Antibiotic Treatment in Complicated Appendicitis: Can It Be Optimized?

BACKGROUND: The management of complicated appendicitis is inconclusive. Guidelines have not been established for the use of personalized antibiotic treatment. OBJECTIVES: To investigate specific risk factors to consider during the initial first-choice antibiotic therapy in children with complicated appendicitis. METHODS: This study included all pediatric patients younger than 18 years of age who underwent a laparoscopic appendectomy during 2012-2022 at a single tertiary medical center. RESULTS: In total, 300 pediatric patients underwent laparoscopic appendectomy due to complicated appendicitis. The patients were treated with ceftriaxone + metronidazole (CM). For 57 (19%) patients, the empirical treatment was changed to tazobactam/piperacillin (TP) due to resistant bacteria or clinical deterioration. The presence of generalized peritonitis during surgery and C-reactive protein (CRP) levels above 20 mg/L at admission were identified as risk factors for changing the antibiotic regimen from CM to TP. CONCLUSIONS: Generalized peritonitis and CRP > 20 gr/L were highly correlated with changing the antibiotic regimen to TP. For such patients, initial treatment with TP may result in clinical improvement and shorter hospitalization.

Intraperitoneal vancomycin plus levofloxacin for the treatment of peritoneal dialysis-related peritonitis in patients with no response to cefazolin plus ceftazidime.

INTRODUCTION: Peritoneal dialysis-related peritonitis (PDRP) should be treated as soon as possible by an empirical regimen without waiting for effluent bacterial culture results. We retrospectively investigated patients treated with vancomycin plus levofloxacin as a treatment regimen if there was no response to cefazolin plus ceftazidime. MATERIALS AND METHODS: We collected records of adult patients with PDRP from January 1, 2013, to November 30, 2020. The characteristics of episodes of PDRP with no response to cefazolin plus ceftazidime treated by intraperitoneal (IP) injection of vancomycin plus levofloxacin were analyzed. RESULTS: 118 episodes of PDRP were recorded, among which 115 episodes were treated with IP antibiotics. 93 episodes were treated with cefazolin plus ceftazidime. In 38 episodes, treatment was switched to IP injection of vancomycin plus levofloxacin if there was no response to cefazolin plus ceftazidime. 26/38 (68.4%) episodes were cured by vancomycin plus levofloxacin. Fever, diabetes, fasting glucose, a decrease in effluent leukocytes on day 3 and day 5, and Charlson Comorbidity Index (CCI) scores were significantly different between uncured and cured episodes. No variable was associated with treatment failure after multiple logistic regression. Fever, diabetes, a decrease in effluent leukocytes on day 3, and CCI score were associated with treatment failure after univariable logistic regression. CONCLUSION: Vancomycin plus levofloxacin may be effective if patients are not responsive to cefazolin plus ceftazidime.

16S rRNA Next-Generation Sequencing May Not Be Useful for Examining Suspected Cases of Spontaneous Bacterial Peritonitis.

Background and Objectives: Ascites, often associated with liver cirrhosis, poses diagnostic challenges, particularly in detecting bacterial infections. Traditional methods have limitations, prompting the exploration of advanced techniques such as 16S rDNA next-generation sequencing (NGS) for improved diagnostics in such low-biomass fluids. The aim of this study was to investigate whether the NGS method enhances detection sensitivity compared to a conventional ascites culture. Additionally, we aimed to explore the presence of a microbiome in the abdominal cavity and determine whether it has a sterile condition. Materials and Methods: Ten patients with clinically suspected spontaneous bacterial peritonitis (SBP) were included in this study. A traditional ascites culture was performed, and all ascites samples were subjected to 16S ribosomal RNA gene amplification and sequencing. 16S rRNA gene sequencing results were interpreted by comparing them to positive and negative controls for each sample. Results: Differential centrifugation was applied to all ascites samples, resulting in very small or no bacterial pellets being harvested. The examination of the 16S amplicon sequencing libraries indicated that the target amplicon products were either minimally visible or exhibited lower intensity than their corresponding negative controls. Contaminants present in the reagents were also identified in the ascites samples. Sequence analysis of the 16S rRNA gene of all samples showed microbial compositions that were akin to those found in the negative controls, without any bacteria isolated that were unique to the samples. Conclusions: The peritoneal cavity and ascites exhibit low bacterial biomass even in the presence of SBP, resulting in a very low positivity rate in 16S rRNA gene sequencing. Hence, the 16S RNA sequencing method does little to enhance the rate of positive samples compared to traditional culture methods, including in SBP cases.

