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.

Vancomycin vs metronidazole use for the treatment of Clostridioides difficile infection in a tertiary care hospital in Saudi Arabia.

Background: The 2017 Infectious Diseases Society of America (IDSA) Clostridioides difficile infection (CDI) guidelines recommendation for oral vancomycin as preferred treatment was based on studies conducted in North America, Australia, and Europe. According to recent published data, metronidazole remains a reasonable option. No studies have been conducted in Saudi Arabia to compare prescribing patterns before and after the release of the guidelines. Due to low CDI burden in Saudi Arabia, the aim is to assess the effectiveness and outcomes of vancomycin vs metronidazole treatment options. Methods: This was a retrospective cohort study conducted in a tertiary care hospital in Jeddah which was approved by the Institutional Review Board (IRB 2020-53). Data was collected from January 2017 to April 2020. Eligible patients were adults (>18 years old) diagnosed with CDI who either received oral metronidazole (500 mg 3 times daily) or oral vancomycin (125-500 mg 4 times daily). Patients who received a combination of treatment or who were diagnosed with fulminant CDI were excluded. Demographic data were collected. The primary outcome was to assess treatment response to initial therapy with oral metronidazole versus oral vancomycin. Secondary outcomes included assessing early treatment response, time to discharge after diagnosis, proportion of patients with a positive VRE surveillance culture within 6 months of diagnosis, 30-day recurrence and 30-day all-cause mortality. Chi-square or Fisher's exact test were used to examine differences in categorical variables while student t-test or Mann-Whitney test, were used to examine differences in continuous variables. P value < 0.05 was considered as significant. Results: A total of 166 patients were included in the analysis. Demographic characteristics were not significantly different between the two groups. There was no difference in treatment response between vancomycin and metronidazole (96.4 % versus 94.3 %, p = 0.682). However, compared with metronidazole, vancomycin treatment was significantly associated with better early response (94.0 % versus 77.8 %, p = 0.008). Other outcomes were not significantly different between the two drug groups for time to discharge after diagnosis (P = 0.522), 30-day recurrence (P > 0.99) and 30-day all-cause mortality (P = 0.782). Of note, the vancomycin versus metronidazole use before the 2017 IDSA guidelines (26 % versus 74 %) was completely reversed after the release of the guidelines (83.3 % versus 16.7 %), p < 0.001). Conclusion: The results of this study demonstrate that vancomycin and metronidazole have comparable outcomes in regards to treatment response for non-fulminant CDI. The study also reveals the high and quick impact of international guidelines on local prescription patterns. Further studies are needed in Saudi Arabia to guide the treatment of CDI.

The clinical impact of rifampicin-based anti-TB therapy and tenofovir alafenamide-containing ARV regimen drug Interaction in people living with HIV: Case series report.

BACKGROUND: People living with HIV (PLWH) are prone to developing tuberculosis (TB). Since tenofovir alafenamide (TAF) is the recommended tenofovir (TFV) prodrug and rifampicin is a key component of TB therapy, thus complicating HIV and TB coinfection management. However, there is little data regarding the impact of this drug-drug Interaction in PLWH, which makes health care providers reluctant to prescribe them together. METHODS: This was an observational, retrospective case series carried out at King Faisal Specialist Hospital & Research Center (KFSH&RC), Jeddah, Saudi Arabia. PLWH (≥18 years old) who received the TAF-containing ARV regimen and rifampicin-based anti-TB therapy together for ≥ 4 weeks were included. The objective of this study was to report the clinical impact of this drug-drug interaction (rifampicin + TAF-containing antiretroviral (ARV) regimen) on HIV viral load control in PLWH. RESULTS: A total of 7 PLWH who met the inclusion criteria, 5 (71 %) out of 7, were males. All patients received dolutegravir 50 mg twice daily (DTG) plus the combination of TAF 25 mg and emtricitabine 200 mg (FTC) once daily as their ARV regimen. Four patients had suppressed viral load levels at baseline, which was maintained throughout TB treatment. Three patients had unsuppressed viral load levels at baseline and attained viral load suppression throughout the TB treatment course CONCLUSION: Overall, the TAF-containing ARV regimen maintained it's efficacy in presence of rifampicin.

