Antibiotic Prophylaxis for Upper Gastrointestinal Bleed in Liver Cirrhosis; Less May Be More.

INTRODUCTION: Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has been shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics. Seven days of antibiotics are generally recommended but very few studies have compared antibiotic duration to clinical outcomes in current available scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on patient outcomes. METHODS: We conducted a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010 to 2018. Patients were divided into three cohorts based on duration of antibiotic administration for prophylaxis: 1-3 days of antibiotics, 4-6 days of antibiotics and 7 days or more of antibiotics. Rates of infection diagnosis within 30 days, rebleeding, and mortality were compared between the three groups with Chi square, Fisher Exact and Kruskall-Wallace tests. Multivariable analysis was conducted to evaluate independent risk factors for infection. RESULTS: Medical charts of 980 patients with cirrhosis and upper GI bleeding during the study period were reviewed. A total of 303 with upper gastrointestinal bleeding were included in the final sample, of these 243 patients received antibiotics for prophylaxis and were included for analysis. Seventy-seven patients received antibiotic therapy for 3 days or less, 69 patients for 4-6 days, and 97 patients longer than 6 days. The three groups were well matched in demographic and clinical variables. Twenty-seven patients developed infections within 30 days of bleeding. MELD-Na score at presentation and presence of ascites were associated with infection within 30 days. Rates of infection were not statistically different between the three antibiotic groups (p = 0.78). In the thirty days following the GI bleed, pneumonia was the most diagnosed infection (eleven patients) followed by urinary tract infections (eight patients). Four patients developed spontaneous bacterial peritonitis and three were diagnosed with bacteremia. There was no difference in time to infection (Kruskall Wallace test p = 0.75), early re-bleeding (p = 0.81), late re-bleeding (p = 0.37) and in-hospital mortality (p = 0.94) in the three groups. Six patients in the cohort developed C. Difficile infection; no patient in the short antibiotic group developed C. Difficile infection. CONCLUSION: Short course of antibiotics for prophylaxis (3 days) appears safe and adequate for prophylaxis in patients with cirrhosis with upper gastrointestinal bleeding if there is no active infection.

Efficacy and Toxicity Profile of Carfilzomib-Based Regimens for Treatment of Newly Diagnosed Multiple Myeloma: A Systematic Review.

Carfilzomib (CFZ) is a proteasome inhibitor currently approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Multiple trials are ongoing to evaluate its efficacy and safety in newly diagnosed multiple myeloma (NDMM). The use of CFZ-based two- or three-drug combination regimens as induction for the management of NDMM is an emerging approach. CFZ-based regimens include combinations of immunomodulators, alkylating agents, and monoclonal antibodies along with dexamethasone. In this review, we assess the efficacy and toxicity of CFZ-based regimens in NDMM. We reviewed a total of 27 studies (n=4538 patients) with overall response rates (ORR) ranging between 80% and 100%. Studies evaluating the combination of CFZ with daratumumab reported an ORR of approximately 100%. Achievement of minimal residual disease (MRD) negativity, measured by multi-parameter flow cytometry (MPFC), ranged between 60% and 95% in 4 (n=251) out of 6 studies that measured MRD-negativity. The interim results of the ENDURANCE trial failed to show superior efficacy and progression-free survival (PFS) of carfilzomib-lenalidomide when compared to bortezomib-lenalidomide combination, albeit with a lower incidence of neuropathy. Hematological toxicity was the most common adverse event observed with these regimens, and the most common non-hematological adverse events were related to cardiovascular and electrolyte disturbances. We need to further evaluate the role of CFZ in NDMM by conducting more Phase III trials with different combinations.

Concomitant use of blinatumomab and donor lymphocyte infusion for mixed-phenotype acute leukemia: a case report with literature review.

Blinatumomab and donor lymphocyte infusion (DLI) combination is a promising cancer therapy, whereby blinatumomab might achieve an initial reduction in leukemic-cell burden using T cells, and after tumor clearance, DLI can potentially stimulate the donor immune system to achieve longer lasting remission. Here, we present a 51-year-old female with mixed phenotype acute leukemia who had a hematologic relapse 3 months after she received total body irradiation-based myeloablative allogeneic hematopoietic stem cell transplantation from an unrelated human leukocyte antigen matched (10/10) donor and achieved complete remission with minimal residual disease negativity by multi-parameter flow cytometry using the combination of blinatumomab and DLI. To the best of our knowledge, this is the first report to describe the use of blinatumomab and DLI combination therapy in the treatment of B/myeloid mixed phenotype acute leukemia.

Acute Renal Failure due to Organophosphate Poisoning: A Case Report.

Organophosphate (OP) poisoning is a commonly seen condition in many countries. OP poisoning classically presents with symptoms of cholinergic excess. It can rarely affect other organ systems but when it does, it can worsen a patient's overall prognosis. We present a case of a 23-year-old man with an extremely rare case of acute kidney injury due to OP, who was successfully treated with a combination of hemodialysis, atropine and pralidoxime days after OP poisoning with reservations on the aging process.

Antibiogram of Medical Intensive Care Unit at Tertiary Care Hospital Setting of Pakistan.

OBJECTIVE:  To determine the frequency of micro-organisms causing sepsis as well as to determine the antibiotic susceptibility and resistance of microorganisms isolated in a medical intensive care unit. MATERIALS AND METHODS:  This is a cross-sectional analysis of 802 patients from a medical intensive care unit (ICU) of Shifa International Hospital, Islamabad, Pakistan over a one-year period from August 2015 to August 2016. Specimens collected were from blood, urine, endotracheal secretions, catheter tips, tissue, pus swabs, cerebrospinal fluid, ascites, bronchoalveolar lavage (BAL), and pleural fluid. All bacteria were identified by standard microbiological methods, and antibiotic sensitivity/resistance was performed using the disk diffusion technique, according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Data was collected using a critical care unit electronic database and data analysis was done by using  the Statistical Package for Social Sciences (SPSS), version 20 (IBM SPSS Statistics, Armonk, NY). RESULTS:  Gram-negative bacteria were more frequent as compared to gram-positive bacteria. Most common bacterial isolates were Acinetobacter (15.3%), Escherichia coli (15.3%), Pseudomonas aeruginosa (13%), and Klebsiella pneumoniae (10.2%), whereas Enterococcus (7%) and methicillin-resistant staphylococcus aureus (MRSA) (6.2%) were the two most common gram-positive bacteria. For Acinetobacter, colistin was the most effective antibiotic (3% resistance). For E.coli, colistin (0%), tigecycline (0%), amikacin (7%), and carbapenems (10%) showed low resistance. Pseudomonas aeruginosa showed low resistance to colistin (7%). For Klebsiella pneumoniae, low resistance was seen for tigecycline (0%) and minocycline (16%). Overall, ICU mortality was 31.3%, including miscellaneous cases. CONCLUSION:  Gram-negative infections, especially by multidrug-resistant organisms, are on the rise in ICUs. Empirical antibiotics should be used according to the local unit specific data. Constant evaluation of current practice on basis of trends in multidrug resistance and antibiotic consumption patterns are essential.