Ascites fluid calprotectin level is highly accurate in diagnosing spontaneous bacterial peritonitis: a preliminary proof of concept prospective study.

Ascites is the most common complication of liver cirrhosis. Spontaneous bacterial peritonitis (SBP) is a common complication of ascites. The diagnosis is made by an ascitic fluid polymorphonuclear (PMN) cell count of ≥ 250/mm3. However, no other diagnostic test is present for the diagnosis of SBP. The aim of the study present study is to assess the diagnostic yield of ascitic calprotectin in SBP, and to explore whether it can predict disease stage. We performed a single center proof-of-concept prospective study including all patients with cirrhosis and ascites who underwent paracentesis. Overall, 31 patients were included in the study. Eight patients had SBP vs. 23 patients without SBP. Ascitic calprotectin level was 77.4 ± 86.5 µg/mL in the SBP group, as compared to 16.1 ± 5.6 µg/mL in the non-SBP group (P = 0.001). An ascitic calprotectin cut-off value of > 21 µg/mL was associated with sensitivity and specificity of 85.7% and 89.5%, respectively, with ROC of 0.947 (95% CI 0.783 to 0.997, P < 0.0001). Notably, ascitic calprotectin did not had a prognostic value in cirrhosis stage and prognosis. Ascitic calprotectin was highly accurate in the diagnosis of SBP. It can be a serve as adjunct for indefinite cases of SBP.

Diagnostic Paracentesis Within 1 Day Is Associated With Reduced Mortality and Length of Hospital Stay in Patients with Cirrhosis and Ascites.

Spontaneous bacterial peritonitis (SBP) is the most common infection in patients with cirrhosis and is associated with high mortality. Although recent literature reports mortality benefits to early diagnostic paracentesis, current guidelines do not offer specific recommendations for how quickly diagnostic paracentesis should be performed in patients with cirrhosis and ascites who are admitted to the hospital. Therefore, we conducted a systematic review and meta-analysis to evaluate outcomes among patients admitted to the hospital with cirrhosis and ascites receiving paracentesis within ≤ 12, ≤ 1 day, and > 1 day. Eight studies with 116,174 patients were included in the final meta-analysis. The pooled risk of in-hospital mortality was significantly lower in patients who underwent early (≤ 12 h or ≤ 1 day) compared to delayed (> 12 h or > 1 day) paracentesis (RR: 0.69, p < 0.00001), and in patients who underwent paracentesis compared to no paracentesis (RR: 0.74, p < 0.00001). On subgroup analysis, in-hospital mortality was significantly lower in both paracentesis within ≤ 12 h (RR: 0.61, p = 0.02) vs. > 12 h, and within ≤ 1 day (RR: 0.70, p < 0.00001) vs. > 1 day. While there was a trend towards decreased mortality in those undergoing paracentesis within ≤ 12 h compared to ≤ 1 day, the difference did not reach statistical significance. The length of hospital stay was significantly shorter by 5.38 days in patients who underwent early (≤ 12 h) compared to delayed (> 12 h) paracentesis (95% CI 4.24-6.52, p < 0.00001). Early paracentesis is associated with reduced mortality and length of hospital stay. We encourage providers to perform diagnostic paracentesis in a timely manner, at least within 1 day of hospital admission, for all patients with cirrhosis and ascites.

