro and pancreatic necrosis in murine models, and RNA sequencing reveals that the oxidative phosphorylation pathway is mainly involved. Moreover, we find that overexpression of farnesoid X receptor (FXR, CDCA receptor) inhibits pancreatic necrosis, and interfering expression of FXR exhibits an opposite phenotype in mice. Our results possibly suggest that targeting CDCA is a potential strategy for the treatment of acinar cell necrosis in AP, but further verification is needed.
Assuntos
Ácidos e Sais Biliares , Pancreatite Necrosante Aguda , Humanos , Camundongos , Animais , Pancreatite Necrosante Aguda/tratamento farmacológico , Doença Aguda , Receptores Citoplasmáticos e Nucleares , Ácido Quenodesoxicólico/farmacologia , Ácido Quenodesoxicólico/uso terapêuticoAssuntos
Carbapenêmicos , Pancreatite Necrosante Aguda , Humanos , Carbapenêmicos/uso terapêutico , Pancreatite Necrosante Aguda/tratamento farmacológico , Antibacterianos/uso terapêutico , Proteínas de Bactérias , Estudos Prospectivos , Combinação de Medicamentos , Testes de Sensibilidade Microbiana , CeftazidimaRESUMO
INTRODUCTION: In 1994, Claudio Bassi reported a case of medical treatment for infected pancreatic necrosis (IPN); then since 1996 numerous articles of case series were published with treatment only with antibiotics with good outcomes. OBJECTIVES: To present our experience in the management of patients with IPN with antibiotics (without drainage). METHODS: We retrospectively reviewed cases with a diagnosis of IPN from January 2018 to October 2020, focusing on those cases that were treated conservatively (hydro-electrolyte, nutritional support and antibiotics). The diagnosis was made by observing gas in the retroperitoneum by CT or by clinical deterioration of the patient with pancreatic necrosis without another focus. Fine needle aspiration was not performed. RESULTS: We identified 25 patients with a diagnosis of IPN; eleven were treated conservatively. According to Atlanta, modified in 2012, 3 were classified severely and the rest moderately severe. All received antibiotics for at least 3 weeks. None required parenteral nutrition. The mean hospital stay was 38 days. Three patients were readmitted. 8 underwent cholecystectomy after having resolved the condition; the rest were already cholecystectomized. There were no deaths in this series. CONCLUSIONS: IPN can be treated conservatively without drainage with good results in selected cases.
Introducción: En 1994, Claudio Bassi relató un caso de tratamiento médico de la necrosis pancreática infectada (NPI); luego desde 1996 se publicaron numerosos artículos de serie de casos con tratamiento solo con antibióticos con buenos resultados. OBJETIVOS: Presentar nuestra experiencia en el manejo de la necrosis pancreática infectada con antibióticos (sin drenaje). Métodos: Revisamos retrospectivamente los pacientes con diagnóstico de NPI desde enero de 2018 a octubre del 2020, enfocándonos en aquellos casos que se trataron de forma conservadora (soporte hidroelectrolítico, nutricional y antibióticos). El diagnóstico se realizó observando gas en el retroperitoneo por TC asociado o no a deterioro clínico del paciente con necrosis pancreática sin otro foco. No se realizó punción aspiración con aguja fina (PAAF). RESULTADOS: Identificamos 25 pacientes con diagnóstico de NPI. Once fueron tratados de forma conservadora. Según la clasificación de Atlanta, modificada en 2012, 3 casos fueron clasificados de forma grave y el resto moderadamente grave. Todos recibieron antibióticos al menos durante 3 semanas. Ninguno requirió nutrición parenteral. El promedio de estancia hospitalaria fue de 38 días. Tres pacientes fueron readmitidos. A 8 se les realizó colecistectomía luego de haber resuelto el cuadro; los restantes ya estaban colecistectomizados. No hubo muertes en esta serie. CONCLUSIONES: La NPI puede ser tratada de forma conservadora sin drenaje con buenos resultados en casos seleccionados.
