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.

Clinical manifestations and outcome of Mpox infection in Qatar: An observational study during the 2022 outbreak.

Mpox emerged in May 2022 as a global outbreak, mostly in hitherto non-endemic countries. To describe the epidemiological and clinical characteristics of mpox in Qatar, data were retrospectively retrieved for all laboratory-confirmed mpox cases diagnosed in Qatar between May and November 2022. Twelve cases were identified; of which 10 were males, and the median age was 33.5 years (IQR 24.5-37.5). Recent sexual exposure was reported in 9 patients, 6 of which were outside Qatar. Seven individuals reported exclusive heterosexual contact. Pleomorphic skin lesions were present in all cases, with anogenital involvement in 11. Fever (7/12) and lymphadenopathy (4/12) were relatively common. All cases were HIV-negative. The majority of cases had an uncomplicated and self-limiting clinical illness. In conclusion, the majority of early mpox infections in Qatar were purportedly acquired through heterosexual contact, primarily among middle-aged men. The clinical course was mostly uneventful. In the absence of active case finding and the mild and self-limiting nature of the clinical illness, undetected community transmission cannot be ruled out.

Central catheter-related Gordonia bronchialis bacteremia in an immunocompromised patient: A case report, and literature review.

Gordonia is a rarely reported organism causing central line-associated bloodstream infection (CLABSI). This article reports an acute myeloid leukemia (AML) case in which the patient developed febrile neutropenia and was later found to have Gordonia bronchialis (G. bronchialis) CLABSI. The patient received a two-week ceftriaxone regimen, based on susceptibility. The microbiologic diagnosis of this organism is considered challenging due to its resemblance with other organisms; however, more sophisticated methods of diagnosis (such as gene sequencing) can aid in differentiation.

Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study.

Introduction: The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine. Methods: Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine. Results and discussion: Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants' CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.

Effectiveness of the neutralizing antibody sotrovimab among high-risk patients with mild-to-moderate SARS-CoV-2 in Qatar.

OBJECTIVES: To estimate the real-world effectiveness of sotrovimab against severe, critical, or fatal COVID-19 in Qatar at a time in which most SARS-CoV-2 incidences occurred due to the BA.2 Omicron subvariant. METHODS: We conducted a matched case-control study among all individuals eligible for sotrovimab treatment per United States Food and Drug Administration guidelines in the resident population of Qatar. The odds of progression to severe forms of COVID-19 were compared in cases (treatment group) versus controls (eligible patients who opted not to receive the treatment). Subgroup analyses were conducted. RESULTS: A total of 3364 individuals were eligible for sotrovimab treatment during the study period, of whom 519 individuals received the treatment, whereas the remaining 2845 constituted the controls. The adjusted odds ratio of disease progression to severe, critical, or fatal COVID-19 comparing the treatment group to the control group was 2.67 (95% confidence interval 0.60-11.91). In the analysis including only the subgroup of patients at higher risk of severe forms of COVID-19, the adjusted odds ratio was 0.65 (95% confidence interval 0.17-2.48). CONCLUSION: There was no evidence for a protective effect of sotrovimab in reducing COVID-19 severity in a setting dominated by the BA.2 subvariant.

COVID-19 disease severity in persons infected with the Omicron variant compared with the Delta variant in Qatar.

Background: Understanding the disease severity associated with the Omicron variant of the SARS-CoV-2 virus is important in determining appropriate management strategies at the individual and population levels. We determined the severity of SARS-CoV-2 infection in persons infected with the Omicron vs the Delta variant. Methods: We identified individuals with SARS-CoV-2 infection with Delta and propensity-score matched controls with Omicron variant infection from the National COVID-19 Database in Qatar. We excluded temporary visitors to Qatar, those with a prior documented infection, those ≤18 years old, and those with <14 days of follow up after the index test positive date. We determined the rates of admission to the hospital, admission to intensive care unit, mechanical ventilation, or death among those infected with the Delta or Omicron variants. Results: Among 9763 cases infected with the Delta variant and 11 310 cases infected with the Omicron variant, we identified 3926 propensity-score matched pairs. Among 3926 Delta infected, 3259 (83.0%) had mild, 633 (16.1%) had moderate and 34 (0.9%) had severe/critical disease. Among 3926 Omicron infected, 3866 (98.5%) had mild, 59 (1.5%) had moderate, and only 1 had severe/critical disease (overall P < 0.001). Factors associated with less moderate or severe/critical disease included infection with Omicron variant (aOR = 0.06; confidence interval (CI) = 0.05-0.09) and vaccination including a booster (aOR = 0.30; 95% CI = 0.09-0.99). Conclusions: Omicron variant infection is associated with significantly lower severity of disease compared with the Delta variant. Vaccination continues to offer strong protection against severe/critical disease.

Intrauterine infection and postpartum bacteremia due to Streptococcus gallolyticus subsp gallolyticus: An emerging concern.

