Clinical Outcomes of Trimethoprim/Sulfamethoxazole in Critically Ill Patients with Stenotrophomonas maltophilia Bacteremia and Pneumonia Utilizing Renal Replacement Therapies.

Background: The clinical outcomes of usual doses of Trimethoprim-sulfamethoxazole (TMP/SMZ) for treating S. maltophilia in critically ill patients on renal replacement therapies (RRT) have not been established. We sought to assess the clinical outcomes of TMP/SMZ in patients with sepsis utilizing RRT. Methods: A retrospective study was performed on all critically ill adult patients with S. maltophilia infections who received RRT between May 2015 and January 2022. The primary endpoint was clinical cure while the secondary endpoints were microbiologic cure, 30-day infection recurrence, and mortality. Results: Forty-five subjects met the inclusion criteria. The median age was 70.0 [interquartile range (IQR): 63.5-77] years, 57.8% were males, and the median body mass index was 25.7 [IQR: 22-30.2] kg/m2. Clinical success and failure were reported in 18 (40%) and 27 (60%) cases, respectively. There was no significant difference between the 30-day reinfection rates of both groups; however, mortality was significantly higher in the clinical failure group, involving 12 patients (44.4%), versus none in the clinical success group (p = 0.001). The median daily dose of TMP/SMZ upon continuous veno-venous hemofiltration was 1064 [IQR: 776-1380] mg in the clinical cure group vs. 768 [IQR:540-1200] mg in the clinical failure group (p = 0.035). Meanwhile, the median dose for those who received intermittent hemodialysis was 500 [IQR: 320-928] mg in the clinical success group compared to 640 [IQR: 360-1005] mg in the clinical failure group (p = 0.372). A total of 55% experienced thrombocytopenia, 42% hyperkalemia, and 2.2% neutropenia. The multivariable logistic regression analysis showed that the total daily dose at therapy initiation was the only independent factor associated with clinical success after adjusting for different variables including the body mass index [Odds ratio 1.004; 95% confidence interval: (1-1.007), p = 0.044]. Conclusions: Although the S. maltophilia isolates were reported as susceptible, TMP/SMZ with conventional doses to treat bacteremia and pneumonia in critically ill patients utilizing RRT was associated with high rates of clinical and microbiologic failure as well as with mortality. Larger outcomes and pharmacokinetics studies are needed to confirm our findings.

Racial differences in P2Y12 inhibitor responsiveness in patients undergoing neuro-endovascular procedures: A cohort from the Middle East.

BACKGROUND: Data on P2Y12 inhibitors responsiveness from the middle east is scarce. We sought to investigate patient responsiveness to P2Y12 inhibitors within a cohort of major races that characterize the UAE population. The secondary objective was to assess risk factors for hyper and hypo-responsiveness in this population. METHODS: We conducted a cross-sectional study on adults who received either clopidogrel or ticagrelor treatments and had platelet responsiveness testing before undergoing neuro-endovascular interventions at our quaternary care hospital between March 2015 and April 2019. RESULTS: During the study period, 249 subjects met the inclusion criteria. Overall, 17.3 % were hyper-responsive and 25.7 % were hypo-responsive to P2Y12 inhibitors. When comparing between the P2Y12 inhibitors, rates of hyper-responsiveness were significantly higher to ticagrelor when compared to clopidogrel (11 versus 6 %, p = 0.02 respectively). Contrarily, hypo-responsiveness rates were significantly higher in clopidogrel treated patients compared to their ticagrelor treated counterparts (23 versus 2 %, p < .001 respectively). Patients of Middle-Eastern origin showed a significantly higher rate of hypo-responsiveness to both clopidogrel and ticagrelor when compared to other races (41.1 % and 26.7 %, P < 0.001 respectively). Asians showed the highest rates of hyper-responsiveness for both agents. Multivariate logistic regression analysis showed that proton pump inhibitors and statin combination, (OR: 6.39, 95 %CI [1.60, 25.392]), and Middle East vs. Indian subcontinent patients (OR: 4.67, 95 %CI [1.79-12.14]) were independent predictors of hypo-responsiveness to both P2Y12 inhibitors. CONCLUSION: This study demonstrated a high rate of hypo-responsiveness to P2Y12 inhibitors in a UAE cohort of patients undergoing neuro-endovascular procedures. In addition, therapeutic responsiveness to P2Y12 inhibitors varied markedly based on the racial background. Future larger studies are needed to evaluate genetic variations that may contribute to this rate of hypo-responsiveness in our population.

