RESUMO
BACKGROUND: Hepatic cyst infection is a potentially severe complication in cystic disease. Treatment demands effective antibiotic concentrations within the infected cyst. OBJECTIVES: The aim of this study was to use elective hepatic cyst drainage as a unique pharmacokinetic model to investigate whether cefazolin, a first-generation cephalosporin, is able to penetrate hepatic cysts. PATIENTS AND METHODS: Patients scheduled to undergo percutaneous aspiration sclerotherapy of a symptomatic non-infected, non-neoplastic hepatic cyst were eligible for this study. All participants received a single perioperative prophylactic dose of cefazolin (1000 mg, intravenously). We collected blood and cyst fluid samples to determine total and unbound cefazolin concentrations using HPLC. The primary outcome was hepatic cyst penetration, expressed as the ratio (%) of unbound concentration of cefazolin in cyst fluid to plasma (both in mg/L). RESULTS: We included eight patients [maleâ=â25%, median ageâ=â60 years (IQR 54-75), median estimated glomerular filtration rateâ=â97 mL/min/1.73 m(2) (IQR 67-102) and median serum albuminâ=â40 g/L (IQR 37-40)]. We detected low concentrations of unbound cefazolin in cyst fluid (≤1.0 mg/L). The median plasma unbound cefazolin peak level (immediately after cefazolin administration) was 36.6 mg/L (IQR 23.7-54.1) and the level at the time of cyst fluid aspiration was 16.1 mg/L (IQR 13.0-20.1). In total, the hepatic cyst penetration of free cefazolin was only 2.2% (IQR 0.7-5.2). CONCLUSIONS: We developed a study model to investigate the penetration of antibiotics into hepatic cysts. Cefazolin did not reach adequate intracystic concentrations. Future studies should explore alternatives.
Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Cefazolina/farmacocinética , Cistos/complicações , Hepatopatias/complicações , Escleroterapia , Idoso , Antibacterianos/administração & dosagem , Aspirações Psicológicas , Secreções Corporais/química , Cefazolina/administração & dosagem , Cromatografia Líquida de Alta Pressão , Cistos/cirurgia , Feminino , Humanos , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Plasma/químicaAssuntos
Ciprofloxacina/farmacocinética , Ciprofloxacina/uso terapêutico , Cistos/tratamento farmacológico , Cistos/microbiologia , Hepatopatias/tratamento farmacológico , Hepatopatias/microbiologia , Rim Policístico Autossômico Dominante/complicações , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Ciprofloxacina/farmacologia , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Cyst infection may occur in autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD). Antimicrobial agents often fail to control infection, leading to invasive action. We aimed to identify factors predicting escalation of care. METHODS: ADPKD and ADPLD patients were identified from local/national databases (2001-2013). Records were screened for patients meeting criteria for cyst infection (positive cyst aspirate and/or clinical findings). Factors that predict escalated care were identified with multivariate modified Poisson regression. RESULTS: We screened 1773 patients. A total of 77 patients with cyst infection (4.3%) were included for analysis (hepatic 36%; male 49%; age 54 ±; 13 years; ADPKD 95%; dialysis 9%, diabetes 18%, renal transplant 56%, eGFR [IQR 24-78] ml/min/1.73 m2 (excluding patients with a history of renal transplant or receiving dialysis)). A pathogen was identified in 71% of cases. Escherichia coli was the most common pathogen and accounted for 69% of cases. Initial treatment was limited to antibiotics in 87% of patients (n = 67), 40% included a fluoroquinolone. Ultimately, 48% of patients underwent some form of invasive action (escalation of care). Increasing white blood cell count (WBC) (RR 1.04 95%-CI 1.01-1.07, p = 0.008) was associated with escalating care, whereas an increase in time between transplant and infection (RR 0.92 95% CI 0.86-0.97, p = 0.005) and E. coli isolation (RR 0.55 95% CI 0.34-0.89, p = 0.02) were protective. CONCLUSION: High serum WBC, isolation of atypical pathogens and early infection after transplantation are factors that increase the risk of escalation of care in hepatic and renal cyst infection patients.
Assuntos
Antibacterianos/uso terapêutico , Cistos/complicações , Infecções por Escherichia coli/tratamento farmacológico , Hepatopatias/complicações , Rim Policístico Autossômico Dominante/complicações , Idoso , Cistos/genética , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/sangue , Infecções por Escherichia coli/cirurgia , Feminino , Humanos , Transplante de Rim , Contagem de Leucócitos , Hepatopatias/genética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Cyst infection is a severe complication of hepatic cystic disease. However, an evidence-based treatment strategy is not available. AIM: To assess the available treatment strategies and provide a treatment advice for de novo hepatic cyst infection. METHODS: We systematically searched PubMed (1948-2014), EMBASE (1974-2014), and the Cochrane Library (until 2014) for studies involving humans (≥18 years) treated for a hepatic cyst infection. We extracted data on patient characteristics, treatment and follow-up. RESULTS: We identified 41 articles; all were case series or case reports, implicating a high risk of bias. We included 54 hepatic cyst infection cases (male 39%; mean age 63 ± 12 years; diabetes 6%; dialysis 19%; transplant recipients 30%). Initial therapy consisted of antimicrobial (56%), percutaneous (31%) or surgical treatment (13%). We identified 42 antimicrobial regimens consisting of 23 different combinations. Most used antibiotic classes were quinolones (34%) and cephalosporins (34%). Antimicrobials failed in 70% of cases, eventually requiring percutaneous or surgical treatment in, respectively, 37% and 27%. Recurrent hepatic cyst infection was frequent (20%). Median time to recurrence was 8 weeks (IQR 3-24 weeks). In 46%, recurrence occurred in renal transplant recipients. Cyst infection related deaths occurred in 9%, of whom 40% were on dialysis. CONCLUSIONS: The literature shows that treatment of hepatic cyst infection is highly heterogeneous. We recommend first line treatment with oral ciprofloxacin. In case of failure, percutaneous cyst drainage needs to be considered.