Peritoneal Dialysis-Associated Peritonitis Caused by Achromobacter xylosoxidans: A Case Report and Literature Review.

Achromobacter xylosoxidans is a gram-negative bacterium that is responsible for rare peritonitis associated with peritoneal dialysis (PD). We present a case of a 64-year-old woman with a medical history of end-stage renal disease undergoing PD who was admitted to the emergency department with abdominal pain and nausea. Physical examination and laboratory studies revealed peritoneal signs and laboratory abnormalities consistent with peritonitis. Intraperitoneal catheter dysfunction was identified and subsequently resolved via laparoscopy. Following a peritoneal fluid culture, A xylosoxidans was identified, leading to the initiation of intraperitoneal meropenem treatment. After an initial improvement, the patient developed an ileus and recurrent abdominal symptoms, and further peritoneal cultures remained positive for A xylosoxidans. Subsequent treatment included intravenous meropenem and vancomycin for Clostridium difficile colitis. Owing to the high likelihood of biofilm formation on the PD catheter by A xylosoxidans, the catheter was removed, and the patient transitioned to hemodialysis. Intravenous meropenem was continued for 2 weeks post-catheter removal. This case highlights the challenges in managing recurrent peritonitis in PD patients caused by multidrug-resistant A xylosoxidans. A high index of suspicion, appropriate microbiological identification, and targeted intraperitoneal and systemic antibiotic treatment, along with catheter management, are crucial in achieving a favorable outcome in such cases.

Prognosis of spontaneous bacterial peritonitis in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of death from cancer worldwide. Spontaneous bacterial peritonitis (SBP) is associated with poor prognosis. This study aimed to evaluate risk factors, differences in clinical characteristics and prognosis of SBP in patients with HCC in comparison with non-HCC patients. METHODS: This study was conducted on patients with cirrhosis who were admitted to hospital with SBP. The patients were divided into two groups: SBP group with HCC (n = 150) and SBP group without HCC (n = 250). RESULTS: Men and women accounted for 72% and 28% (n = 108 and 42, respectively) of the population in SBP group with HCC with mean age 55.8 ± 13.1 years. They accounted for 68.4% and 31.6% (n = 171 and 79, respectively) in the SBP group without HCC with mean age 56.8 ± 10.5 years. In-hospital mortality was 25.3% in the SBP group with HCC and 18.8% in SBP group without HCC. Gastrointestinal bleeding was the most common cause of death in both groups. No significant difference was observed in patient outcomes between the two studied groups. The deceased patients had significantly higher levels of leukocytes and neutrophils in ascitic fluid as well as a higher frequency of positive culture results than in patients who survived (p < 0.001). However, there was no significant difference in protein level in ascitic fluid or causative organism between patients who survived and those who died (p = 0.63 and 0.19, respectively). CONCLUSIONS: Prognosis of SBP in patients with HCC seemed similar to that in patients without HCC.

Risks of Proton Pump Inhibitors in Patients with Cirrhosis: Please Peruse the Indications.

The use of proton pump inhibitor (PPI) in cirrhotic patients can be associated with increased risks of long-term mortality, decompensation, hepatic encephalopathy, spontaneous bacterial peritonitis, and infection, but not with short-term mortality. Ensure clear indications at lowest effective dose of is mandatory for the use of PPI among cirrhotic patients.

Proton Pump Inhibitors Increases Longitudinal Risk of Mortality, Decompensation, and Infection in Cirrhosis: A Meta-Analysis.