The prevalence of cardiorenal anemia syndrome among patients with heart failure and its association with all-cause hospitalizations: a retrospective single-center study from the Middle East.

Background and aim: Little is known about the burden of cardiorenal syndrome (CRS) and cardiorenal anemia syndrome (CRAS) in the Middle East Region. Furthermore, whether the occurrence rates of CRAS differ across heart failure (HF) phenotypes is not widely investigated. We aimed to examine the prevalence of CRS and CRAS in patients with HF, compare characteristics of patients with CRAS-HFrEF vs. CRAS-HFpEF, and investigate anemia association with 1-year all-cause hospitalizations. Methods: HF patients who visited a multidisciplinary HF clinic at a single center between 10-2015 and 06-2022 (n = 968) were retrospectively included. Differences in rates of CRAS prevalence, and patients' characteristics of those with CRAS-HFrEF vs. CRAS-HFpEF were determined using appropriate testing methods. Generalized estimating equation (GEE) models were used to determine if anemia was associated with higher rates of hospitalization. Results: CRS was prevalent in 34.4% of subjects, while 25.3% had CRAS. CRAS prevalence rates among patients with HFpEF vs. HFrEF were comparable (27.2% vs. 24.2%, p = 0.3). Compared to patients with HFrEF-CRAS, those with HFpEF-CRAS were more likely females (p < 0.001), had a higher burden of hypertension (p = 0.01), and lower hemoglobin (p = 0.02). In an adjusted GEE model, anemia was associated with an average increase of 1.8 admissions in CRS patients (p = 0.015). Conclusion: In patients with HF, 1 in 3 patients presented with CRS, and 1 in 4 patients had CRAS. The prevalence of CRAS was comparable among those HFpEF and HFrEF. Anemia was associated with an increased rate of 1-year all-cause hospitalization in CRS patients.

Clinical outcomes of ceftolozane-tazobactam dosing in patients with sepsis undergoing renal replacement therapies.

Ceftolozane-tazobactam (C/T) recommended dosing in patients undergoing renal replacement therapies (RRT) is lacking evidence. The objective of this study was to evaluate the clinical outcomes of C/T dosing in patients on RRT. MATERIALS AND METHODS: A retrospective descriptive study conducted at our institution between May 1, 2017, and March 15, 2022. The primary endpoint was to determine the clinical cure for patients who received C/T for documented infection while on RRT. The secondary endpoints were the microbiologic cure, 30-day infection recurrence, and 30-day crude mortality. RESULTS: Of the 27 patients who met the inclusion criteria, 17 (63%) were males, median age was 69 (62 - 82) years, and weight 67 (57 - 79) kg. The majority of patients had pneumonia 19 (70.4%) followed by bacteremia 5 (18.5%). Multidrug resistant Pseudomonas spp. was the causative organism of infection in 22 subjects (81.5%). Clinical cure was achieved in 17 subjects (63%). Of the 14 subjects who had their culture repeated, 10 (71.4%) patients had microbiologic cure vs. 4 (28.5%) patients who had a microbiologic failure (p = 0.327). 30-day infection recurrence occurred in 6 (35.3%) patients of the clinical cure group and 2 (20%) patients in the clinical failure group (p = 0.362), while mortality occurred in 5 (29.4%) subjects vs. 7 (70%) in both groups, respectively (p = 0.049). The most frequently used doses of C/T were 1.5 g IV q8h while undergoing continuous venovenous hemodiafiltration and 0.75 g IV q8h while undergoing hemodialysis (p = 0.209). The median duration of therapy was 9 (4.5 - 13) days in the clinically cured group vs. 5 (3.75 - 5.5) days in those who had clinical failure (p = 0.038). There was no adverse event reported using these doses during the study period. CONCLUSION: The used doses of C/T in this study were higher than those approved by the U.S. FDA, while clinical success is uncertain. Larger outcomes and pharmacokinetics studies are needed to establish effective dosing and therapy duration.

A Case of Hemorrhagic Cholecystitis in a Patient on Apixaban After COVID-19 Infection.

