Novel ß-lactam-ß-lactamase inhibitors as monotherapy versus combination for the treatment of drug-resistant Pseudomonas aeruginosa infections: A multicenter cohort study.

BACKGROUND: Data comparing the clinical outcomes of novel ß-lactam-ß-lactamase inhibitors given in combination versus monotherapy for the treatment of multidrug-resistant (MDR) P. aeruginosa infections are lacking. METHOD: This retrospective cohort study included patients who received novel ß-lactam-ß-lactamase inhibitors as monotherapy or in combination for the treatment of MDR P. aeruginosa infections. The study was conducted between 2017 and 2022 in 6 tertiary care hospitals in Saudi Arabia. Overall in-hospital mortality, 30-day mortality, clinical cure, and acute kidney injury (AKI) were compared between recipients of monotherapy versus combination using multivariate logistic regression analysis. RESULT: 118 patients and 82 patients were included in monotherapy and combination therapy arms, respectively. The cohort represented an ill population with 56% in the intensive care unit and 37% in septic shock. A total of 19% of patients presented with bacteremia. Compared to monotherapy, combination therapy did not significantly differ in clinical cure (57% vs. 68%; P = 0.313; OR, 0.63; 95% CI, 0.36-1.14) in-hospital mortality (45% vs. 37%; P = 0.267; OR, 1.38; 95% CI, 0.78-2.45), or 30-day mortality (27% vs. 24%; P = 0.619; OR, 1.18; 95% CI, 0.62-1.25). However, AKI (32% vs. 12%; P = 0.0006; OR, 3.45; 95% CI, 1.67-7.13) was significantly more common in patients who received combination therapy. CONCLUSION: Novel ß-lactam-ß-lactamase inhibitors when used in combination with other antibiotics did not add clinical benefit compared to their use as monotherapy in the treatment of MDR P. aeruginosa infections. A Combination regimen was associated with an increased risk of nephrotoxicity.

Ceftolozane-Tazobactam Versus Ceftazidime-Avibactam for the Treatment of Infections Caused by Multidrug-Resistant Pseudomonas aeruginosa: a Multicenter Cohort Study.

Ceftolozane-tazobactam (C-T) and ceftazidime-avibactam (CAZ-AVI) are two novel antimicrobials that retain activity against resistant Pseudomonas aeruginosa. The comparative effectiveness and safety of C-T versus CAZ-AVI remain unknown. A retrospective, multicenter cohort study was performed in six tertiary centers in Saudi Arabia and included patients who received either C-T or CAZ-AVI for infections due to multidrug-resistant (MDR) P. aeruginosa. Overall in-hospital mortality, 30-day mortality, and clinical cure were the main study outcomes. Safety outcomes were also evaluated. A multivariate analysis using logistic regression was used to determine the independent impact of treatment on the main outcomes of interest. We enrolled 200 patients in the study (100 in each treatment arm). A total of 56% were in the intensive care unit, 48% were mechanically ventilated, and 37% were in septic shock. Approximately 19% of patients had bacteremia. Combination therapy was administered to 41% of the patients. The differences between the C-T and CAZ-AVI groups did not reach statistical significance in the overall in-hospital mortality (44% versus 37%; P = 0.314; OR, 1.34; 95% CI, 0.76 to 2.36), 30-day mortality (27% versus 23%; P = 0.514; OR, 1.24; 95% CI, 0.65 to 2.35), clinical cure (61% versus 66%; P = 0.463; OR, 0.81; 95% CI, 0.43 to 1.49), or acute kidney injury (23% versus 17%; P = 0.289; OR, 1.46; 95% CI, 0.69 to 3.14), even after adjusting for differences between the two groups. C-T and CAZ-AVI did not significantly differ in terms of safety and effectiveness, and they serve as potential options for the treatment of infections caused by MDR P. aeruginosa.

Ceftolozane-tazobactam vs. colistin for the treatment of infections due to multidrug-resistant Pseudomonas aeruginosa: a multicentre cohort study.