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are frequently prescribed to cirrhotic patients, but there is limited longitudinal evidence regarding their effects. This study aimed to assess the impact of PPIs on adverse events in cirrhotic patients. METHODS: A comprehensive search was conducted using the Medline and Embase databases to identify relevant articles. Pooled hazard ratios (HRs) using DerSimonian and Laird random-effects model were calculated to evaluate the risk of adverse events such as long-term mortality, hepatic decompensation, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and overall infection in cirrhotic patients with PPI use. RESULTS: The analysis included 28 studies with 260,854 cirrhotic patients. The prevalence of PPI use among cirrhotic patients was 55.93%. The use of PPIs was not significantly associated with short-term mortality in cirrhotic patients. However, long-term mortality (HR 1.321, 95% CI 1.103-1.581, P = 0.002), decompensation (HR 1.646, 95% CI 1.477-1.835, P < 0.001), HE (HR 1.968, 95% CI 1.372-2.822, P < 0.001), SBP (HR 1.751, 95% CI 1.649-1.859, P < 0.001), and infection (HR 1.370, 95% CI 1.148-1.634, P < 0.001) were significantly associated with PPI use. Sensitivity analysis with prospective studies yielded similar results. CONCLUSION: PPIs should be reserved for appropriate indications at lowest effective dose for cirrhotic patients due to the potential harm.

Perihepatitis as an Initial Manifestation of Systemic Lupus Erythematosus.

A 25-year-old man presented with a fever and right upper quadrant abdominal pain. Computed tomography (CT) of the abdomen revealed diffuse perihepatic capsular enhancement, suggesting perihepatitis. Although the patient was a man, Fitz-Hugh-Curtis syndrome was suspected based on the CT findings. Treatment with several antibiotics was ineffective. Urinary tract infection was ruled out due to negative urinary bacterial screening and careful history taking. He was finally diagnosed with systemic lupus erythematous (malar rash, pleuritis, positive antinuclear antibody, and positive anti-ds-DNA antibody). Perihepatitis resolved quickly with high-dose prednisolone. Perihepatitis may be the first manifestation of SLE.

Successful treatment of peritonitis caused by Acremonium species without catheter removal: Case report and literature review.

INTRODUCTION: It is a rare case of continuous ambulatory peritoneal dialysis-related peritonitis associated with Acremonium spp infection. CASE PRESENTATION: Symptoms of Acremonium infection peritonitis are hidden and atypical, leucocytes in ascites are moderately elevated, and general bacterial culture difficulty obtains positive results. In this report, a patient with peritoneal dialysis-related peritonitis caused by Acremonium species was successfully treated without catheter removal in our hospital. The organism species was cultured from a catheter and PD effluent fluid. The patient's peritonitis did not relapse within 6 months. CONCLUSIONS: Once a patient on peritoneal dialysis was infected with fungal peritonitis, the outcome was usually to remove the tube and stop peritoneal dialysis. In this case, our experience is that using a catheter-salvage therapy method, we can successfully cure PD-related peritonitis associated with Acremonium sp.

Systematically analysis of decompensated cirrhotic patients with spontaneous bacterial peritonitis to identify diagnostic and prognostic indexes.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis. The diagnosis of SBP is still mostly based on ascites cultures and absolute ascites polymorphonuclear (PMN) cell count, which restricts the widely application in clinical settings. This study aimed to identify reliable and easy-to-use biomarkers for both diagnosis and prognosis of cirrhotic patients with SBP. METHODS: We conducted a retrospective study including 413 cirrhotic patients from March 2013 to July 2022 in the First Affiliated Hospital of Guangxi Medical University. Patients' clinical characteristics and laboratory indices were collected and analyzed. Two machine learning methods (Xgboost and LASSO algorithms) and a logistic regression analysis were adopted to screen and validate the indices associated with the risk of SBP. A predictive model was constructed and validated using the estimated area under curve (AUC). The indices related to the survival of cirrhotic patients were also analyzed. RESULTS: A total of 413 cirrhotic patients were enrolled in the study, of whom 329 were decompensated and 84 were compensated. 52 patients complicated and patients with SBP had a poorer Child-Pugh score (P < 0.05). Patients with SBP had a greater proportion of malignancies than those without SBP(P < 0.05). The majority of laboratory test indicators differed significantly between patients with and without SBP (P < 0.05). Albumin, neutrophil-to-lymphocyte ratio (NLR), and ferritin-to-neutrophil ratio (FNR) were found to be independently associated with SBP in decompensated cirrhotic patients using LASSO algorithms, and logistic regression analysis. The model established by the three indices showed a high predictive value with an AUC of 0.808. Furthermore, increased neutrophils, ALP, and C-reactive protein-to-albumin ratio (CAR) were associated with the shorter survival time of patients with decompensated cirrhosis, and the combination of these indices showed a greater predictive value for cirrhotic patients. CONCLUSIONS: The present study identified FNR as a novel index in the diagnosis of SBP in decompensated patients with cirrhosis. A model based on neutrophils, ALP and CAR showed high performance in predicting the prognosis of patients with decompensated cirrhosis.

