Switch to oral antibiotics in Gram-negative bacteraemia: a randomized, open-label, clinical trial.

OBJECTIVES: To evaluate the safety and efficacy of switching from intravenous (IV) to oral antimicrobial therapy in patients with Enterobacterales bacteraemia, after completion of 3-5 days of microbiologically active IV therapy. METHODS: A multicentre, open-label, randomized trial of adults with monomicrobial Enterobacterales bacteraemia caused by a strain susceptible to ≥1 oral beta-lactam, quinolone, or trimethoprim/sulfamethoxazole. Inclusion criteria included completion of 3-5 days of microbiologically active IV therapy, being afebrile and haemodynamically stable for ≥48 hours, and absence of an uncontrolled source of infection. Pregnancy, endocarditis, and neurological infections were exclusion criteria. Randomization, stratified by urinary source of bacteraemia, was to continue IV (IV Group) or to switch to oral therapy (Oral Group). Agents and duration of therapy were determined by the treating physicians. The primary endpoint was treatment failure, defined as death, need for additional antimicrobial therapy, microbiological relapse, or infection-related re-admission within 90 days. Non-inferiority threshold was set at 10% in the 95% CI for the difference in the proportion with treatment failure between the Oral and IV Groups in the modified intention-to-treat population. The protocol was registered at ClinicalTrials.gov (NCT04146922). RESULTS: In the modified intention-to-treat population, treatment failure occurred in 21 of 82 (25.6%) in the IV Group, and 18 of 83 (21.7%) in the Oral Group (risk difference -3.7%, 95% CI -16.6% to 9.2%). The proportions of subjects with any adverse events (AE), serious AE, or AE leading to treatment discontinuation were comparable. DISCUSSION: In patients with Enterobacterales bacteraemia, oral switch, after initial IV antimicrobial therapy, clinical stability, and source control, is non-inferior to continuing IV therapy.

Elizabethkingia meningoseptica Infection in COVID-19 Patients.

Bacterial and fungal coinfections including the emergence of antimicrobial resistance are well-recognized in the era of coronavirus disease 2019 (COVID-19) infections. We present three cases of Elizabethkingia meningoseptica (EM), superinfections in COVID-19 patients admitted between the period of April 2021 and May 2021. All cases were intubated; had central venous catheters, had received prior antibiotics and antivirals as well as dexamethasone as part of severe COVID-19 management. Only one patient received anakinra. EM isolates were resistant to most available antibiotics and patients infected with it had poor treatment outcomes.

Chorioamnionitis and neonatal sepsis due to extended-spectrum beta-lactamase-producing Escherichia coli infection: a case report.

Chorioamnionitis is an acute inflammation of the membranes and chorion of the placenta typically due to ascending polymicrobial infection in the setting of membrane rupture. It is a common complication of pregnancy associated with significant maternal, perinatal, and long-term adverse outcomes. We present a case of placental infection leading to preterm delivery, severe neonatal sepsis, maternal wound infection, postnatal readmission, and prolonged hospital stay. This virulent infection was caused by multidrug-resistant extended-spectrum beta-lactamase (ESBL)-producing Escherichia Coli (E. Coli), which represent a major worldwide threat according to the Centre for Disease Control and Prevention (CDC). It was managed with appropriate antibiotic therapy, patient-centered approach, and multidisciplinary team involvement that led to favourable maternal and neonatal outcome.

Mortality incidence among critically ill burn patients infected with multidrug-resistant organisms: A retrospective cohort study.

INTRODUCTION: Many risk factors have been reported to increase mortality among burn patients. Previously, a higher mortality incidence was reported in acute burn patients infected with multidrug-resistant organisms (MDROs) when compared to patients infected with non-MDROs. However, considering this as an independent risk factor for mortality in acute burn patients is not yet confirmed. METHODS: We conducted an observational retrospective study in Qatar. We included adult patients admitted to the surgical intensive care unit (ICU) between January 2015 and December 2017 with burn injuries involving either at least 15% of the total body surface area (TBSA) or less than 15% with facial involvement. All patients developed infection with a positive culture of either MDRO or non-MDRO. The primary outcome was in-hospital mortality. Other outcomes included days of mechanical ventilation, ICU, length of stay in hospital, and requirement of vasoactive agents. RESULTS: Fifty-eight patients were included in the final analysis: 33 patients in the MDRO group and 25 patients in the non-MDRO group. Six patients (18.2%) died in the MDRO group versus four patients (16%) in the non-MDRO group (P = 1). No significant difference was observed between the two groups with regard to the ICU length of stay. However, there was a trend towards increased median length of stay in hospital in the MDRO group: 62 days versus 45 days in the non-MDRO group (P = 0.057). No significant differences were observed in the other outcomes. CONCLUSION: In severely burned patients, infection with MDRO was not associated with increased mortality. There was a trend towards increased hospitalisation in MDRO-infected patients. Further studies with a larger sample size are needed to confirm these results. LAY SUMMARY: Many factors affect mortality in burn patients admitted to the intensive care unit, such as age, total body surface area involved in the injury, and others. In this retrospective study, we evaluated whether wound infection with a bacterial organism resistant to multiple classes of antibiotics (multidrug-resistant) is considered an independent risk factor for mortality in critically ill burn patients. We included 58 patients requiring intensive care admission with burn injuries involving 15% or more of the total body surface area or less than 15% but with facial involvement. A total of 33 patients were infected with multidrug-resistant organisms (MDROs) and 25 patients with non-MDROs. Six patients (18.2%) from the MDRO group died versus four (16%) in the non-MDRO group. The MDRO group required a longer stay in hospital and an average of one more day on a mechanical ventilator. We concluded that wound infection with MDROs might not increase mortality when compared to wound infection with non-MDROs, although other studies with a larger number of patients involved need to be conducted to validate these results.