BACKGROUND Hemorrhagic cholecystitis is a rare cause of abdominal pain, which can result from malignancy, bleeding, or trauma. The presentation, which includes right upper-quadrant pain, nausea, and vomiting, can overlap with other disease states, thereby rendering the diagnosis challenging. CASE REPORT We describe a patient taking apixaban wo had paroxysmal atrial fibrillation with history of joint pain on long-term steroids who developed hemorrhagic cholecystitis following an episode of pneumonia secondary to SARS-CoV-2 virus (COVID-19) infection. The hospital COVID-19 pneumonia protocol included the administration of steroids and symptomatic care. Following discharge, he presented to our hospital with a sudden onset of severe abdominal pain and distention accompanied by elevated liver enzymes and a low hemoglobin level of 78 g/L. Magnetic resonance cholangiopancreatography revealed a distended gallbladder and intraluminal layering, early subacute blood products, and increased wall thickness, which was thought to represent non-calcular hemorrhagic cholecystitis. Furthermore, a stable 18×16×20 mm cyst in the tail of the pancreas was also located posteriorly, with indentation to the splenic vein. The patient was managed conservatively, and the pain subsided on day 3 after admission. CONCLUSIONS Hemorrhagic cholecystitis is rarely reported with the use of the direct oral anticoagulants (DOACs). In our case the combination of a recent COVID-19 hospitalization, steroid use, and possible pancreatic cancer (CA 19-9 288.4 kU/L) may have contributed to such incidence in the setting of apixaban utilization; however, it is not possible to make definitive correlations. Investigating hemorrhagic cholecystitis in the setting of DOAC use in patients with multiple risk factors such as those that existed in our patient is imperative for proper diagnosis and management.

Sustaining Life versus Altering Life-Saving Drugs: Insights to Explain the Paradoxical Effect of Extracorporeal Membrane Oxygenation on Drugs.

There has been a substantial increase in the use of extracorporeal membrane oxygenation (ECMO) support in critically ill adults. Understanding the complex changes that could affect drugs' pharmacokinetics (PK) and pharmacodynamics (PD) is of suitable need. Therefore, critically ill patients on ECMO represent a challenging clinical situation to manage pharmacotherapy. Thus, clinicians' ability to predict PK and PD alterations within this complex clinical context is fundamental to ensure further optimal and, sometimes, individualized therapeutic plans that balance clinical outcomes with the minimum drug adverse events. Although ECMO remains an irreplaceable extracorporeal technology, and despite the resurgence in its use for respiratory and cardiac failures, especially in the era of the COVID-19 pandemic, scarce data exist on both its effect on the most commonly used drugs and their relative management to achieve the best therapeutic outcomes. The goal of this review is to provide key information about some evidence-based PK alterations of the drugs used in an ECMO setting and their monitoring.

Microbiologic outcomes of ceftazidime-avibactam dosing in patients with sepsis utilizing renal replacement therapies.

INTRODUCTION: The suggested dose of ceftazidime-avibactam (CEF/AVI) in patient with multidrug resistant organisms and utilizing renal replacement therapies (RRTs) is not validated in clinical studies. The objective of this study was to evaluate the microbiologic cure of bacteremia and pneumonia using the recommended CEF/AVI dosing in patients utilizing RRT. METHODS: A retrospective observational study conducted at our institution between September 15, 2018 and March 15, 2022. The primary end point was to determine the microbiologic cure. The secondary end points were the clinical cure, 30-day recurrence, 30-day all cause mortality. RESULTS: Fifty-six patients met the inclusion criteria, 36 (64.3%) were males, the median age was 69 (59.5-79.3) years, and the median weight was 69 (60-83.8) kg. Pneumonia represented 34 (60.7%) of infections. Microbiologic cure was achieved in 32 (57%) subjects. However, clinical cure was achieved in 23 (71.9%) patients in the microbiologic cure group versus 12 (50%) in the microbiologic failure group (p = 0.094). The 30-day recurrence occurred in 2 (6.3%) patients in the microbiologic cure group versus 3 (12.5%) in the microbiologic failure group (p = 0.673). Further, the 30-day all-cause mortality was 18 (56.3%) versus 10 (41.7%) in both groups respectively (p = 0.28). The most used dose in patients utilizing continuous veno-venous hemofiltration (CVVH) was 1.25 g q8h, while the dose was 1.25 g q24h in those who utilized intermittent hemodialysis (IHD). The multivariate logistic regression indicated that bacteremia (OR 41.5 [3.77-46]), Enterobacterales (OR 5.4 [1.04-27.9]), and the drug daily dose (OR 2.33 [1.15-4.72]) were independently associated with microbiologic cure. CONCLUSION: Microbiologic cure of ceftazidime-avibactam in patient utilizing CVVH and IHD is dependent on bacteremia diagnosis, the drug daily dose, and bacterial species. These findings need to be replicated in a larger prospective study, with no recommendations in those utilizing RRT.

