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.

Ceftazidime-Avibactam versus Colistin for the Treatment of Infections Due to Carbapenem-Resistant Enterobacterales: A Multicenter Cohort Study.

BACKGROUND: The aim of this study was to compare the safety and effectiveness of ceftazidime-avibactam (CAZ-AVI) to colistin-based regimen in the treatment of infections caused by carbapenem-resistant Enterobacterales (CRE). METHODS: This was a retrospective, multicenter, observational cohort study of inpatients who received either CAZ-AVI or intravenous colistin for treatment of infections due to CRE. The study was conducted in 5 tertiary care hospitals in Saudi Arabia. Main study outcomes included in-hospital mortality, clinical cure at end of treatment, and acute kidney injury (AKI). Univariate analysis and multivariate logistic regression model were conducted to assess the independent impact of CAZ-AVI on the clinical outcome. RESULTS: A total of 230 patients were included in this study: 149 patients received CAZ-AVI and 81 patients received colistin-based regimen. Clinical cure (71% vs 52%; P = 0.004; OR, 2.29; 95% CI, 1.31-4.01) was significantly more common in patients who received CAZ-AVI. After adjusting the difference between the two groups, treatment with CAZ-AVI is independently associated with clinical cure (adjusted OR, 2.75; 95% CI, 1.28-5.91). In-hospital mortality (35% vs 44%; P = 0.156; OR, 0.67; 95% CI, 0.39-1.16) was lower in patients who received CAZ-AVI but the difference was not significant. AKI (15% vs 33%; P = 0.002; OR, 0.37; 95% CI, 0.19-0.69) was significantly less common in patients who received CAZ-AVI. CONCLUSION: CAZ-AVI is associated with higher rate of clinical cure and lower rate of AKI compared to colistin. Our findings support the preferential use of CAZ-AVI over colistin-based regimen for treating these infections.

Resource Utilization and Caring Cost of People Living with Human Immunodeficiency Virus (PLHIV) in Saudi Arabia: A Tertiary Care University Hospital Experience.

The human immunodeficiency virus (HIV) is associated with a significant burden of disease, including medical and non-medical costs. Therefore, it is considered to be a priority for all health authorities. The aim of this study is to determine healthcare and treatment costs of caring for PLHIV at one of the tertiary care university hospitals in Riyadh, Saudi Arabia. This was a micro-costing, retrospective, observational study from a tertiary care university hospital and included all confirmed HIV-infected patients who visited infectious disease clinics in the period from 1 January 2015 to 31 December 2018. A total of 42 PLHIV were included in this study. The mean age of the study participants was 38.76 ± 11.47 years with a mean disease duration of 5.27 ± 4.81 years. The majority of patients were male (85.7%) and Saudi (88.1%). More than half of included patients (59.5%) had a CD4 count of more than 500. During the study period, 26 patients (61.9%) were initiated on a single-tablet regimen. Overall, the main cost-driver was antiretroviral medications, which cumulatively represented more than 64% of the total cost. Patients who developed opportunistic infections had a statistically significant (p = 0.033) higher financial impact, both as a total and on a patient level, than those presented without opportunistic infections. On a patient level, the mean and median costs were higher and statistically significant for those with co-morbidities than those without co-morbidities (p = 0.002). The majority of the economic burden of PLHIV is attributable to antiretroviral therapy use. The healthcare costs of PLHIV can vary greatly, depending on the presenting illness, clinical stage, developed opportunistic infection, co-morbidity, and pharmacological therapy.

Ceftazidime-avibactam for the Treatment of Multidrug-resistant Pseudomonas aeruginosa Central Nervous System Infection in Pediatric Patient: A Case Report.

Very limited experimental and clinical data are currently available regarding the cerebrospinal fluid (CSF) penetration of ceftazidime-avibactam in adults. Nevertheless, up to our knowledge, there are no data of ceftazidime-avibactam use in central nervous system infections in pediatric patients. For that, here we describe our experience with the use of ceftazidime-avibactam in addition to intraventricular colistin in a pediatric patient diagnosed with ventriculoperitoneal shunt infection due to multidrug-resistant P. aeruginosa. A 2-year-old boy known to pre-term, delivered at 26 weeks with hydrocephalus that required ventriculoperitoneal shunt which was infected due to P. aeruginosa. He was treated with multiple antipseudomonal agents; however, cultures remained persistently positive. On day 54 of admission, the isolate was reported as multidrug-resistant P. aeruginosa and he was switched to ceftazidime-avibactam and intraventricular colistin. CSF cultures became sterile 3 days after initiation of this antibiotic regimen, and subsequent CSF cultures had no growth. No recurrent episode of central nervous system infections due to P. aeruginosa occurred up to 2 years of follow-up.

