trimethoprim--sulfamethoxazole-drug-combination and Liver-Cirrhosis

Bacterial infections are well described complications of cirrhosis that greatly increase mortality rates. Two factors play important roles in the development of bacterial infections in these patients: the severity of liver disease and gastrointestinal haemorrhage. The most common infections are spontaneous bacterial peritonitis, urinary tract infections, pneumonia and sepsis. Gram-negative and gram-positive bacteria are equal causative organisms. For primary prophylaxis, short-term antibiotic treatment (oral norfloxacin or ciprofloxacin) is indicated in cirrhotic patients (with or without ascites) admitted with gastrointestinal haemorrhage (variceal or non-variceal). Administration of norfloxacin is advisable for hospitalized patients with low ascitic protein even without gastrointestinal haemorrhage. The first choice in empirical treatment of spontaneous bacterial peritonitis is the iv. III. generation cephalosporin; which can be switched for a targeted antibiotic regime based on the result of the culture. The duration of therapy is 5-8 days. Amoxicillin/clavulanic acid and fluoroquinolones--patients not on prior quinolone prophylaxis--were shown to be as effective and safe as cefotaxime. In patients with evidence of improvement, iv. antibiotics can be switched safely to oral antibiotics after 2 days. In case of renal dysfunction, iv albumin should also be administered. Long-term antibiotic prophylaxis is recommended in patients who have recovered from an episode of spontaneous bacterial peritonitis (secondary prevention). For "selective intestinal decontamination", poorly absorbed oral norfloxacin is the preferred schedule. Oral ciprofloxacin or levofloxacin (added gram positive spectrum) all the more are reasonable alternatives. Trimethoprim/sulfamethoxazole is only for patients who are intolerant to quinolones. Prophylaxis is indefinite until disappearance of ascites, transplant or death. Long-term prophylaxis is currently not recommended for patients without previous spontaneous bacterial peritonitis episode, not even when refractory ascites or low ascites protein content is present.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ascites; Bacteremia; Bacterial Infections; Cefotaxime; Cephalosporins; Ciprofloxacin; Fluoroquinolones; Gastrointestinal Hemorrhage; Humans; Infusions, Intravenous; Liver Cirrhosis; Norfloxacin; Peritonitis; Pneumonia, Bacterial; Primary Prevention; Severity of Illness Index; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Bacterial infection is a major cause of mortality in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is a serious and common infection in patients with cirrhosis and ascites. Secondary prophylactic antibiotic therapy has been shown to improve outcomes after an episode of SBP but primary prophylaxis to prevent the first episode of SBP remains contentious. The aim of this trial is to assess whether primary antibiotic prophylaxis with co-trimoxazole improves overall survival compared to placebo in adults with cirrhosis and ascites.. The ASEPTIC trial is a multicentre, placebo-controlled, double-blinded, randomised controlled trial (RCT) in England, Scotland, and Wales. Patients aged 18 years and older with cirrhosis and ascites requiring diuretic treatment or paracentesis, and no current or previous episodes of SBP, are eligible, subject to exclusion criteria. The trial aims to recruit 432 patients from at least 30 sites. Patients will be randomised in a 1:1 ratio to receive either oral co-trimoxazole 960 mg or an identical placebo once daily for 18 months, with 6 monthly follow-up visits thereafter (with a maximum possible follow-up period of 48 months, and a minimum of 18 months). The primary outcome is overall survival. Secondary outcomes include the time to the first incidence of SBP, hospital admission rates, incidence of other infections (including Clostridium difficile) and antimicrobial resistance, patients' health-related quality of life, health and social care resource use, incidence of cirrhosis-related decompensation events, liver transplantation, and treatment-related serious adverse events.. This trial will investigate the efficacy, safety, and cost-effectiveness of co-trimoxazole for patients with liver cirrhosis and ascites to determine whether this strategy improves clinical outcomes. Given there are no treatments that improve survival in decompensated cirrhosis outside of liver transplant, if the trial has a positive outcome, we anticipate widespread adoption of primary antibiotic prophylaxis.. ClinicalTrials.gov NCT043955365 . Registered on 18 April 2020. Research ethical approval was granted by the Research Ethics Committee (South Central - Oxford B; REC 19/SC/0311) and the Medicines and Healthcare products Regulatory Agency (MHRA).