Urinary tract infections in hemodialysis patients-The controversy of antimicrobial drug urine concentrations.

BACKGROUND: Major infectious diseases societies recommend the use of antimicrobials that achieve high-urinary concentrations to treat urinary tract infection (UTI), which is a concept of little relevance to the oliguric and anuric hemodialysis (HD) dependent population. Outcome studies in this population are more relevant, but unfortunately scarce. We sought to investigate the impact of different antimicrobials on clinical and microbiologic outcomes in HD dependent population. METHODS: A retrospective observational study conducted at our quaternary care hospital between May 2015 and December 2019. We included all HD dependent adults diagnosed with UTIs. Our primary end points were clinical and microbiologic cure. Our secondary end points were 90-day recurrence and mortality. RESULTS: Fifty-six patients were included in the study with 33 (58.9%) females, mean age of 69.9 ± 11.6 years, and mean body mass index of 27.7 ± 7.8 kg/m2 . Thirty-six subjects of the sample (64.3%) were anuric. Ninety-one percent of the patients achieved clinical cure. Out of those who had repeat cultures, 90.7% achieved microbiologic cure. Clinical and microbiologic cure rates were not significantly different between the oliguric and anuric groups. The 90-day recurrence rate was 11.1% and mortality was 19%, none of them was related to UTI. CONCLUSION: Our findings demonstrate high rate of clinical and microbiologic cure in the treatment of oliguric and anuric HD dependent patients. We suggest that drug development and treatment societies to consider clinical and microbiologic outcomes in conjunction with achievable urinary concentration when making recommendations for the treatment of UTI.

Pharmacy Practice Standards for Outpatient Nephrology Settings.

Patients with kidney disease represent a medically complex group of patients with high medication burdens that could benefit from clinical pharmacy services as part of the interdisciplinary care team to optimize medication use. The "Advancing American Kidney Health" executive order includes new value-based reimbursement models to be tested by the Center for Medicare and Medicaid Innovation beginning January 2021 and January 2022. Advancing American Kidney Health executive order poses opportunities for the inclusion of comprehensive medication management. Following an iterative process integrating input from a diverse expert panel, published standards, clinical practice guidelines, peer review, and stakeholder feedback, our group developed practice standards for pharmacists caring for patients with kidney disease in health care settings. The standards focus on activities that are part of direct patient care and also include activities related to public health and advocacy, population health, leadership and management, and teaching, education and dissemination of knowledge. These standards are intended to be used by a variety of professionals, from pharmacists starting new practices to practice managers looking to add a pharmacist to the clinical team, to create standardization in services provided.

Is Cefoxitin a Carbapenem Sparing Agent in the Management of Urinary Tract Infections Caused by ESBL Producing Enterobacterales?

Background: Cefoxitin has shown in vitro activity against Extended-Spectrum ß-Lactamase (ESBL) producing Enterobacterales. Outcome data regarding cefoxitin as a carbapenem sparing agent in the management of urinary tract infections (UTI) are scarce. We sought to evaluate the clinical and microbiologic efficacy of cefoxitin as compared to ertapenem. Methods: A retrospective observational study was conducted at our quaternary care institution between May 2015 and March 2019. We identified all patients who received cefoxitin for the treatment of UTI during the study period and used Charlson Comorbidity Index to select a matching cohort from patients who received ertapenem. Primary end points were clinical and microbiological cure. Results: Thirty patients who received cefoxitin were matched with 55 patients who received ertapenem. Clinical cure was marginally in favor of ertapenem: 83.2% in cefoxitin group versus 96.8% in ertapenem group (P = .042). However, 90-day recurrence was in favor of cefoxitin: 13.5% in cefoxitin group versus 34.8% in ertapenem group (P = .045). Microbiologic cure was not significant between the 2 groups with 88.6% success in cefoxitin versus 100% in ertapenem. Additionally, the group difference on 30-day recurrence or relapse rates and the 90-day mortality rate were not clinically significant. Conclusion: Cefoxitin achieved similar microbiologic cure rate when compared to ertapenem for the treatment of UTI caused by ESBL-producing Enterobacterales. No significant differences were found in 30-day recurrence/relapse or mortality rates. Larger randomized controlled trials are required to identify the clinical sittings in which cefoxitin could be used as a carbapenem-sparing agent in the treatment of UTI.