Experience of treating Candida auris cases at a general hospital in the state of Qatar.

BACKGROUND AND OBJECTIVES: So far there have been no studies on Candida auris in Qatar. This study aimed to describe the clinical spectrum and outcome of C. auris infection in patients admitted to a general hospital in Qatar. METHODS: We conducted this descriptive observational study in a general hospital in Qatar. We have involved all patients with C. auris infection and colonization admitted to a general hospital from December 2018 to August 2019. RESULTS: We identified 13 patients with confirmed C.auris infection/colonization, of which five cases represented an actual C. auris infection, while the remaining eight cases were considered as colonization. The mean age of the patients with infection was 76.6 ± 8.4 years, while the mean age of the patients with colonization was 66.4 ± 24.7 years. Among the individuals clinically infected with C. auris, two had urinary tract infections, one had candidemia, one acquired soft tissue infection, and one had a lower respiratory tract infection. All strains of C. auris were susceptible to echinocandins, flucytosine, and posaconazole while resistance to fluconazole and amphotericin B. Of the patients with C. auris infection who received systemic antifungal therapy, three (60%) died during antifungal therapy. CONCLUSION: Our study showed that C. auris can cause a wide variety of invasive infections, including bloodstream infection, urinary tract infection, skin infection, and lower respiratory tract infections, especially in critically ill patients. In addition, our isolates showed resistance to the most common antifungal agents such as fluconazole and amphotericin B.

Tuberculosis of pancreas, the first case reported from Qatar.

Despite the high prevalence of tuberculosis (TB) in developing countries, primary pancreatic TB is a rare entity. We present a case of pancreatic TB in an immunocompetent patient who was found to have pancreatic mass resembling malignancy. A 40-year-old Indian male presented to the medical emergency room with complaints of abdominal pain and fever for 2 weeks' duration. He had a history of unintentional weight loss of about 20 pounds in the past 2 months. There was no significant history of exposure to TB patient. Family history was unremarkable for any malignancy. On examination, the significant finding was epigastric tenderness. He was thoroughly investigated, his purified protein derivative and QuantiFERON were negative. Chest X-ray was unremarkable. Computed tomography scan abdomen was performed that revealed large heterogenous necrotic mass in the lesser sac likely arising from pancreatic body with possible infiltration of the stomach, left lobe of the liver and encasing celiac vessels and portal vein with multiple peripancreatic and retroperitoneal necrotic lymph nodes. Endoscopic ultrasound with fine-needle aspiration of pancreatic mass was done, biopsy specimen revealed the presence of inflammation with no evidence of malignancy. TB polymerase chain reaction and culture came positive for Mycobacterium tuberculosis. He was started on antituberculosis treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol with a plan to continue for total 6 months. However, follow-up of the patient could not be done as he traveled back to his home country.

Clinical and Pharmacokinetic Outcomes of Peak-Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial.

BACKGROUND: Vancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration-time curve to minimum inhibitory concentration cure breakpoints (AUC24/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date. OBJECTIVES: We aimed to compare clinical and pharmacokinetic outcomes between peak-trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC24/MIC and cure rates. METHODS: A multicentered pragmatic parallel-group RCT was conducted in Hamad Medical Corporation hospitals in Qatar. Adult non-dialysis patients initiated on vancomycin were randomized to peak-trough-based or trough-only-based vancomycin TDM. Primary endpoints included vancomycin AUC24/MIC ratio breakpoint for cure and clinical effectiveness (therapeutic cure vs therapeutic failure). Descriptive, inferential, and classification and regression tree (CART) statistical analyses were applied. NONMEM.v.7.3 was used to conduct population pharmacokinetic analyses and AUC24 calculations. RESULTS: Sixty-five patients were enrolled [trough-only-based-TDM (n = 35) and peak-trough-based-TDM (n = 30)]. Peak-trough-based TDM was significantly associated with higher therapeutic cure rates compared to trough-only-based TDM [76.7% vs 48.6%; p value = 0.02]. No statistically significant differences were observed for all-cause mortality, neutropenia, or nephrotoxicity between the two groups. Compared to trough-only-based TDM, peak-trough-based TDM was associated with less vancomycin total daily doses by 12.05 mg/kg/day (p value = 0.027). CART identified creatinine clearance (CLCR), AUC24/MIC, and TDM approach as significant determinants of therapeutic outcomes. All patients [n = 19,100%] with CLCR ≤ 7.85 L/h, AUC24/MIC ≤ 1256, who received peak-trough-based TDM achieved therapeutic cure. AUC24/MIC > 565 was identified to be correlated with cure in trough-only-based TDM recipients [n = 11,84.6%]. No minimum AUC24/MIC breakpoint was detected by CART in the peak-trough-based group. CONCLUSION: Maintenance of target vancomycin exposures and implementation of peak-trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings.

Pneumococcal Meningitis Complicated by Cerebral Vasculitis, Abscess, Hydrocephalus, and Hearing Loss.

Intracranial abscesses, postinfectious vasculitis, and hydrocephalus are rare complications of Streptococcus pneumoniae (S. pneumoniae) meningitis, and to our knowledge, there have been no case reports where all these 3 complications occurred in a single patient with Streptococcus pneumoniae meningitis. Here, we report a case of a 48-year-old male who developed postinfectious vasculitis, abscess, hydrocephalus, and hearing loss after S. pneumoniae meningitis. Clinicians ought to be aware of the possible adverse outcomes of S. pneumoniae meningitis and the limitations of current treatment options.