Streptococcus gallolyticus is a gram-positive coccus belonging to the family Streptococcus bovis/Streptococcus equinus complex (SBSEC). Most cases of SBSEC bacteremia are reported in elderly males with underlying hepatobiliary disease and associated with infective endocarditis (IE) or colonic malignancy. The gastrointestinal tract is the most common portal of entry, followed by the urinary tract and hepatobiliary tree. We present 5 cases of intrapartum bacteremia caused by S. gallolyticus subsp gallolyticus reported from the labor unit of our hospital from 2019 to 2021. There was histopathological or microbiological evidence of chorioamnionitis in each case. All the mothers were below the age of 35 years, and none of them had underlying hepatobiliary or colonic disease. All maternal antenatal screenings for group B streptococci (GBS) were negative. All the isolates were susceptible to penicillins, ceftriaxone, carbapenems, and vancomycin. Three of them were treated with ceftriaxone and two with aminopenicillins. Duration of treatment varied from 8 days to 14 days. None of the babies were low birth weight or pre-term. All but one baby had clinical sepsis requiring neonatal intensive care unit (NICU) stay, with one having evidence of meningitis and three respiratory distress syndromes (RDS). None of the babies had S. gallolyticus bacteremia. All mothers and babies made a complete recovery without any complications. These cases suggest that S. gallolyticus subsp gallolyticus can be a rare but emerging cause of intrauterine infection complicated by post-partum bacteremia. There is possibility of colonization of maternal genital tract with S. gallolyticus causing neonatal infection.

Coronavirus Disease 2019 Disease Severity in Children Infected With the Omicron Variant.

SHORT SUMMARY: Severe acute respiratory syndrome coronavirus 2 infection from the Omicron variant in children/adolescents is less severe than infection from the Delta variant. Those 6 to <18 years also have less severe disease than those <6 years old. BACKGROUND: There are limited data assessing coronavirus 2019 (COVID-19) disease severity in children/adolescents infected with the Omicron variant. METHODS: We identified children and adolescents <18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with Delta and propensity score-matched controls with Omicron variant infection from the National COVID-19 Database in Qatar. Primary outcome was disease severity, determined by hospital admission, admission to the intensive care unit (ICU), or mechanical ventilation within 14 days of diagnosis, or death within 28 days. RESULTS: Among 1735 cases with Delta variant infection between 1 June and 6 November 2021, and 32 635 cases with Omicron variant infection between 1 January and 15 January 2022, who did not have prior infection and were not vaccinated, we identified 985 propensity score-matched pairs. Among those who were Delta infected, 84.2% had mild, 15.7% had moderate, and 0.1% had severe/critical disease. Among those who were Omicron infected, 97.8% had mild, 2.2% had moderate, and none had severe/critical disease (P < .001). Omicron variant infection (vs Delta) was associated with significantly lower odds of moderate or severe/critical disease (adjusted odds ratio [AOR], 0.12; 95% confidence interval [CI], .07-.18). Those aged 6-11 and 12 to <18 years had lower odds of developing moderate or severe/critical disease compared with those younger than age 6 years (aOR, 0.47; 95% CI, .33-.66 for 6-11 year olds; aOR, 0.45; 95% CI, .21-.94 for 12 to <18 year olds). CONCLUSIONS: Omicron variant infection in children/adolescents is associated with less severe disease than Delta variant infection as measured by hospitalization rates and need for ICU care or mechanical ventilation. Those 6 to <18 years of age also have less severe disease than those <6 years old.

The initial impact of a national BNT162b2 mRNA COVID-19 vaccine rollout.

OBJECTIVE: This study examined the initial impact of a national BNT162b2 vaccine rollout on SARS-CoV-2 infections in Qatar. METHODS: All individuals who had completed ≥14 days of follow-up by 16 March 2021 after receiving the BNT162b2 vaccine were included. This study calculated incidence rates (IR) and their 95% confidence intervals (CI) during days 1-7, 8-14, 15-21, 22-28, and >28 days post-vaccination. Poisson regression was used to calculate incidence rate ratios (IRR) relative to the first 7-day post-vaccination period. RESULTS: A total of 199,219 individuals with 6,521,124 person-days of follow-up were included. SARS-CoV-2 infection was confirmed in 1877 (0.9%), of which 489 (26.1%) were asymptomatic and 123 (6.6%) required oxygen support. The median time from first vaccination to SARS-CoV-2 confirmation was 11.9 days (IQR 7.7-18.2). Compared with the first 7-day post-vaccination period, SARS-CoV-2 infections were lower by 65.8-84.7% during 15-21, 22-28, and >28 days (P < 0.001 for each). For severe COVID-19, the incidence rates were 75.7-93.3% lower during the corresponding time periods (P < 0.001 for each). CONCLUSION: The results were consistent with an early protective effect of BNT162b2 vaccine against all degrees of SARS-CoV-2 severity.

Convalescent plasma for the treatment of patients with severe coronavirus disease 2019: A preliminary report.