Assessment of antibiotic appropriateness at discharge: experience from a quaternary care hospital setting.

Background: There is a gap in antimicrobial stewardship in transitions of care. Objectives: To assess the appropriateness of antibiotics utilized and prescribing habits at hospital discharge. Methods: A retrospective, observational study was conducted at our quaternary care hospital between January 2021 and March 2021. During the study period, all patients discharged on antibiotics for pneumonia (PNA), skin and soft tissue infections (SSTI), urinary tract infections (UTI) and intra-abdominal infections (IAI) were included. The overall appropriateness of therapy was assessed based on the following combined criteria: agent, dose, frequency, duration of therapy, and ability to meet diagnostic criteria. Results: One hundred and forty-five subjects met the inclusion criteria. Of these, 44 (30.3%) were determined to have received overall appropriate antibiotic therapy. The most common infections were UTI, followed by IAI, PNA, and SSTI, respectively. Further, from the group deemed to have received overall inappropriate therapy, 26 of the 101 (25.7%) patients received an inappropriate antibiotic choice, 6 (5.9%) an inappropriate dose, and 84 (83.2%) an inappropriate duration of therapy. Conclusions: Inappropriate duration of therapy represented the most challenging problem with antibiotic regimens at discharge. Larger studies are needed to identify potential interventions that are effective, and can be implemented in all settings, including resource-limited ones.

Outcomes of caspofungin use in the treatment of Candida-related urinary tract infections, a case series.

Echinocandins are generally excluded in the treatment of Candida-related urinary tract infections due to their poor urinary concentration. In the presence of fluconazole resistant Candida species, such as C. Glabrata and C. auris, alternative therapies are needed. We herein report the use of caspofungin for the treatment of 10 patients with candiduria, including C. auris. Mycological cure was achieved in 6 of 7 patients and clinical cure was achieved in 8 of 10 patients. Larger studies are needed to confirm our findings.

Tocilizumab and COVID-19: Timing of Administration and Efficacy.

Elevated concentrations of interleukin-6 have been demonstrated to be an important key factor in COVID-19 host immune impairment. It represents an important prognostic factor of harm associated with COVID-19 infection by stimulating a vigorous proinflammatory response, leading to the so-called "cytokine storm". Therefore, immunomodulatory interventions targeting interleukin-6 receptor antagonism have been investigated as potential treatments to counterbalance the host immune dysregulation and to support the advantageous effects of corticosteroids. Tocilizumab is a recombinant humanized monoclonal antibody that has gained much interest during the COVID-19 pandemic as an interleukin-6 receptor antagonist. Various early observational studies have reported beneficial effects of tocilizumab. Moreover, consequent randomized controlled trials have subsequently shown significant positive results about tocilizumab efficacy and safety, focusing on outcomes like mortality, risk of intensive care unit admission, and the need for mechanical ventilation, while others presented conflicting findings. In this review, we first described the pathophysiology of COVID-19 infection while highlighting the role of interleukin-6. Furthermore, we also discussed the non-conclusive evidence about tocilizumab to be used as the standard of care therapy for all patients with COVID-19 pneumonia, as well as its beneficial effects in selected patients.

QT Prolongation in Critically Ill Patients With SARS-CoV-2 Infection.

BACKGROUND: Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population. METHODS: We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms). RESULTS: Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], P < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], P = .04), and male gender (95% vs. 82.8%, P = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation (P = .004 for the likelihood-ratio test). CONCLUSION: The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.

Hypertriglyceridemia in Critically Ill Patients With SARS-CoV-2 Infection.

