Efficacy and Safety Assessment of Antifungal Sequential Therapy from Micafungin to Liposomal Amphotericin B for Antibiotics-Refractory Febrile Neutropenia in Patients with Hematologic Malignancies

Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.

Retrospective study of the incidence, risk factors, treatment outcomes of bacterial infections at uncommon sites in cirrhotic patients

BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical variables.METHODS We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care center.BIs were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two groups.RESULTS In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical BI.Atypical BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the disease.Hence,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.

Efficacy and safety of itraconazole as empirical antifungal therapy in febrile neutropenic patients with hematologic malignancies： an open-lable, multicenter, observational trial in a Chinese cohort

Background Invasive fungal infection （IFI） is a common and fatal complication in neutropenic patients with hematological malignancy. Empirical antifungal therapy is widely used in practice due to the difficulty of pathogens determination and illness of the hosts. The aim of this study was to evaluate the efficacy and safety of itraconazole as empirical antifungal therapy for persistent fever in neutropenic patients with hematologic malignancies. Methods Two hundred and seventy-four patients with hematologic malignancies who had suspected fungal infections were enrolled in 18 centers across China between April 2008 and April 2009. Empirical antifungal therapy with intravenous itraconazole 200 mg twice daily was given for the first two days, followed by 200 mg once daily for the next 12 days. Oral itraconazole solution was sequential for follow-up therapy if necessary. Five composite end points were evaluated for the response, which was more restrictive and adopted for the first time in such study in China. Results The intent-to-treat analysis included data from 274 patients （full analysis set, FAS）, of whom 248 were included as the per-protocol population （PPS）. As the composite end point of five indices was concerned, the overall response rate was 43.4%. Seperately, defervescence was achieved in 90% of patients in which 55.5% occured during neutropenia. The mean time to defervescence was 2.71 days. Absence of breakthrough IFI during drug administration or within the first 7 days after study completion was observed in 71.5% of patients. Fifty-five point five percent patients with IFI at baseline was successfully treated. Ninety point five percent patients survived for at least 7 days after completing the study. PPS analysis revealed that the duration of neutropenia 〉10 days was a statistically significant negative predictor for the response. The withdrawal rate due to drug-related toxicity or lack of efficacy was 11.0%. The incidence of adverse events was 22.6%, in which 11.6% was study drug related. The most frequent adverse events were mild to moderate liver toxicity. Conclusion Itraconazole shows desirable efficacy and safety as empirical antifungal therapy for febrile neutropenic patients with hematologic malignancies.

Epidemiology of methicillin-resistant Staphylococcus aureus infection and empirical antibiotic therapy for MRSA infection： multicenter investigation

Background The epidemiology of methicillin-resistant Staphylococcus aureus （MRSA） maybe changed by strict infection control measures,and the impact of empirical antibiotic therapy on the outcomes of MRSA infection was not clear.We aimed to investigate the present epidemiological status of MRSA infection and empirical antibiotic therapy for MRSA infection in university teaching hospitals in China's Mainland.Methods The present study was a multicenter prospective observational study conducted in five university teaching hospitals.Patients who were consecutively admitted to the intensive care unit and signed a consent form from March 3,2011 to May 31,2011 were included.Patients with age 〈18 years or with a length of hospital stay 〈48 hours were excluded from this study.The following variables were collected or recorded：demographic data,general status,APACHE Ⅱ score of the patient at the time of admission,infections,and the use of antibiotics during a stay.Primary outcomes and prognostic indicators included length of hospital stay and 28-day and 90-day mortality.The differences between the patients with appropriate empirical therapy and patients with inappropriate therapy were analyzed to detect the influences of antibiotic therapy on the prognosis of MRSA infection.Results A total of 682 cases were enrolled.Thirty （66.2%） of 88 MRSA cases were treated with effective antibiotics for MRSA infection; only 20% received appropriate empirical antibiotic treatment.The empirical therapy group compared with the target therapy group had a shorter length of stay,but there were no significant differences in mortality rates.There were no significant differences in the length of hospital stay,length of stay,and 28-day and 90-day mortality between MRSA-infected patients who received or not received effective antibiotics.Two hundred and eighteen cases received sensitive antibiotics for MRSA.Conclusions The MRSA infection rates are at relatively low levels in university teaching hospitals in China.The empirical use of sensitive antibiotics for MRSA infection was at relatively high rate,and there is a tendency of overusing in patients without MRSA infection.On the other hand,the rate of appropriate empirical antibiotic therapy for patients with MRSA infection is relatively low.

Organisms causing spontaneous bacterial peritonitis in children with liver disease and ascites in Southern Iran

AIM： To determine the causative agents of spontaneous bacterial peritonitis （SBP） in children with liver disease and ascites in our center. METHODS： During a 2.5 year period, from September 2003 to March 2006, 12 patients with 13 episodes of SBP were studied. In all cases at the time of admission serum albumin and glucose, urinalysis and urine culture was performed. Analysis [white blood cell （WBC） count with differential, albumin, glucose], gram stain, culture by BACTEC method and antibiogram was done on ascitic fluids. Abdominal paracentesis was repeated after 48 h of antibiotic therapy for bacteriologic assay. The patients were followed for at least three months in a gastroenterology clinic. RESULTS： There were 7 girls （58%） and 5 boys （42%） with a median age of 5.2 years （range, 6 mo to 16 years）. All cases had positive ascitic fluid culture. Gram stain was positive in 5 （38.5%） of them. The isolated organisms were S. pneumoniae in 5 （38.5%）, E. coli in 2 （15.3%）, S. viridans in 2 （15.3%）, and K. pneumoniae, H. influenza, Enterococci, and nontypable Streptococcus each in one （7.7%）. All of them except Enterococci were sensitive to ciprofloxacin and ceftriaxone. All ascitic fluid cultures were negative after 48 h of antibiotic therapy. CONCLUSION： S. pneumoniae is the most common cause of SBP in the pediatric age group and we recommend a third generation cephalosporine （e.g., Ceftriaxlone or Cefotaxime） for empirical therapy in children with SBP.

Nystatin-Neomycin-Polymyxin B Combination:Efficacy and Tolerance as 1st-Line Local Treatment of Infectious Vaginitis

Objective: To evaluate the efficacy and tolerance of a local treatment combining two antibacterials and one antifungal in patients with a clinical presentation suggesting infectious vaginitis. Patients and methods: 169 patients presenting with clinical criteria for vaginitis were included in an open, multicenter trial. Vaginal samples were taken for microbiological analyses and a triple-combination product of nystatin, neomycin and polymyxin B was then started as local treatment, without waiting for the test results. The treatment was continued with the usual dosage (1 vaginal capsule at bedtime for 12 days) for vaginal infections in the scope of the combination product with approved labeling. A second vaginal sample was performed at the end of the treatment. The main efficacy criterion was the clinical success rate (cure or improvement of the clinical signs and symptoms) according to the investigator.Results: 93 patients were included in the efficacy population. Non-exclusively fungal vaginitis (strictly bacterial or bacterial + fungal) represented 31.2% of the cases. The clinical success rate was 97.8% according to the investigator and 95.7% according to the patients. The microbiological success rate was 81.3%, with no differences between etiologies (Candida spp., bacteria or both). The combination product was well-tolerated, despite the local inflammation before treatment. Discussion and conclusion: Given the etiological diversity of vaginitis, this trial supports the efficacy of a triple-combination product (nystatin, neomycin, polymyxin B) as a first-line local treatment of Candida, bacterial or mixed vaginitis.