OBJECTIVES: The aim of this study was to compare the safety and effectiveness of ceftolozane-tazobactam (C-T) to colistin-based regimen for treating infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. METHODS: This was a retrospective, multicentre, observational cohort study of inpatients who received either C-T or intravenous colistin for treating infections caused by MDR P. aeruginosa. The study was conducted in five tertiary care hospitals in Saudi Arabia. The main study outcomes included clinical cure at end of treatment, in-hospital mortality, and acute kidney injury (AKI). Univariate analysis and multivariate logistic regression model were conducted to evaluate the independent effect of C-T on the clinical outcome. RESULTS: A total of 184 patients were included in the study: 82 patients received C-T, and 102 patients received colistin-based regimen. Clinical cure (77% vs. 57%; P = 0.005; OR, 2.52; 95% CI, 1.32-4.79) was significantly more common in patients who received C-T. After adjusting the difference between the two groups, treatment with C-T is independently associated with clinical cure (adjusted OR, 2.47; 95% CI, 1.16-5.27). In-hospital mortality (39% vs. 49%; P = 0.175; OR, 0.67; 95% CI, 0.37-1.20) was lower in patients who received C-T, but the difference was not significant. AKI (15% vs. 41%; P < 0.001; OR, 0.25; 95% CI, 0.12-0.51) was significantly less common in patients who received C-T. CONCLUSION: C-T is associated with a higher rate of clinical cure and lower rate of AKI compared to colistin. Our findings support the preferential use of C-T over colistin-based regimen for treating these infections.

Infectious diseases pharmacy practice, education, and research in Saudi Arabia: A review and future perspectives by the Infectious Diseases Pharmacy Specialty Network at the Saudi Society of Clinical Pharmacy.

Background: Infectious diseases (ID) pharmacy is one of the rapidly evolving clinical pharmacy specialties in the Kingdom of Saudi Arabia (KSA). There are gaps in the literature on ID pharmacy status in KSA. This review aimed to provide an update on the current status of several areas related to ID pharmacy in KSA, including practice, education, and research, and make pertinent recommendations for future development to achieve the KSA Vision, 2030, KSA Vision, 2030. Methods: This review was developed by a group of ID pharmacists working in different sectors under the umbrella of the ID Pharmacy Specialty Network (PSN) of the Saudi Society of Clinical Pharmacy (SSCP). The authors evaluated domains related to ID pharmacy in KSA and searched the literature for relevant articles. Based on the experts' assessment of the current gaps and challenges, recommendations were made for future improvement. Results: Several aspects of ID pharmacy in KSA were evaluated, including history and development, antimicrobial resistance (AMR), antimicrobial stewardship programs (ASP), roles of ID pharmacists, ID pharmacy education, and research. The biggest challenges include AMR, the varying levels of ASP implementation, and the low number of ID-trained pharmacists, especially in non-major cities. Several recommendations for improvement were discussed. Conclusion: Infectious diseases pharmacy has sustained remarkable progress in KSA in several areas. However, more efforts are needed to increase ASP implementation, increase the number of ID-trained pharmacists, and encourage ID pharmacists in publishing and participating in practice guidelines, which will eventually help achieve the KSA Vision, 2030, KSA Vision, 2030.

Severity of COVID-19 infection in ACEI/ARB users in specialty hospitals: A retrospective cohort study.

BACKGROUND: The uncertainty about COVID-19 outcomes in angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) users continues with contradictory findings. This study aimed to determine the effect of ACEI/ARB use in patients with severe COVID-19. METHODS: This retrospective cohort study was done in two Saudi public specialty hospitals designated as COVID-19 referral facilities. We included 354 patients with a confirmed diagnosis of COVID-19 between April and June 2020, of which 146 were ACEI/ARB users and 208 were non-ACEI/ARB users. Controlling for confounders, we conducted multivariate logistic regression and sensitivity analyses using propensity score matching (PSM) and Inverse propensity score weighting (IPSW) for high-risk patient subsets. RESULTS: Compared to non-ACEI/ARB users, ACEI/ARB users had an eight-fold higher risk of developing critical or severe COVID-19 (OR = 8.25, 95%CI = 3.32-20.53); a nearly 7-fold higher risk of intensive care unit (ICU) admission (OR = 6.76, 95%CI = 2.88-15.89) and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR = 4.77,95%CI = 2.15-10.55). Patients with diabetes, hypertension, and/or renal disease had a five-fold higher risk of severe COVID-19 disease (OR = 5.40,95%CI = 2.0-14.54]. These results were confirmed in the PSM and IPSW analyses. CONCLUSION: In general, but especially among patients with hypertension, diabetes, and/or renal disease, ACEI/ARB use is associated with a significantly higher risk of severe or critical COVID-19 disease, and ICU care.

