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.

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.

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.

Ertapenem Neurotoxicity in Hemodialysis Patients-Safe and Effective Dosing Is Still Needed: A Retrospective Study and Literature Review.

BACKGROUND: The approved dosing of ertapenem in patients with chronic kidney disease stage 5 utilizing dialysis (CKD-5D) is 0.5 g intravenous daily. Several reports associated this dosing strategy with neurotoxicity. OBJECTIVE: The purpose of this study is to identify the incidence of neurotoxicity in this population and the risk factors associated with this toxicity. The secondary objective was to review the literature and discuss a safer/cost-effective dosing strategy based on available data. METHODS: A retrospective study was conducted screening all patients who received ertapenem and hemodialysis at our quaternary hospital between May 2015 and March 2019. Patients' demographics, comorbidities, concomitant drugs (known to induce neurotoxicity), and seizure history were collected. RESULTS: A total of 99 eligible patients were identified; 10 of them (10%) developed neurotoxicity. The patients who developed neurotoxicity were all male; mean age was 74 ± 9 years as compared with 68.9 ± 13 years in the sample. Bivariate relationships between all predictors and the seizures (dichotomously coded) were estimated to investigate the risk factors. The following were the significant predictors of seizures: male sex (17%; P = 0.014), dementia (27%; P = 0.012), and concomitant use of ß-lactams, aminoglycosides, or fluoroquinolones (19.6%; P = 0.042). CONCLUSION AND RELEVANCE: The currently approved ertapenem dose imposes a risk of developing neurotoxicity in patients with CKD-5D. Utilizing the published data in this population, alternative post-dialysis dosing strategies administered through dialysis access such as 1 g loading dose, followed by either 0.5 g (for the 48 hours interdialytic time) or 1 g (for the 72 hours interdialytic time) might warrant further investigation for efficacy and safety.

Role of nephrology pharmacists in the management of anemia in outpatient dialysis units: A Canadian model
.

INTRODUCTION: Hemodialysis patients frequently suffer from anemia. Proper utilization of therapies such as iron and erythropoiesis-stimulating agents (ESAs) is crucial to attain symptom management and established hemoglobin targets. The purpose of this study was to evaluate the clinical and financial impact of nephrology-trained pharmacists on anemia management in these patients. MATERIALS AND METHODS: A retrospective study of outpatient hemodialysis patients observed between January 2010 and December 2011. In December 2010, pharmacists were tasked to manage anemia under a medical directive. Primary endpoints were compared across years using a mixed-effects model strategy. An unstructured random effects correlation matrix was utilized to capture patient-level variation in 2010 and 2011, separately. RESULTS: Of 202 patients identified, 163 contributed in both years, 57% were males, aged 65.18 ± 16.3 years. Hemoglobin levels were 10.95 ± 0.95 and 10.83 ± 0.94 g/dL in 2010 vs. 2011, respectively (p = 0.158), while the transfusion rate was 1.3% and 1.8%, respectively (p = 0.196). Ferritin levels of 273.5 ± 22 and 317.1 ± 12 ng/mL (p = 0.0019), iron saturation 0.30 ± 0.11 and 0.30 ± 0.05 (p = 0.838), and parenteral iron dose of 215.4 ± 100.2 and 317.1 ± 123.7 mg, respectively (p = 0.996), were identified. Finally, the average weekly ESA dose in 2010 was higher and trending up as compared to 2011 where it significantly trended down. The amount of intravenous erythropoietin alfa was 12,315.6 ± 76 vs. 11,364.1 ± 52 units/week, respectively (p = 0.0556) with expenditure of 2.8 million Canadian dollars in 2010 vs. 2.3 million Canadian dollars in 2011. CONCLUSION: The participation of a nephrology pharmacist resulted in favorable outcomes in dose optimization, decreased expenditure, and positive trends in therapeutic goal achievement.

Humanized Exposures of Cefiderocol, a Siderophore Cephalosporin, Display Sustained in vivo Activity against Siderophore-Resistant Pseudomonas aeruginosa.