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Infecções Intra-Abdominais , Pancreatite Necrosante Aguda , Humanos , Pancreatite Necrosante Aguda/diagnóstico por imagem , Pancreatite Necrosante Aguda/tratamento farmacológico , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Drenagem/métodos , Resultado do TratamentoRESUMO
Mucin-2 (MUC2) secreted by goblet cells participates in the intestinal barrier, but its mechanism in acute necrotizing pancreatitis (ANP) remains unclear. In acute pancreatitis (AP) patients, the functions of goblet cells (MUC2, FCGBP, CLCA1, and TFF3) decreased, and MUC2 was negatively correlated with AP severity. ANP rats treated with pilocarpine (PILO) (PILO+ANP rats) to deplete MUC2 showed more serious pancreatic and colonic injuries, goblet cell dysfunction, gut dysbiosis, and bacterial translocation than those of ANP rats. GC-MS analysis of feces showed that PILO+ANP rats had lower levels of butyric acid, isobutyric acid, isovaleric acid, and hexanoic acid than those of ANP rats. The expression of MUC2 was associated with colonic injury and gut dysbiosis. All these phenomena could be relieved, and goblet cell functions were also partially reversed by MUC2 supplementation in ANP rats. TNF-α-treated colonoids had exacerbated goblet cell dysfunction. MUC2 expression was negatively correlated with the levels of pro-inflammatory cytokines (IL-1ß and IL-6) (p < .05) and positively related to the expression of tight junction proteins (Claudin 1, Occludin, and ZO1) (p < .05). Downregulating MUC2 by siRNA increased the levels of the pro-inflammatory cytokines in colonoids. MUC2 might maintain intestinal homeostasis to alleviate ANP.
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Pancreatite Necrosante Aguda , Ratos , Animais , Mucina-2/genética , Mucina-2/metabolismo , Pancreatite Necrosante Aguda/induzido quimicamente , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/metabolismo , Disbiose/metabolismo , Doença Aguda , Citocinas/metabolismo , Homeostase , Mucosa Intestinal/metabolismoRESUMO
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 , Pancreatite Necrosante Aguda , Adulto , Humanos , Antibacterianos/efeitos adversos , Tigeciclina/efeitos adversos , Estudos Retrospectivos , Estudos de Casos e Controles , Centros de Atenção Terciária , Fatores de Risco , Pancreatite Necrosante Aguda/induzido quimicamente , Pancreatite Necrosante Aguda/tratamento farmacológicoRESUMO
BACKGROUND: Acute pancreatitis (AP) associated with the modulation of TNF-α-AMPK axis in the presence and absence of vitamin E has not been investigated before. MATERIAL AND METHODS: Rats were either injected with L-arginine (2.5 gm/kg) before being sacrificed after 48 h or were pre-treated with vitamin E (60 mg/kg) and continued receiving vitamin E until the end of the experiment. RESULTS: AP was developed as demonstrated by infiltration of inflammatory cells and profound pancreas tissue damage, which were substantially protected by vitamin E. In addition, L-arginine injections significantly (p < .0001) increased the expression of TNF-α mRNA and protein, and decreased phospho-AMPK and IL-10 mRNA and protein that was significantly (p < .0001) protected by vitamin E. Furthermore, vitamin E inhibited L-arginine-induced blood levels of LDH, amylase, and myeloperoxidase. CONCLUSIONS: L-arginine-induced acute pancreatitis modulates TNF-α-AMPK axis, IL-10 and other AP biomarkers, which is protected by vitamin E; thus, may offer therapeutic potential in humans.
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Pancreatite Necrosante Aguda , Humanos , Ratos , Animais , Pancreatite Necrosante Aguda/induzido quimicamente , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-10/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Vitamina E/farmacologia , Doença Aguda , Pâncreas/metabolismo , ArgininaRESUMO
Opioids are widely used for the pain management of acute pancreatitis (AP), but their impact on disease progression is unclear. Therefore, our aim was to study the effects of clinically relevant opioids on the severity of experimental AP. Various doses of fentanyl, morphine, or buprenorphine were administered as pre- and/or post-treatments in rats. Necrotizing AP was induced by the intraperitoneal injection of L-ornithine-HCl or intra-ductal injection of Na-taurocholate, while intraperitoneal caerulein administration caused edematous AP. Disease severity was determined by laboratory and histological measurements. Mu opioid receptor (MOR) expression and function was assessed in control and AP animals. MOR was expressed in both the pancreas and brain. The pancreatic expression and function of MOR were reduced in AP. Fentanyl post-treatment reduced necrotizing AP severity, whereas pre-treatment exacerbated it. Fentanyl did not affect the outcome of edematous AP. Morphine decreased vacuolization in edematous AP, while buprenorphine pre-treatment increased pancreatic edema during AP. The overall effects of morphine on disease severity were negligible. In conclusion, the type, dosing, administration route, and timing of opioid treatment can influence the effects of opioids on AP severity. Fentanyl post-treatment proved to be beneficial in AP. Clinical studies are needed to determine which opioids are best in AP.