Impact of antibiotic de-escalation on hospitalized patients with urinary tract infections: A retrospective cohort single center study.

BACKGROUND: Urinary tract infections (UTIs) can be caused by multiple drug-resistant bacteria. Empirical broad-spectrum antibiotics help minimize the risk of disease progression. Although antibiotic de-escalation is important to reduce resistance, adverse drug effects, and costs, few studies have evaluated the impact of antibiotic de-escalation on complicated UTIs in hospitalized patients. METHODS: In this retrospective cohort single center observational study conducted over a period of 1 year at Prince Sultan Military Medical City (PSMMC), the rate of antibiotic de-escalation following reporting culture and sensitivity results, hospital length of stay (LOS), and factors associated with antibiotic de-escalation failure were determined. RESULTS: Ninety-one patients were enrolled in this study. Baseline characteristics were comparable between groups. The rate of successful de-escalation was 29.7% (27 patients) while 70.3% (64 patients) failed to experience de-escalation. The median hospital LOS was significantly lower in successfully de-escalated patients, at 3 days interquartile range (IQR) (2-6), while in the failed group it was 10 days IQR (6-21) (p<0.001). However, the identified factor associated with failure was a multidrug-resistant (MDR) pathogen that was significantly higher in the failed group than in the successful group: 38 patients (59.4%) versus 6 patients (22.2%; p<0.001), respectively. CONCLUSION: Antibiotic de-escalation is an essential antimicrobial stewardship strategy. The findings of this study showed that de-escalation was associated with better patient outcomes (i.e., reduced hospital LOS) in patients admitted due to UTIs. In this study's site hospital, there is a potential for improving the current de-escalation rate. MDR pathogens were the only significant reason identified for de-escalation failure. Further data are needed on the large scale to evaluate reasons for de-escalation failure.

Vancomycin therapy in critically ill patients on continuous renal replacement therapy; are we doing enough?

BACKGROUND: Recommendations regarding vancomycin dosing and monitoring in critically ill patients on continuous renal replacement therapy (CRRT) are limited. This is a retrospective study to assess the adequacy of current vancomycin dosing and monitoring practice for patients on CRRT in a tertiary hospital in Riyadh, Saudi Arabia. METHODS: A retrospective chart review of adult patients admitted between 1 April 2011 and 30 March 2013 to critical care and received intravenous vancomycin therapy whilst on CRRT was performed. RESULTS: A total of 68 patients received intravenous vancomycin therapy whilst on CRRT, of which 32 met the inclusion criteria. Fifty-one percent were males and median (range) age was 62.5 (19 - 90) years. Median APACHE II score was 33.5 (22-43) and median Charlson Comorbidity Score was 4 (0-8). The mean (± standard deviation) dose of vancomycin was 879.9 mg (± 281.2 mg) for an average duration of 5.9 days (± 3.7 days). All patients received continuous veno-venous haemofiltration (CVVH). A total of 55 vancomycin level readings were available from the study population, ranging from 6.6 to 41.3, with wide variations within the same sampling time frames. Vancomycin levels of > 15 mg/L or were achieved at least once in 24 patients (75.0%), but only 11 patients (34.3%) had 2 or more serum vancomycin level readings of 15 mg/L or more. CONCLUSION: Therapeutic vancomycin levels are difficult to maintain in critically ill patients who are receiving IV vancomycin therapy whilst on CRRT. Aggressive dosing schedules and frequent monitoring are required to ensure adequate vancomycin therapy in this setting.

Physicians' knowledge, perceptions, and attitudes toward antimicrobial prescribing in Riyadh, Saudi Arabia.