We evaluated the in vivo efficacy of humanized exposures of cefiderocol, a novel siderophore cephalosporin, against a test panel of P. aeruginosa (PSA) previously shown to develop resistance to 2 preclinical candidate siderophores (MB-1 and SMC-3176). In the thigh infection model, the PSA bacterial density in untreated controls grew from 5.54 ± 0.23 to 8.68 ± 0.57 log10 CFU over 24 h. The humanized cefiderocol exposure resulted in >1 log10 CFU reduction in all 8 isolates, while MB-1 and SMC-3176 exhibited variable activity similar to that previously reported. Humanized exposures of cefepime and levofloxacin, acting as positive antimicrobial controls displayed activity consistent with that of the bacterial phenotypic susceptibility profiles. Cefiderocol manifested in vivo efficacy against all PSA isolates including those resistant to cefepime and levofloxacin in contrast to its predecessor siderophore compounds. These preclinical data are supportive of further evaluation of cefiderocol in the treatment of P. aeruginosa.

Anti-staphylococcal activity resulting from epithelial lining fluid (ELF) concentrations of amikacin inhale administered via the pulmonary drug delivery system.

BACKGROUND: Amikacin inhale (BAY41-6551), a unique drug-device combination of a specially formulated drug solution and a pulmonary drug delivery system device (AMK-I) is currently under phase III study as an adjunctive therapy to IV antibiotics for the treatment of Gram-negative pneumonia in mechanically ventilated patients. While the epidemiology of nosocomial pneumonia is predominated by Gram-negative pathogens such as Pseudomonas aeruginosa and the Enterobacteriaceae, Staphylococcus aureus is increasingly recognized as a pathogen of concern for these pulmonary based infections. Since the aminoglycosides are historically quite active against S. aureus the use of adjunctive AMK-I may enhance bacterial eradication. Herein, we aimed to characterize the in vitro pharmacodynamic (PD) profile of human-simulated ELF exposures of AMK-I against both methicillin-sensitive (MSSA) and -resistant (MRSA) S. aureus. METHODS: An in vitro model was used to simulate the resultant ELF pharmacokinetic profile of amikacin after the administration of AMK-I 400 mg q12h. The antibacterial activity of this regimen was tested against 7 S. aureus isolates that display MIC profiles encountered clinically (4 MRSA; MIC range 4-64, 3 MSSA; MIC range 8-16 mg/L). Experiments were conducted over 24 h and samples were taken throughout this period to assess the bacterial density in both control and treatments. RESULTS: The mean ± SD inoculum 0 h bacterial density was 6.4 ± 0.09 which increased to 8.6 ± 0.19 log10 CFU/mL in the control models by the end of 24 h experiments. Simulated ELF concentrations of AMK-I resulted in a rapid, 5 log10 declined in CFU over the initial 12 h for all MRSA and MSSA isolates. After 12 h, all bacterial counts remained below the limit of detection (LOD, 1.7 log10 CFU/mL) and no regrowth was evident at the end of the study. CONCLUSION: AMK-I produced an ELF exposure profile that was rapidly bactericidal against S. aureus displaying typical MICs to amikacin irrespective of their phenotypic profile to methicillin. While the Gram-negative organisms are the target pathogens for AMK-I in the ongoing clinical trials, these data suggest that this adjunctive regimen may also have the potential to eradicate both MSSA and MRSA from lower airway which needs to be further evaluated in randomized-controlled clinical trials.

Efficacy of humanized high-dose meropenem, cefepime, and levofloxacin against Enterobacteriaceae isolates producing Verona integron-encoded metallo-ß-lactamase (VIM) in a murine thigh infection model.

We aimed to describe the in vivo activity of humanized pharmacokinetic exposures of meropenem and comparators against Verona integron-encoded metallo-ß-lactamase (MBL) (VIM)-producing Enterobacteriaceae in a murine model. Levofloxacin activity was predicted by its MIC, and cefepime activity displayed variability, whereas meropenem produced a >1 log CFU reduction against all isolates despite high MICs indicative of resistance. Our results suggest that despite in vitro resistance, high-dose meropenem may be a possible option against infections caused by Enterobacteriaceae producing MBL-type carbapenemases.

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 Ceftazidime-Avibactam versus Ceftolozane-Tazobactam in Managing Pseudomonal Infections in Patients Undergoing Renal Replacement Therapy.