In vivo efficacy of pyochelin-mediated delivery of zingerone in Pseudomonas aeruginosa-induced peritonitis.

Aim: The efficacy of a pyochelin-zingerone conjugate (PZC) against Pseudomonas aeruginosa in vivo in a mouse model of peritonitis, as well as mode of action in vitro, were investigated. Methods & results: Intraperitoneal administration of PZC (220 mg kg-1 b.wt.) resulted in a significant reduction in bacterial count in liver tissue by 2 log10 on the 4th day post infection. This was supported by reduced levels of inflammatory markers, liver function, inflammatory cytokines and improved histopathology. PZC showed its ability to disrupt the cellular membrane, increase permeability of the membrane and leakage of intracellular contents of P. aeruginosa, resulting in its death. Conclusion: The present study reports the hepatoprotective potential of PZC in an experimental model of P. aeruginosa-induced peritonitis.

Nosocomial spontaneous bacterial peritonitis is associated with high mortality - a systematic review and meta-analysis.

INTRODUCTION: It is unclear if Nosocomial Spontaneous Bacteria Peritonitis (NSBP) is associated with higher mortality compared with community acquired spontaneous bacterial peritonitis. METHODS: Database search from inception to May 2022 was conducted. The databases included MEDLINE, EMBASE, Cochrane registry of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Inclusion criteria were as follows: adult patients, age >18 years, with a diagnosis of NSBP. Pooled estimates of mortality were calculated following the restricted maximum likelihood method. The mortality rate between NSBP and CA-SBP was reported as odds ratio (OR) and 95% confidence interval (CI). Data synthesis was obtained using random effects meta-analysis. Heterogeneity was reported as I2. RESULTS: A total of 482 unique titles were screened. Twenty-two articles were included. A total of 2,145 patients with NSBP were included. Patients were followed for a median of 90 days. The pooled mortality rate of NSBP was 52.51% (95% CI 42.77-62.06%; I2 83.72%). Seven studies compared the mortality outcome of patients with NSBP and CA-SBP. NSBP was significantly associated with a higher rate of mortality (OR 2.78, 95% CI 1.87-4.11; I2 36.00%). CONCLUSION: NSBP was associated with higher mortality rate compared to CA-SBP, which could be due to a higher rate of resistance organisms.

Association of serum sodium and 24-hour urinary sodium level with the severity and complications of ascites in cirrhotic patients.

Hyponatremia is an independent predictor of mortality in cirrhotic patients but little is known regarding the relationship between the level of serum sodium and 24-hour urinary sodium with the development of severity and complications of cirrhotic ascites. To observe the association of serum sodium and 24-hour urinary sodium levels with different grades of ascites and its complications in cirrhotic patients. In the department of Gastroenterology in a tertiary care hospital, this cross-sectional study was conducted from April 2019 to September 2020. A total of 96 admitted cirrhotic patients with ascites were enrolled in this study by consecutive sampling. Out of 96 patients with cirrhotic ascites, 48 patients had mild, moderate, and severe ascites and 48 patients had complications of ascites like refractory ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome. The mean serum sodium level was 131.69 ±â€…4.90 and 124.88 ±â€…5.67 mmol/L and the 24-hour urinary sodium level was 76.82 ±â€…45.64 and 35.26 ±â€…22.57 mmol/L in uncomplicated and complicated ascites groups respectively with P value < .001. In grade 1, grade 2, and grade 3 ascites, there was a significant (P = .001), association between mean serum sodium (mmol/L) level (R -0.777) and 24-hour urine sodium (mmol/L) level (R -0.704) but no significant difference was seen when refractory ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome were considered. In our finding, low serum sodium and low 24-hour urinary sodium levels were associated with the development of severe complications of cirrhotic ascites. Hence, Serum sodium and 24-hour urinary sodium levels can be good predictors of grading and complications of cirrhotic ascites.