BACKGROUND: Patients with SARS-CoV-2 infection could develop severe disease requiring critical care admission. Case reports indicated high incidence of hypertriglyceridemia (HTG) in critically ill patients infected with SARS-CoV-2, which might be related to the drugs. OBJECTIVE: We sought to determine the risk factors associated with HTG in this population and to investigate the relationship between HTG and lipase. METHODS: A retrospective observational study was conducted at our hospital between March 1 and June 30, 2020. Patients were included if they were ≥18 years old, admitted to the intensive care unit (ICU), tested positive for SARS-CoV-2, and had triglycerides (TG) checked during their hospital stay. RESULTS: Of the 111 critically ill patients, 103 patients were included. Males comprised 88.3% of the sample. The median TG at baseline was 197.4 (IQR: 139.8-283) mg/dL. The lipase median level at baseline was 23.00 (IQR: 0.00-69.50) IU/L. The results of the mixed-effects logistic regression analysis indicated that patient-level variables, favipiravir use, blood glucose level, and propofol use were significantly associated with HTG. There was no relationship between lipase and TG levels over time. Furthermore, TG concentrations over time showed a similar trend to inflammatory markers. CONCLUSION AND RELEVANCE: The incidence of clinically significant HTG was high and was associated with propofol and favipiravir use. HTG might reflect the high inflammatory state in these patients. Clinicians should look at the full picture before changing therapies based only on HTG. Our findings need to be replicated in a larger prospective study.

Clinical Pharmacokinetics and Pharmacodynamics of Desmoteplase.

Desmoteplase is a bat (Desmodus rotundus) saliva-derived fibrinolytic enzyme resembling a urokinase and tissue plasminogen activator. It is highly dependent on fibrin and has some neuroprotective attributes. Intravenous administration of desmoteplase is safe and well tolerated in healthy subjects. Plasma fibrinolytic activity is linearly related to its blood concentration, its terminal elimination half-life ranges from 3.8 to 4.92 h (50 vs. 90 µg/kg dose). Administration of desmoteplase leads to transitory derangement of fibrinogen, D-dimer, alpha2-antiplasmin, and plasmin and antiplasmin complex which normalize within 4-12 h. It does not alter a prothrombin test, international normalized ratio, activated partial thromboplastin time, and prothrombin fragment 1.2. Desmoteplase was tested in myocardial infarction and pulmonary embolism and showed promising results versus alteplase. In ischemic stroke trials, desmoteplase was linked to increased rates of symptomatic intracranial hemorrhages and case fatality. However, data from "The desmoteplase in Acute Ischemic Stroke" Trials, DIAS-3 and DIAS-J, suggest that the drug is well tolerated and its safety profile is comparable to placebo. Desmoteplase is theoretically a superior thrombolytic because of high fibrin specificity, no activation of beta-amyloid, and lack of neurotoxicity. It was associated with better outcomes in patients with significant stenosis or occlusion of a proximal precerebral vessels. However, DIAS-4 was stopped as it might have not reached its primary endpoint. Due to its promising properties, desmoteplase may be added into treatment of ischemic stroke with extension of the time window and special emphasis on patients presenting outside the 4.5-h thrombolysis window, with wake-up strokes and strokes of unknown onset.

Practical considerations for vancomycin dosing in hemodialysis patients: Perspectives from the nephrology stewardship pharmacist.

BACKGROUND: Vancomycin remains the principal antibiotic used to treat methicillin-resistant Staphylococcus aureus in patients with chronic kidney disease stage 5 utilizing hemodialysis (CKD-5D). The recent guidelines have added comprehensive dosing guidance to assist clinicians optimize vancomycin dosing in this population. The purpose of this review was to elaborate on additional practical and stewardship considerations which clinicians may apply in this unique patient population. MATERIALS AND METHODS: Relevant clinical outcome and clinical pharmacokinetic (PK) studies were discussed in this review since the publication of the 2009 version of the vancomycin therapy guidelines. Administering vancomycin during the last 60 - 90 minutes of hemodialysis is preferred to prevent vascular damage and preserve patients' vascular access. RESULTS: All published and pertinent data were included across the study period. Two outcome studies, 13 clinical PK studies, and 2 PK modeling studies were identified and discussed in this review. The used loading doses (LD) in the reviewed studies ranged between 18 and 23 mg/kg (~ 1.5 - 2 g) followed by a maintenance dose (MD) of 8 - 13 mg/kg (~ 1 g) administered in the last hour of dialysis (high flux). This dosing strategy resulted in vancomycin pre-dialysis concentrations of ≥ 13 mg/L and favorable clinical outcomes, particularly in patients with bacteremia and skin and soft tissue infections. Regardless of how high the pre-HD vancomycin concentrations were, vancomycin was not associated with favorable outcomes in patients with deep-seated infections. CONCLUSION: Vancomycin administration using dialysis access in the last hour of dialysis is suggested. Administering a standard MD would simplify dosing and reduce the risk of errors. Vancomycin dosing is challenging in this patient population.