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Ascites; Bacterial Infections; Diuretics; Humans; Liver Cirrhosis; Multicenter Studies as Topic; Peritonitis; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

To prospectively compare norfloxacin (N) with trimethoprim-sulfamethoxazole (T-S) in preventing infection in cirrhotic patients.. Cirrhotic patients at high risk of spontaneous bacterial peritonitis (SBP) were recruited and assigned N (400 mg daily) or T-S (160/800 mg daily). Patients were followed up for 12 months. The primary end-point was the incidence of infection. Secondary end-points included the incidence of SBP, bacteremia, extraperitoneal infection requiring antibiotic treatment, liver transplantation, death, side effects and rate of resistance to N or T-S.. A total of 80 patients with a mean age of 53.0 ± 9.3 years were prescribed N (n = 40) or T-S (n = 40). Child-Pugh status, model for end-stage liver disease and risk factors for SBP were similar between the groups. There were 10 episodes of infections in the N group and 9 in the T-S group (P = 0.79). Two patients each in the N and T-S group developed SBP (P = 0.60). There was a difference in the rate of transplantation favoring N (P = 0.03) but not death. The number of adverse events for N (n = 7) and T-S (n = 10) were similar (P = 0.59), with T-S being associated with an increased risk of developing a definite or probable adverse event compared to N (22.5% vs 0%, P = 0.01).. This study failed to demonstrate a difference between N and T-S groups in their effects on preventing infection in patients with liver cirrhosis. T-S can be considered an alternative first-line therapy for infection prophylaxis.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Bacteremia; Bacterial Infections; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Norfloxacin; Peritonitis; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis and ascites.. A randomized controlled trial.. University-affiliated Veterans Affairs medical center.. 60 consecutive patients with cirrhosis and ascites.. Consecutive patients were randomly assigned to receive either no prophylaxis or trimethoprim-sulfamethoxazole, one double-strength tablet daily, five times a week (Monday through Friday). Patient entry was stratified by serum bilirubin (> 51 mumol/L [> 3 mg/dL]), ascitic fluid protein (< 1 g/dL), and serum creatinine (> 177 mumol/L [> 2 mg/dL]) levels to ensure that high-risk patients would be similarly distributed in the two groups. The median duration of follow-up for the study patients was 90 days.. Spontaneous bacterial peritonitis or spontaneous bacteremia as defined by objective criteria.. Spontaneous bacterial peritonitis or spontaneous bacteremia developed in 27% (8 of 30) of patients who did not receive prophylaxis compared with 3% (1 of 30) of patients receiving trimethoprim-sulfamethoxazole (P = 0.025). Overall, infections developed in 9 of 30 patients (30%) not receiving prophylaxis and in 1 of 30 patients (3%) receiving trimethoprim-sulfamethoxazole (P = 0.012). Death occurred in 6 of 30 patients (20%) who did not receive prophylaxis and in 2 of 30 patients (7%) who received trimethoprim-sulfamethoxazole (P = 0.15). Side effects--particularly, hematologic toxicity--could not be attributed to trimethoprim-sulfamethoxazole in any patient.. Trimethoprim-sulfamethoxazole was efficacious, safe, and cost-effective for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis.

Topics: Ascites; Bacteremia; Bacterial Infections; Cost-Benefit Analysis; Humans; Liver Cirrhosis; Peritonitis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The paper describes a patient who has developed Whipple's disease in the presence of infantile cerebral palsy and hepatitis B virus cirrhosis. After 5-year treatment with co-trimoxazole (480 mg b.i.d.), the clinical manifestations subsided and PAS-positive macrophages were no longer detectable in the small intestinal mucosal biopsy specimens. Subsequent worsening of the patient's condition was associated with the progression of liver cirrhosis.

Topics: Adult; Biopsy; Cerebral Palsy; Disease Progression; Hepatitis B; Humans; Liver Cirrhosis; Macrophages; Male; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Whipple Disease

Topics: Abdominal Cavity; Aged, 80 and over; Anti-Infective Agents; Ascites; Cefotaxime; Diagnosis, Differential; Diet, Sodium-Restricted; Diuretics; Edema; Humans; Inflammation; Liver Cirrhosis; Lower Extremity; Male; Norfloxacin; Paracentesis; Peritonitis; Spironolactone; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography

Toll-like receptors (TLRs) are critical to innate immune responses. TLR4 recognises Gram-negative bacteria, whilst TLR2 recognises Gram-positive. We examined TLR expression and function in cirrhosis, and whether this is affected by antibiotic therapy.. Sixty-four subjects were included (23 controls and 41 Child-Pugh C cirrhotic patients). Thirty patients were taking norfloxacin or trimethoprim-sulfamethoxazole as prophylaxis against bacterial peritonitis and 11 were not. In a second study, 8 patients were examined before and after commencement of antibiotics. Monocyte expression of TLR2 and 4 was determined by flow cytometry. Monocytes from the patients with paired samples were stimulated using TLR ligands and TNF-alpha production measured.. Patients not taking antibiotics had significantly decreased TLR4 expression compared with controls (0.74 vs. 1.0, p=0.009) and patients receiving antibiotics (0.74 vs. 0.98, p=0.02). There were no differences with regard to TLR2. In the patients with paired samples, TLR4 expression increased (0.74-1.49, p=0.002) following antibiotic use, whilst again, there was no change in TLR2 expression (0.99 vs. 0.92, p=0.20). TLR4-dependent TNF-alpha production increased following antibiotic use (1077 vs. 3620pg/mL, p<0.05), whilst TLR2-dependent production was unchanged.. TLR4 expression is decreased in patients with Child-Pugh C cirrhosis, but is restored by antibiotics targeting enteric Gram-negative bacteria. TLR4-dependent cytokine production also increases significantly following antibiotic therapy. This suggests that the high incidence of Gram-negative infection in cirrhotic patients is in part due to down-regulation of the TLR4-dependant immune response and that the efficacy of antibiotic prophylaxis is contributed to by modulation of innate immunity.

Topics: Adult; Aged; Anti-Bacterial Agents; Case-Control Studies; Female; Gram-Negative Bacterial Infections; Humans; Immunity, Innate; In Vitro Techniques; Leukocytes, Mononuclear; Liver Cirrhosis; Male; Middle Aged; Norfloxacin; Peritonitis; Toll-Like Receptor 2; Toll-Like Receptor 4; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Topics: Ampicillin; Anti-Bacterial Agents; Back Pain; Bacteremia; Diagnosis, Differential; Discitis; Haemophilus; Haemophilus Infections; Humans; Intervertebral Disc; Liver Cirrhosis; Magnetic Resonance Imaging; Male; Middle Aged; Osteomyelitis; Trimethoprim, Sulfamethoxazole Drug Combination

This case control study assessed risk factors and prognostic indicators of 350 episodes of bacterial pneumonia in 285 HIV-infected patients. On univariate analysis, intravenous drug abuse (i.v.DA; p < .001 versus controls), regular cigarette smoking (p < .001), cirrhosis (p = .04), and history of a previous episode of pneumonia (p = .04) were risk factors for community-acquired episodes of bacterial pneumonia, whereas length of hospitalization (p = .01) was a risk factor only for nosocomial bacterial pneumonia. The small amount of circulating T CD4+ cells (<100/ mm3) was a risk factor in both groups of pneumonia (p < .05). Stepwise logistic regression analysis revealed that i.v.DA in community-acquired episodes and low levels of circulating T CD4+ cells, both in community-acquired and hospital-acquired episodes, were independent risk factors for the development of bacterial pneumonia. The case-fatality rate observed in our study was 27%. On stepwise logistic regression analysis, T CD4+ cell counts < or = 100/mm3 (p = .02), neutropenia (p = .04), PO2 arterial level < or = 70 mm Hg (p = .01), and Karnofsky score < or = 50 (p = .04) were independent indicators of mortality. According to a personally developed prognostic score, 211 episodes of pneumonia (60%) were classified as mild, 63 (18%) as moderate, and 76 (22%) as severe. Clinicians must carefully evaluate those variables that can influence the prognosis of bacterial pneumonia to make early identification of affected patients and to promptly establish the most appropriate therapeutic strategy in each case.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Case-Control Studies; CD4 Lymphocyte Count; Community-Acquired Infections; Confidence Intervals; Cross Infection; Female; Humans; Karnofsky Performance Status; Length of Stay; Liver Cirrhosis; Logistic Models; Male; Odds Ratio; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Risk Factors; Smoking; Substance Abuse, Intravenous; Survival Analysis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Bacterial Infections; Humans; Liver Cirrhosis; Peritonitis; Trimethoprim, Sulfamethoxazole Drug Combination