Efficacy and safety of ertapenem dosing in patients with ESBL producing Enterobacterales infections utilizing renal replacement therapies.

PURPOSE: The clinical efficacy and safety of ertapenem use in patients undergoing renal replacement therapies (RRT) are not well-documented. Therefore, we aimed to investigate the safety and efficacy of ertapenem in patients with sepsis secondary to Enterobacterales who are undergoing RRT. METHODS: A retrospective cohort study was conducted on patients who met the inclusion criteria at our hospital between May 2015 and December 2021. The primary endpoint was 30-day mortality. Secondary endpoints included clinical cure, microbiologic cure, recurrence rate, and incidence of seizures. RESULTS: During the study period, 158 patients met the inclusion criteria. Of these, 86 were male (54.4%), the mean age was 66.4 ± 13.8 years, and the mean weight was 77 ± 22.4 kg. The most common diagnosis was bacteremia in 48 (30.4%) subjects, followed by urinary tract infection in 39 (24.7%) subjects, and pneumonia in 35 (22.2%) patients. The most isolated pathogens were Escherichia coli, followed by Klebsiella species. The median ertapenem dose was 0.5 g intravenously (IV) daily in those who received intermittent hemodialysis (IHD) and 1 g IV daily for those who received continuous veno-venous hemofiltration (CVVH). The 30-day mortality rate was 24%, the clinical cure rate was 89.2%, the microbiologic cure rate was 82%, the 30-day recurrence rate was 41.1%, and the incidence of seizures was 2.5%. Multivariate logistic regression analysis indicated that age (OR 1.04 [95% CI: 1.003-1.075]), being critically ill at therapy initiation (OR 2.9 [95% CI: 1.1-7.5]), and Enterobacterales other than Klebsiella species and Escherichia coli (OR 3.8 [95% CI: 1.1-12.5]) were significant independent risk factors associated with mortality in this population. Ertapenem dose was not associated with mortality. CONCLUSION: Our findings suggest that the commonly used doses of ertapenem in patients undergoing IHD and CVVH are clinically effective but may pose a higher risk of seizures. A comprehensive pharmacokinetic study is needed to determine the most effective and safe dose for this population.

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.

A Tangled Autoimmune Trio: Multiple Sclerosis, Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antineutrophil Cytoplasmic Antibody Vasculitis.

The coexistence of multiple autoimmune diseases in the same individual is unusual and has received little attention in the literature. We present a young female patient with multiple sclerosis, systemic lupus erythematosus, and biopsy-proven renal proteinase 3 antineutrophil cytoplasmic antibodyassociated vasculitis who responded well to intravenous rituximab clinically and serologically.

Refractory seizures in a dialysis patient and a vitamin consigned to oblivion.

Intradialytic breakthrough seizures refractory to multiple classes of antiepileptic medications are not common and can be due to many different reasons. Pyridoxine deficiency is an under-recognized cause of such seizures and frequently missed in clinical practice. Many factors specifically related to dialysis can lead to pyridoxine deficiency and in turn can contribute to refractory seizures. Herein, we report one of the very few cases of intradialytic breakthrough refractory seizures secondary to pyridoxine deficiency recognized in the literature.

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.

Bile acid nephropathy induced by anabolic steroids: A case report and review of the literature.

Bile acid nephropathy also known as cholemic nephropathy is a rare and overlooked form of acute kidney injury that occurs in the setting of severe hyperbilirubinemia. The exact etiology remains unknown, and there is a lack of treatment guidelines for this clinical condition. Anabolic steroids are known to cause hepatoxicity occasionally leading to acute kidney injury. We report the case of a 27-year-old male patient who developed bile acid nephropathy as a result of severe hyperbilirubinemia secondary to anabolic steroids-induced liver injury. He was conservatively managed. We review the current literature touching on the etiology, pathophysiology, diagnosis, and management of bile acid nephropathy in an attempt to shed light on this clinical condition, which may present as a diagnostic and therapeutic challenge.