Risk Factors for Recurrence of Clostridioides difficile in Hospitalized Patients.

BACKGROUND: Diarrhea and pseudomembranous colitis associated with Clostridioides difficile - a spore-forming anaerobic Gram-positive bacillus - is a major infection in hospitalized patients with a profound impact on clinical and economic outcomes. Recurrence (rCDI) is common and predisposes to further episodes with poor outcomes. METHOD: We aimed to identify a wide range of risk factors for recurrence to guide stewardship initiatives. After ethical approval, we commenced collecting demographic and clinical data of patients older than 18 years with clinically and microbiologically confirmed C. difficile infection. Data were statistically analyzed using R software. RESULTS: Of 204 patients included in the analysis, 36 (18%) suffered 90-day recurrence, rCDI was higher among females (23%) compared to males (13%), overall age median (IQR) was 66 (51-77), and for rCDI cases 81 (69-86) years. Among 26 variables analyzed to evaluate their association with rCDI, prior clindamycin exposure, concurrent use of aztreonam, patients >76 years, total hospital length of stay, and LOS before diagnosis ≤7 days, WBC ≤ 9.85 × 103 at discharge were more likely to experience rCDI. CONCLUSION: As identified in this analysis, patients with risk factors for rCDI could be candidates for close monitoring, a high index of suspicion, and risk mitigation interventions to avoid rCDI and improve clinical outcomes.

Acinetobacter baumannii Infections in Hospitalized Patients, Treatment Outcomes.

Background Acinetobacter baumannii (AB), an opportunistic pathogen, could develop into serious infections with high mortality and financial burden. The debate surrounding the selection of effective antibiotic treatment necessitates studies to define the optimal approach. This study aims to compare the clinical outcomes of commonly used treatment regimens in hospitalized patients with AB infections to guide stewardship efforts. Material and methods: Ethical approval was obtained, 320 adult patients with confirmed AB infections admitted to our tertiary care facility within two years were enrolled. The treatment outcomes were statistically analyzed to study the relation between antibiotic regimens and 14, 28, and 90-day mortality as the primary outcomes using binary logistic regression-using R software-in addition to the length of hospitalization, adverse events due to antibiotic treatment, and 90-day recurrence as secondary outcomes. Results: Among 320 patients, 142 (44%) had respiratory tract, 105 (33%) soft tissue, 42 (13%) urinary tract, 22 (7%) bacte iemia, and other infections 9 (3%). Nosocomial infections were 190 (59%) versus community-acquired. Monotherapy was significantly associated with lower 28-day (p < 0.05, OR:0.6] and 90-day (p < 0.05, OR:0.4) mortality rates, shorter length of stay LOS (p < 0.05, Median: -12 days] and limited development of adverse events (p < 0.05, OR:0.4). Subgroup analysis revealed similar results ranging from lower odds of mortality, adverse events, and shorter LOS to statistically significant correlation to monotherapy. Meropenem (MEM) and piperacillin/tazobactam (PIP/TAZ) monotherapies showed non-significant high odd ratios of mortalities, adverse events, and disparate LOS. There was a statistical correlation between most combined therapies and adverse events, and longer LOS. Colistin based and colistin/meropenem (CST/MEM) combinations were superior in terms of 14-day mortality (p = 0.05, OR:0.4) and (p < 0.05, OR:0.4) respectively. Pip/Taz and MEM-based combined therapies were associated with statistically non-significant high odd ratios of mortalities. Tigecycline (TGC)-based combinations showed a significant correlation to mortalities (p < 0.05, OR:2.5). Conclusion: Monotherapy was associated with lower mortality rates, shorter LOS, and limited development of adverse events compared to combined therapies. Colistin monotherapy, colistin/meropenem, and other colistin combinations showed almost equivalent mortality outcomes. Patients on combined therapy were more susceptible to adverse events and comparable LOS. The possible adverse outcomes of PIP/TAZ and MEM-based therapies in the treatment of MDRAB infections and the association of TGC with a higher mortality rate raise doubts about their treatment role.