Antimicrobial-loaded biodegradable nanoemulsions for efficient clearance of intracellular pathogens in bacterial peritonitis.

Intracellular pathogenic bacteria use immune cells as hosts for bacterial replication and reinfection, leading to challenging systemic infections including peritonitis. The spread of multidrug-resistant (MDR) bacteria and the added barrier presented by host cell internalization limit the efficacy of standard antibiotic therapies for treating intracellular infections. We present a non-antibiotic strategy to treat intracellular infections. Antimicrobial phytochemicals were stabilized and delivered by polymer-stabilized biodegradable nanoemulsions (BNEs). BNEs were fabricated using different phytochemicals, with eugenol-loaded BNEs (E-BNEs) affording the best combination of antimicrobial efficacy, macrophage accumulation, and biocompatibility. The positively-charged polymer groups of the E-BNEs bind to the cell surface of macrophages, facilitating the entry of eugenol that then kills the intracellular bacteria without harming the host cells. Confocal imaging and flow cytometry confirmed that this entry occurred mainly via cholesterol-dependent membrane fusion. As eugenol co-localized and interacted with intracellular bacteria, antibacterial efficacy was maintained. E-BNEs reversed the immunosuppressive effects of MRSA on macrophages. Notably, E-BNEs did not elicit resistance selection after multiple exposures of MRSA to sub-therapeutic doses. The E-BNEs were highly effective against a murine model of MRSA-induced peritonitis with better bacterial clearance (99 % bacteria reduction) compared to clinically-employed treatment with vancomycin. Overall, these findings demonstrate the potential of E-BNEs in treating peritonitis and other refractory intracellular infections.

Significance of Serum Procalcitonin and C-Reactive Protein in the Diagnosis and Prediction of Spontaneous Bacterial Peritonitis in Decompensated Chronic Liver Disease.

The role of serum procalcitonin (PCT) and C-reactive protein (CRP) levels in the diagnosis of spontaneous bacterial peritonitis (SBP) with decompensated chronic liver disease (CLD) has been a subject of debate. The purpose of this cross-sectional, observational study was to evaluate the significance of CRP and PCT for the diagnosis and prediction of SBP in decompensated CLD patients. Fifty patients with ascites due to decompensated CLD were enrolled conveniently from the department of Gastrointestinal, Hepatobiliary and Pancreatic disorders (GHPD), BIRDEM General Hospital, Bangladesh from July 2019 to July 2020. Of these decompensated CLD patients with SBP were enrolled as the case group and without SBP as control group. Diagnostic and predictive value of PCT and CRP were calculated using the different statistical analysis. Among 50 patients, SBP was diagnosed in 9 patients (18.0%). The ROC analysis results yielded that the optimum cut off value for PCT was 0.67ng/ml and sensitivity, specificity, positive predictive value, negative predictive value, accuracy, AUC were 88.9%, 90.2%, 66.6%, 97.3, 90%, 0.947 respectively. On the contrary the optimum cut off value for CRP was 57.4mg/L and sensitivity, specificity, positive predictive value, negative predictive value, accuracy, AUC were 77.8%, 85.4%, 53.8%, 94.5%, 84%, 0.859 respectively. Our results indicate that the value of serum PCT and CRP were reliable to diagnose SBP in ascites due to decompensated CLD. Serum PCT and CRP level measurements may provide an early good diagnostic test for SBP in decompensated CLD patients.