Evaluating the Inappropriate Prescribing and Utilization of Caspofungin, a Four-Year Analysis at a Teaching Hospital in Saudi Arabia.

The appropriate use of antimicrobial agents improves clinical outcomes and reduces antimicrobial resistance. Nevertheless, data on inappropriate prescription and negative outcomes are inconsistent. The objective of this study was to assess the prescription appropriateness of Caspofungin at a tertiary teaching hospital in Saudi Arabia and the impact on mortality at 30 days. A retrospective chart review was performed for patients who received Caspofungin from May 2015 to December 2019 to obtain prescription information and culture and susceptibility tests. The appropriateness of the dosage (ApD), initiation time (ApI), agent selection (ApS), and duration of therapy (ApDUR) was evaluated based on recommendations of the infectious diseases society of America. 355 eligible patients who received 3458 Caspofungin doses were identified. Their median age was 54 years (range 18-96). Overall, 270 (76.1%) patients received empirical prescriptions, of which 74.4% had the appropriate dose, and 56.3% had received it for more than five days, despite no proven Candida infection. This was not influenced by past medical history (p = 0.394). Only 39% of patients who received definitive prescriptions met all four study criteria for appropriate prescription. Therefore, antimicrobial stewardship programs can improve the appropriate utilization of antifungal therapies.

Aerosolized plus intravenous colistin vs intravenous colistin alone for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria: A retrospective cohort study.

OBJECTIVE: To compare the effectiveness and safety of aerosolized (AER) plus intravenous (IV) colistin with IV colistin alone in patients with nosocomial pneumonia (NP) due to multidrug-resistant (MDR) Gram-negative bacteria. METHODS: This was a retrospective cohort study of adults with NP who received IV colistin alone or in combination with AER colistin. The primary endpoint was clinical cure at end of therapy. Secondary endpoints included microbiological eradication, in-hospital mortality and nephrotoxicity. RESULTS: In total, 135 patients were included in this study: 65 patients received AER plus IV colistin and 70 patients received IV colistin alone. Baseline characteristics were similar between the two groups. Clinical cure was achieved in 42 (65%) patients who received AER plus IV colistin and 26 (37%) patients who received IV colistin alone (P = 0.01). Among a total of 88 patients who were microbiologically evaluable, 27 (42%) patients who received AER plus IV colistin and 12 (17%) patients who received IV colistin alone attained favourable microbiological outcomes (P = 0.022). In-hospital mortality (43% vs 59%, P = 0.072) was higher in patients who received IV colistin alone, but the difference was not significant. Renal injury occurred in 31% of patients who received AER plus IV colistin and in 41% of patients who received IV colistin alone (P = 0.198). CONCLUSION: AER colistin can be considered as salvage therapy as an adjunct to IV administration for the treatment of patients with NP due to MDR Gram-negative pathogens.

Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Blockers With Severity of COVID-19: A Multicenter, Prospective Study.

BACKGROUND: Speculations whether treatment with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) predisposes to severe coronavirus disease 2019 (COVID-19) or worsens its outcomes. This study assessed the association of ACE-I/ARB therapy with the development of severe COVID-19. METHODS: This multi-center, prospective study enrolled patients hospitalized for COVID-19 and receiving one or more antihypertensive agents to manage either hypertension or cardiovascular disease. ACE-I/ARB therapy associations with severe COVID-19 on the day of hospitalization, intensive care unit (ICU) admission, mechanical ventilation and in-hospital death on follow-up were tested using a multivariate logistic regression model adjusted for age, obesity, and chronic illnesses. The composite outcome of mechanical ventilation and death was examined using the adjusted Cox multivariate regression model. RESULTS: Of 338 enrolled patients, 245 (72.4%) were using ACE-I/ARB on the day of hospital admission, and 197 continued ACE-I/ARB therapy during hospitalization. Ninety-eight (29%) patients had a severe COVID-19, which was not significantly associated with the use of ACE-I/ARB (OR 1.17, 95% CI 0.66-2.09; P = .57). Prehospitalization ACE-I/ARB therapy was not associated with ICU admission, mechanical ventilation, or in-hospital death. Continuing ACE-I/ARB therapy during hospitalization was associated with decreased mortality (OR 0.22, 95% CI 0.073-0.67; P = .008). ACE-I/ARB use was not associated with developing the composite outcome of mechanical ventilation and in-hospital death (HR 0.95, 95% CI 0.51-1.78; P = .87) versus not using ACE-I/ARB. CONCLUSION: Patients with hypertension or cardiovascular diseases receiving ACE-I/ARB therapy are not at increased risk for severe COVID-19 on admission to the hospital. ICU admission, mechanical ventilation, and mortality are not associated with ACE-I/ARB therapy. Maintaining ACE-I/ARB therapy during hospitalization for COVID-19 lowers the likelihood of death. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT4357535.