The optimal doses of ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T) for treating multidrug-resistant (MDR) Pseudomonas aeruginosa (PSA) in patients utilizing renal replacement therapy (RRT) are not well established. Hence, the objective of this study is to evaluate the clinical outcomes associated with the suggested doses of CZA and C/T in patients with PSA infection utilizing RRT. METHODS: This is a retrospective study conducted at our hospital between September 2018 and March 2022. Clinical cure was the primary endpoint, while microbiologic cure, 30-day recurrence, and 30-day mortality were the secondary endpoints. RESULTS: In total, 45 subjects met the inclusion criteria, with 25 receiving CZA and 20 receiving C/T. The median age was 69 (52-81) and 69 (61.5-83) years, respectively, while the median weight was 70 (55.5-81.5) and 66 (57-79) kg, respectively. Clinical cure was achieved in 12 (48%) subjects in the CZA group and 12 (60%) in the C/T group (p = 0.432). Of the 36 subjects who had repeated cultures, a microbiologic cure was achieved in 14/23 (60%) subjects and 10/13 (76.9%) subjects (p = 0.273). Thirty-day recurrence was reported in 3 (12%) cases in the CZA group and 6 (30%) in the C/T group (p = 0.082). The 30-day mortality was 13 (52%) subjects in the CZA group and 10 (50%) in the C/T group (p = 0.894). The median maintenance dose of CZA was 1.88 (0.94-3.75) g and 2.25 (1.5-2.25) g for C/T. Multivariate logistic regression analysis indicated that both drugs did not differ significantly in clinical cure. Bloodstream infection (BSI) (OR = 25, 95% CI: 1.63-411.7, p = 0.021) was the only independent factor associated with clinical cure in this population. CONCLUSIONS: Our findings indicated that C/T and CZA did not significantly differ in achieving clinical cure in patients with MDR PSA infections undergoing RRT. Larger clinical trials are needed to confirm our findings.

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.

Infections in Glucose-6-Phosphate Dehydrogenase G6PD-Deficient Patients; Predictors for Infection-Related Mortalities and Treatment Outcomes.

Disturbances in the count or maturity of blood cells weaken their microbial defensive capacity and render them more susceptible to infections. Glucose-6-phosphate deficient patients are affected by a genetic disease that affects cell integrity with increased liability to infections and death. We aimed to investigate the risk factors for infection mortality in this patient population. We retrospectively examined the records of G6PD adult patients with confirmed infections and collected data related to demographics, infections (pathogens, types, and treatment regimens) in addition to mortality and length of stay outcomes. Data were statistically analyzed using R Programming language to identify contributing factors to mortality and treatment regimens association with outcomes. Records of 202 unique patients over 5 years were included, corresponding to 379 microbiologically and clinically confirmed infections. Patients > 60 years [p = 0.001, OR: 5.6], number of comorbidities 4 (2-5) [p < 0.001, OR: 1.8], patients needed blood transfusion [p = 0.003, OR: 4.3]. Respiratory tract infections [p = 0.037, OR: 2.28], HAIs [p = 0.002, OR: 3.9], polymicrobial infections [p = 0.001, OR: 10.9], and concurrent infection Gram-negative [p < 0.001, OR: 7.1] were significant contributors to 28-day mortality. The history of exposure to many antimicrobial classes contributed significantly to deaths, including ß-lactam/ß-lactamase [p = 0.002, OR: 2.5], macrolides [p = 0.001, OR: 3.34], and ß-lactams [p = 0.012, OR: 2.0]. G6PD patients are a unique population that is more vulnerable to infections. Prompt and appropriate antimicrobial therapy is warranted to combat infections. A strict application of stewardship principles (disinfection, shortening the length of stay, and controlling comorbid conditions) may be beneficial for this population. Finally, awareness of the special needs of this patient group may improve treatment outcomes.

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.

Infections in G6PD-Deficient Hospitalized Patients-Prevalence, Risk Factors, and Related Mortality.

G6PD deficiency is a genetic disease that weakens the immune system and renders affected individuals susceptible to infections. In the Sultanate of Oman resides a high number of recorded G6PD cases due to widespread consanguineous marriage, which may reach 25% of the population. We studied the infection patterns and risk factors for mortality to provide antimicrobial stewardship recommendations for these patients. After obtaining ethical approval, a registry of recorded cases was consulted retrospectively to include G6PD-deficient adult patients admitted to Suhar hospital over 5 years with microbiologically confirmed infections. Patient demographics, health-related information, infection causes, treatment, and clinical outcomes were studied. Data were analyzed to describe infection patterns and risk factors. Several variables, including underlying comorbidities and hospitalization details, such as length of stay, admission to critical care unit, blood transfusion, or exposure to an invasive procedure, were statistically associated with the acquisition of multidrug-resistant and hospital-acquired infections. Meanwhile, these infections were associated with a high mortality rate (28%), significantly associated with the patient's health status and earlier exposure to antimicrobial treatment due to previous bacterial infection. The high prevalence of G6PD deficiency among the Omani population should alert practitioners to take early action when dealing with such cases during infection that requires hospitalization. Strict infection control measures, Gram-negative empiric coverage, hospital discharge as early as possible, and potent targeted antimicrobial therapy in this patient population can ameliorate the treatment outcomes and should be emphasized by the antimicrobial stewardship team.