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.

Effect of Broad-Spectrum Antibiotic De-escalation on Critically Ill Patient Outcomes: A Retrospective Cohort Study.

PURPOSE: Antibiotic de-escalation (ADE) in critically ill patients is controversial. Previous studies mainly focused on mortality; however, data are lacking about superinfection. Therefore, we aimed to identify the impact of ADE versus continuation of therapy on superinfections rate and other outcomes in critically ill patients. METHODS: This was a two-center retrospective cohort study of adults initiated on broad-spectrum antibiotics in the intensive care unit (ICU) for ≥ 48 h. The primary outcome was the superinfection rate. Secondary outcomes included 30-day infection recurrence, ICU and hospital length of stay, and mortality. RESULTS: 250 patients were included, 125 in each group (ADE group and continuation group). Broad spectrum antibiotic discontinuation occurred at a mean of 7.2 ± 5.2 days in the ADE arm vs. 10.3 ± 7.7 in the continuation arm (P value = 0.001). Superinfection was numerically lower in the ADE group (6.4% vs. 10.4%; P = 0.254), but the difference was not significant. Additionally, the ADE group had shorter days to infection recurrence (P = 0.045) but a longer hospital stay (26 (14-46) vs. 21 (10-36) days; P = 0.016) and a longer ICU stay (14 (6-23) vs. 8 (4-16) days; P = 0.002). CONCLUSION: No significant differences were found in superinfection rates among ICU patients whose broad-spectrum antibiotics were de-escalated versus patients whose antibiotics were continued. Future research into the association between rapid diagnostics with antibiotic de-escalation in the setting of high resistance is warranted.

Efficacy and Safety of Bictegravir-Based Regimen in Pregnant Women Living with HIV: A Case Report.

Bictegravir (BIC) is included in international guidelines as the first line of therapy for patients living with Human Immunodeficiency Virus (HIV), either as initial therapy or as a replacement for patients with prior antiretroviral therapy (ART). Due to limited efficacy and safety data, BIC is currently not recommended during pregnancy. Data on the safety and efficacy of BIC during pregnancy were unavailable at the time of drug approval. In our case, BIC/TAF/FTC was effective in suppressing viral load (VL) in pregnancy, and there were no reported safety issues for the mother or the baby.

Tocilizumab effectiveness in mechanically ventilated COVID-19 patients (T-MVC-19 Study): a multicenter real-world evidence.

BACKGROUND: This study aimed to evaluate the effectiveness of tocilizumab in mechanically ventilated patients with coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: This retrospective multicenter study included adults (≥18 years) diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab, and requiring invasive mechanical ventilation during admission. Survival analyses with inverse propensity score treatment weighting (IPTW) and propensity score matching (PSM) were conducted. To account for immortal bias, we used Cox proportional modeling with time-dependent covariance. Competing risk analysis was performed for the extubation endpoint. RESULTS: A total of 556 (tocilizumab = 193, control = 363) patients were included. Males constituted the majority of the participants (69.2% in tocilizumab arm,74.1% in control arm). Tocilizumab was not associated with a reduction in mortality with hazard ratio [(HR) = 0.82,95% confidence interval (95%CI): 0.62-1.10] in the Inverse propensity score weighting (IPTW) analysis and (HR = 0.86,95% CI: 0.64-1.16) in the PSM analysis. However, tocilizumab was associated with an increased rate of extubation (33.6%) compared to the control arm (11.9%); subdistributional hazards (SHR) = 3.1, 95% CI: 1.86-5.16). CONCLUSIONS: Although tocilizumab was not found to be effective in reducing mortality, extubation rate while on mechanical ventilation was higher among tocilizumab treated group.

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.

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.