Clinical Characteristics and Outcome of Hospitalized COVID-19 Patients in a MERS-CoV Endemic Area.

BACKGROUND: The Kingdom of Saudi Arabia (KSA) reported 170,639 cases and 1430 deaths from COVID-19 since the first case emerged in the country on March 2 through June 25, 2020. The objective of this report is to describe the characteristics and outcome observed among 99 hospitalized COVID-19 patients in the largest academic hospital in KSA, and assess co-infection with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). METHODS: This single-center case series data included select epidemiological, clinical, radiological features and laboratory findings of all confirmed hospitalized cases of COVID-19 in King Saud University Medical City (KSUMC), Riyadh, KSA, from March 22 until May 31, 2020, followed through June 6, 2020. We conducted retrospective analysis of listed data from 99 hospitalized patients and present characteristics and factors associated with severity in percentages and univariate odds ratios. Cases were confirmed using nasopharyngeal or throat swab by real-time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and MERS-CoV by RT-PCR. RESULTS: The 99 hospitalized COVID-19 patients included in this analysis constitute 16% of 632 positive SARS-CoV-2 among 6633 persons who were tested at the KSUMC (positivity rate, 9.4%). MERS-CoV PCR was negative in all 99 patients tested. The majority of these 99 hospitalized patients were males (66%), had a mean age of 44 years (range, 19-87), and a quarter (25.3%) were health care workers. Patients with comorbid conditions accounted for 52.5% of patients including the 8.1% who were asymptomatic; diabetes mellitus being the most frequent (31.3%), followed by hypertension (22.2%). The most common presenting symptoms were fever (67.7%), cough (60.6%), dyspnea (43.4%), upper respiratory symptoms (27.3%), fatigue (26.3%), diarrhea (19.2%) and loss of smell (9.1%). The clinical conditions among these 99 patients included upper respiratory tract infection (47.5%), abnormal chest X-ray, lymphopenia, high inflammatory markers a fifth (21%) of patients had moderate pneumonia, while 7% had severe pneumonia with 22.2% requiring admission to the intensive care unit and 12.1% died. Late presentation with severe disease, an abnormal chest X-ray, lymphopenia, high inflammatory markers (C-reactive protein, ferritin, and procalcitonin), and end organ damage (high creatinine or high aspartate aminotransferase) were predictors for admission to critical care unit or died. CONCLUSION: We observed no MERS-CoV co-infection in this early cohort of hospitalized COVID-19 patients who were relatively young, more than half had comorbid conditions, presented with fever and/or cough, an abnormal chest X-ray, lymphopenia, and high inflammatory markers. Given MERS-CoV endemicity in the country, co-monitoring of MERS-CoV and SARS-CoV-2 coinfection is critical.

Inhaled colistin for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria: A real-life experience in tertiary care hospitals in Saudi Arabia.

BACKGROUND: Nosocomial pneumonia (NP) due to multidrug-resistant (MDR) Gram-negative pathogens, has continued to rise over the last several decades. Parenteral administration of colistin results in poor alveolar penetration and subtherapeutic concentration; therefore, direct drug deposition at site of infection may improve the effectiveness while minimizing the systemic exposure. The aim of this study is to describe the safety and effectiveness of inhaled colistin for the treatment of NP caused by MDR Gram-negative pathogens. METHOD: Patients who received inhaled colistin from May 2015 to May 2019 at 2 different tertiary care hospitals in Riyadh, Saudi Arabia were identified from pharmacy databases and their charts were retrospectively reviewed. RESULTS: 86 patients were enrolled in this study. The mean age was 56 ± 20 years. The mean Acute Physiology and Chronic Health Evaluation (APACHE II) was 17 ± 5. The responsible pathogens for NP were Pseudomonas aeruginosa (60%) Acinetobacter baumannii (28%), and Klebsiella pneumoniae (9%). Most patients (76/86) received concomitant intravenous antibiotics. Mean colistin total daily dose was 6 ± 3 million international units divided into 2-3 doses. Mean inhaled colistin duration of therapy was 11 ± 6 days. Favorable clinical outcome was achieved in 51 (59%) patients while favorable microbiological outcome occurred in 29 (34%) patients. Death due to all causes was noted in 39 (45%) cases. Renal injury occurred in 19 (22%) patients, all received concomitant intravenous colistin. CONCLUSION: Inhaled colistin can be considered as salvage therapy as adjunct to intravenous administration for treatment of patients with NP due to MDR Gram-negative pathogens.