BACKGROUND: The role of convalescent plasma therapy for patients with coronavirus disease 2019 (COVID-19) is unclear. METHODS: We retrospectively compared outcomes in a cohort of critical COVID-19 patients who received standard care (SC Group) and those who, in addition, received convalescent plasma (CP Group). RESULTS: In total, 40 patients were included in each group. The median patient age was 53.5 years (interquartile range [IQR] 42-60.5), and the majority of patients required invasive ventilation (69, 86.2%). Plasma was harvested from donors after a median of 37 days (IQR 31-46) from the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) result and 26 days (IQR 21-32) after documented viral clearance; it was administered after a median of 10 days (IQR 9-10) from the onset of symptoms and 2.5 days (IQR 2-4) from admission to intensive care unit. The primary endpoint of improvement in respiratory support status within 28 days was achieved in 26 patients (65%) in the SC Group and 31 patients (77.5%) in the CP Group (p = .32). The 28-day all-cause mortality (12.5% vs. 2.5%; p = .22) and viral clearance (65% vs. 55%; p = .49) were not significantly different between the two groups. Convalescent plasma was not significantly associated with the primary endpoint (adjusted hazard ratio 0.87; 95% confidence interval 0.51-1.49; p = .62). Adverse events were balanced between the two study groups. CONCLUSION: In severe COVID-19, convalescent plasma therapy was not associated with clinical benefits. Randomized trials are required to confirm our findings.

Clinical characteristics, microbiology, and outcomes of infective endocarditis in Qatar.

BACKGROUND: Infective endocarditis (IE) is a serious and potentially life-threatening disease. The epidemiology, treatment options, and outcomes have changed considerably over the last two decades. The aim of the study was to describe the epidemiology, clinical characteristics, and outcomes of patients with IE in Qatar. METHODS: Patients were identified from Hamad Medical Corporation hospitals' electronic records, the national referral center for the State of Qatar. We included those aged ≥ 18 years with Duke Criteria-based diagnosis of IE during the period from January 2015 to September 2017. Demographic and clinical data were retrieved. Descriptive statistics were performed, and logistic regression analysis was used to describe the relationship between patient characteristics and all-cause in-hospital mortality. All potentially relevant variables were included in the univariate analysis, while those with p < 0.1 in the univariate logistic regression model were included in the multivariate analysis. For the final model, we calculated odds ratios (OR) adjusted for each of the variables included, along with their 95% confidence intervals (95% CI). Data were analyzed using STATA software version 15 (StataCorp, College Station, Texas, USA). The study was approved by the Institutional Research Board with a waiver for informed consent. RESULTS: Fifty-seven cases were included, of which 70% were males. The mean age was 51 years ( ± 16.8 years). Eleven (19%) were associated with prosthetic valves, and 6 (11%) with implantable cardiac devices. Fever (84%), dyspnea (46%), and heart failure (37%) were the most common presentations. Only 58% of patients had known preexisting valvular heart disease or an intracardiac device. Skin infections (10 patients, 18%) were the most prevalent portals of infection, followed by venous catheters, recent valve surgery, and implantable cardiac devices. Staphylococci were implicated in 19 (34%) and Streptococcaceae in 9 (16%) patients, whereas 21 (37%) patients were culture negative. Left-side IE (49 patients, 86%) was predominant. Acute kidney injury (AKI) (17 patients, 30%) and heart failure (11 patients, 19%) were common complications. The majority of patients received targeted antimicrobial therapy with at least two active agents. Only 9 (16%) patients underwent surgical intervention. Fourteen (25%) patients died of any cause before hospital discharge. Logistic regression analysis identified septic shock [OR 57.8, 95% CI 2.6-1360.2; p < 0.01] and AKI OR 33.9, 95% CI 2.9-398.1; p < 0.01) as the only risk factors independently associated with in-hospital mortality. CONCLUSION: Staphylococci are the most common microbiological cause of IE in Qatar. Surgical intervention is uncommon, and mortality is relatively high. Our findings suggest that efforts should be directed toward improving IE prevention strategies in high-risk patients, encouraging early microbiological investigations and improving medical and surgical management.

The first consecutive 5000 patients with Coronavirus Disease 2019 from Qatar; a nation-wide cohort study.

BACKGROUND: There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). METHODS: This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU. RESULTS: Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28-43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8-68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022-1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964-9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050-2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596-8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027-1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. CONCLUSIONS: In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.

Cerebral schistosomiasis: Case series from Qatar.

Schistosomiasis is the third most widespread devastating parasitic disease worldwide and has a high mortality burden. Neuroschistosomiasis is one of the rare and most severe clinical presentations of the disease. It is caused by granuloma formation around eggs that lodge in the central nervous system, with Schistosoma japonicum usually causing most reported cerebral disease. Three unusual presentations of schistosomiasis in Qatar are described herein. The three patients were young males who presented with seizures and tumor-like lesions on brain imaging. The diagnosis was confirmed by biopsy, which showed necrotizing granulomas containing Schistosoma eggs. These cases raise awareness of neuroschistosomiasis as a potential cause of tumor-like brain lesions in migrants and returning travelers from endemic areas.