OBJECTIVES: To assess knowledge, perceptions, and attitudes toward antimicrobial prescribing among physicians practicing in Riyadh, Saudi Arabia. METHODS: A questionnaire was developed and distributed to physicians working in hospitals in Riyadh, Saudi Arabia between June and August 2013. The results were analyzed using Stata 12 software. RESULTS: Two hundred and twelve (84.8%) full responses were returned. Most respondents perceived antimicrobial resistance as a significant problem in their daily practice (119, 56.1%) and at a national level (148, 69.8%). Inappropriate empirical therapy (101, 47.6%) and excessive use of antimicrobials in healthcare settings (66, 31.1%) were believed to be the main contributors to increasing bacterial resistance. Respondents favor treating infection rather than colonization (98, 46.2%), and physician education (74, 34.9%) as the most effective interventions to reduce antimicrobial resistance. Many respondents (95, 44.8%) do not feel confident in their knowledge of antimicrobial prescribing. Two-thirds of the respondents (135, 63.7%) have local antimicrobial guidelines, of which 90 (66.7%) felt were useful. Most respondents (160, 75.5%) considered their local infectious diseases service to be very helpful. CONCLUSION: There are considerable unmet training and education need for physicians in the area of antimicrobial prescribing. Local antimicrobial guidelines need revision to ensure they are more relevant and helpful for medical practitioners.

High dose intravenous colistin methanesulfonate therapy is associated with high rates of nephrotoxicity; a prospective cohort study from Saudi Arabia.

BACKGROUND: Nephrotoxicity is an important adverse effect of colistin methanesulfonate (CMS) therapy. No data exist on rates and risk factors for colistin-related nephrotoxicity in Saudi Arabia (SA). We conducted a prospective cohort study to identify rates and risk factors for CMS nephrotoxicity in our patient population. METHODS: We prospectively included adult patients who received ≥48 hours of intravenous CMS therapy. Pregnant patients and those on renal replacement were excluded. Patients received 9 million units (mU) loading dose followed by 3 mU 8 hourly. In renal impairment, CMS dosing was adjusted according to calculated creatinine clearance (CrCl). Nephrotoxicity was defined as per RIFLE criteria (Risk, Injury, Failure, Loss and End-stage renal disease). Statistical analysis was performed using SPSS version 20.0 (IBM, Armonk, New York, USA). The study was approved by the institution's Research Ethics Committee. RESULTS: A total of 67 patients were included in the study. Mean (±standard deviation) age was 57.5 (±24.0) years, Charlson Co-morbidity Score 2.88 (±2.39), CrCl 133.60 (±92.54) mL/min and serum albumin 28.65 (±4.45) g/L. Mean CMS dose was 0.11 (±0.04) mU/kg/day and mean total CMS dose received was 101.21 (±47.37) mU. Fifty-one (76.1%) patients developed RIFLE-defined nephrotoxicity. Mean total CMS dose and duration of therapy before onset of nephrotoxicity were 66.71 (±43.45) mU and 8.70 (±6.70) days, respectively. In bivariate analysis, patients with nephrotoxicity were significantly older (P 0.013) and had lower baseline serum albumin (P 0.008). Multivariate logistic regression identified serum albumin [odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57-0.93; P 0.010] and intensive care admission (OR 16.38; 95% CI 1.37-195.55; P 0.027) as independent risk factors for CMS nephrotoxicity. CONCLUSIONS: High dose intravenous CMS therapy is associated with high rates of nephrotoxicity in SA. Independent risk factors for colistin nephrotoxicity were baseline hypoalbuminemia and intensive care admission.

Update on colistin in clinical practice.

Considerable progress has been made in the last decade towards better understanding of the optimal clinical use of colistin. It has become evident that higher intravenous (iv) colistin methanesulfonate (CMS) doses are important, probably with the addition of a loading dose in critically ill patients. Higher CMS doses lead to increased risk of nephrotoxicity, which seems reversible in most cases. Intravenous colistin is reasonably efficacious, but should continue to be considered only in the absence of safer alternatives. Although theoretically appealing, there is insufficient evidence to support inhaled colistin mono-therapy in non-cystic fibrosis patients. Moreover, the balance of evidence available at present is not in favor of adjunctive inhaled colistin therapy. Intrathecal or intra-ventricular colistin administration are appropriate options for neurosurgical meningitis caused by colistin-susceptible, multidrug resistant gram-negative bacteria. Ongoing randomized, controlled trials will hopefully help decide if combining colistin with a carbapenem, fosfomycin, or rifampicin is of clinical advantage.