Acinetobacter baumannii Infection-Related Mortality in Hospitalized Patients: Risk Factors and Potential Targets for Clinical and Antimicrobial Stewardship Interventions.

Due to resistance and scarcity of treatment options, nosocomial Acinetobacter baumannii infections are associated with significant fatality rates. We investigated the factors contributing to infection-related deaths to develop tailored stewardship interventions that could reduce these high mortality rates. We reviewed the medical records of adult inpatients with A. baumannii infections over two years. Patient demographics and clinical data were collected and statistically analyzed. The study included 321 patients with positive A. baumannii microbiological cultures, with respiratory infections accounting for 58.6%, soft tissues 29.3%, bacteremia 8.6%, urine 2.1%, and others 1.4%. The study population's median (IQR) age was 62.6 (38.9−94.9) years, and hospital stay was 20 (9.5−40) days. Statistical analysis revealed that various risk factors contribute significantly to high in-hospital all-cause mortality (44%), as well as 14-day and 28-day mortality rates. Deaths increased by a factor of 1.04 with every additional year of age (p = 0.000), admission to the critical care unit (p = 0.000, OR: 2.86), and patients admitted with an infectious diagnosis had nearly three times the mortality rate as those admitted with other diagnoses (p = 0.000, OR: 3.12). Male gender (p < 0.001, OR: 2.14), any comorbid conditions (p = 0.000, OR: 5.29), prolonged hospitalization (>7 days) (p = 0.023, OR: 1.98), and hospital acquisition of infection (p = 0.027, OR: 1.68) were among the most significant predictors of mortality. All variables were investigated for their impact on all-cause, 14-day, and 28-day mortality rates. Improving multidisciplinary infection control practices, regular disinfection of patient care equipment, and optimal intubation practice that avoids unnecessary intubation are necessary interventions to reduce infection-related mortality rates. Better antibiotic selection and de-escalation, shorter hospital stays whenever possible, prompt medical stabilization of comorbid conditions, and fewer unnecessary admissions to critical care units will all lead to improved outcomes.

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.

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.

Optimal vancomycin dose in the treatment of Clostridium difficile infection, antimicrobial stewardship initiative.

C. difficile infections (CDI) are increasingly recognized as a leading cause of infectious diarrhea, with increasing morbidity and mortality. Treatment primarily centers around oral vancomycin treatment. A wide range of dosing regimens exist in clinical practice, with little evidence to help distinguish the therapeutic benefit between them. This is a retrospective cohort study conducted at an academic medical center that enrolled adult patients admitted with CDI. The primary outcome was a composite of complete or partial cure at the end of treatment and was assessed using a test of equivalency with a 20% equivalency limit. Subjects were divided into low dose (125 mg) or high dose (250 mg or 500 mg) of oral vancomycin dosed every 6 hours. Overall, 78 patients were included who received low dose vancomycin and 33 who received high dose. Generally, the two groups were similar, except the low dose group had significantly more leukocytosis and less ICU admission or hypotension compared to the high dose group. Equivalency between the two treatment groups was demonstrated (Absolute Risk Difference -0.022, 90% confidence interval: -0.13 to 0.18, p = 0.03). A stepwise logistic regression identified gender, baseline albumin, and ICU admission as significant predictors of the chance for complete or partial cure. No differences between groups for the secondary outcomes of 90-day readmission/recurrence, 30-day all-cause mortality, or time to resolution of diarrhea were demonstrated. Low dose oral vancomycin was demonstrated to result in equivalent outcomes compared to high dose vancomycin for the treatment of CDI.

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.

Treatment of recurrent urinary tract infections in anuric hemodialysis patient, do we really need antimicrobial urinary concentration?

Providing care for patients with chronic kidney disease requires considerations that are unique to this population. Several references recommend the treating urinary tract infections with antibiotics that achieve considerable concentrations in urine however this is not applicable in anuric patients undergoing hemodialysis who are unable to excrete antibiotics significantly in urine. We report successful treatment of several episodes of urinary tract infections in hemodialysis patient highlighting the questionable need for antimicrobial urine concentration.