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Buprenorfina/farmacologia , Fentanila/farmacologia , Morfina/farmacologia , Pancreatite Necrosante Aguda/patologia , Receptores Opioides mu/metabolismo , Índice de Gravidade de Doença , Analgésicos Opioides/farmacologia , Animais , Feminino , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/metabolismo , Ratos , Ratos Wistar , Receptores Opioides mu/genéticaRESUMO
BACKGROUND: The effectiveness of prophylactic antibiotics in severe acute pancreatitis (SAP) remains a debatable issue. This meta-analysis aimed to determine the efficacy of prophylactic carbapenem antibiotics in SAP. METHODS: This meta-analysis of prophylactic carbapenem antibiotics for SAP was conducted in PubMed, EMBASE, Web of Science, MEDLINE, and Cochrane Library up to February 2021. The related bibliographies were manually searched. The primary outcomes involved infected pancreatic or peripancreatic necrosis, mortality, complications, infections, and organ failure. RESULTS: Seven articles comprised 5 randomized controlled trials and 2 retrospective observational studies, including 3,864 SAP participants. Prophylactic carbapenem antibiotics in SAP were associated with a statistically significant reduction in the incidence of infections (odds ratio [OR]: 0.27; p = 0.03) and complications (OR: 0.48; p = 0.009). Nevertheless, no statistically significant difference was demonstrated in the incidence of infected pancreatic or peripancreatic necrosis (OR: 0.74; p = 0.24), mortality (OR: 0.69; p = 0.17), extrapancreatic infection (OR: 0.64, p = 0.54), pulmonary infection (OR: 1.23; p = 0.69), blood infection (OR: 0.60; p = 0.35), urinary tract infection (OR: 0.97; p = 0.97), pancreatic pseudocyst (OR: 0.59; p = 0.28), fluid collection (OR: 0.91; p = 0.76), organ failure (OR: 0.63; p = 0.19), acute respiratory distress syndrome (OR: 0.80; p = 0.61), surgical intervention (OR: 0.97; p = 0.93), dialysis (OR: 2.34; p = 0.57), use of respirator or ventilator (OR: 1.90; p = 0.40), intensive care unit treatment (OR: 2.97; p = 0.18), and additional antibiotics (OR: 0.59; p = 0.28) between the experimental and control groups. CONCLUSIONS: It is not recommended to administer routine prophylactic carbapenem antibiotics in SAP.
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Antibioticoprofilaxia , Pancreatite Necrosante Aguda , Doença Aguda , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Humanos , Necrose/complicações , Necrose/tratamento farmacológico , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Percutaneous catheter drainage (PCD's) are prone to blockage because of necrosum. To improve the efficacy of PCD, necrolytic agents have been used. The present study compared the use of Streptokinase with H2O2 in saline irrigation. MATERIALS AND METHODS: This is a single-center randomized pilot study (from July 2018 to Dec 2019). Patients with infected pancreatic necrosis not showing response to PCD and saline irrigation were included in the study. Patients received either Streptokinase (Streptokinase group 50,000 IU in 100 ml normal saline) or 3% H2O2 (3% H2O2 in 100 ml normal saline in 1:10 dilution). Primary endpoints were the need for surgery and mortality while secondary endpoints were hospital stay and complications attributable to necrolytic agents. RESULTS: There were 30 patients in the study, 15 in each arm. Organ failure was seen in 23 (76.6%), single organ failure was present in 11 (47%), and multi-organ failure in 12 (53%). Bleeding complications (20% in H2O2 vs 6.6% in Streptokinase), need for surgery (73% in H2O2 vs 33.3% in Streptokinase) and mortality (60% in H2O2 vs 33% in Streptokinase) were higher in H2O2 group but the difference was not significant statistically. Post-irrigation hospital stay was lesser in the Streptokinase group compared to H2O2 group but the difference did not reach statistical significance (14.1 ± 7.7 vs 19.2 ± 11.7, p = 0.09) CONCLUSIONS: Streptokinase irrigation led to a trend for reduced need for necrosectomy and mortality. H2O2 group had more bleeding complications. Post-irrigation hospital stay was lesser in Streptokinase group.