Severe Acute Kidney Injury in Critically Ill Patients with COVID-19 Admitted to ICU: Incidence, Risk Factors, and Outcomes.

BACKGROUND: Critically ill patients with COVID-19 are prone to develop severe acute kidney injury (AKI), defined as KDIGO (Kidney Disease Improving Global Outcomes) stages 2 or 3. However, data are limited in these patients. We aimed to report the incidence, risk factors, and prognostic impact of severe AKI in critically ill patients with COVID-19 admitted to the intensive care unit (ICU) for acute respiratory failure. METHODS: A retrospective monocenter study including adult patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection admitted to the ICU for acute respiratory failure. The primary outcome was to identify the incidence and risk factors associated with severe AKI (KDIGO stages 2 or 3). RESULTS: Overall, 110 COVID-19 patients were admitted. Among them, 77 (70%) required invasive mechanical ventilation (IMV), 66 (60%) received vasopressor support, and 9 (8.2%) needed extracorporeal membrane oxygenation (ECMO). Severe AKI occurred in 50 patients (45.4%). In multivariable logistic regression analysis, severe AKI was independently associated with age (odds ratio (OR) = 1.08 (95% CI (confidence interval): 1.03-1.14), p = 0.003), IMV (OR = 33.44 (95% CI: 2.20-507.77), p = 0.011), creatinine level on admission (OR = 1.04 (95% CI: 1.008-1.065), p = 0.012), and ECMO (OR = 11.42 (95% CI: 1.95-66.70), p = 0.007). Inflammatory (interleukin-6, C-reactive protein, and ferritin) or thrombotic (D-dimer and fibrinogen) markers were not associated with severe AKI after adjustment for potential confounders. Severe AKI was independently associated with hospital mortality (OR = 29.73 (95% CI: 4.10-215.77), p = 0.001) and longer hospital length of stay (subhazard ratio = 0.26 (95% CI: 0.14-0.51), p < 0.001). At the time of hospital discharge, 74.1% of patients with severe AKI who were discharged alive from the hospital recovered normal or baseline renal function. CONCLUSION: Severe AKI was common in critically ill patients with COVID-19 and was not associated with inflammatory or thrombotic markers. Severe AKI was an independent risk factor of hospital mortality and hospital length of stay, and it should be rapidly recognized during SARS-CoV-2 infection.

International Medical Graduates in Nephrology: Roles, Rules, and Future Risks.

International medical graduates (IMGs) have become an increasingly essential part of many residency and fellowship programs in the United States. IMGs, who may be of either US or non-US citizenship, contribute significantly to the physician workforce across this country, particularly in underserved areas, as well as in their home countries on their return after training. Approximately 65% of nephrology fellows are IMGs, with most of these being non-US citizens. Non-US IMG applications for nephrology fellowship have been declining, exacerbating an ongoing shortage of nephrology trainees. IMGs face visa status restrictions and immigration policy concerns, limitations on federally funded research support, and difficulty finding desirable jobs in both private practices and academia after fellowship. We review training, examination, and licensure requirements, as well as visa status rules for IMGs. We also discuss the potential negative impact of recent immigration policies limiting the entry of non-US IMGs on the medical community in general and in nephrology in particular.

New-onset hepatitis C virus-associated glomerulonephritis following sustained virologic response with direct-acting antiviral therapy
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Glomerulonephritis (GN) is an important extra-hepatic manifestation of infection with hepatitis C virus (HCV). HCV-associated GN occurs due to HCV-induced lymphoproliferation, leading to the generation of pathogenic immune complexes, including complexes containing cryoglobulins. The management of HCV-associated extra-hepatic disease is focused on viral eradication, with direct-acting antiviral agents leading to high rates of sustained virologic remission. There have been a few reports of relapsing cryoglobulinemic vasculitis after sustained virologic remission was achieved with interferon-based therapies. This report presents two cases of new-onset HCV-associated GN that occurred after sustained virologic response was achieved with direct-acting antiviral (DAA) therapy.
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