Epidemiology and clinical characteristics of Morganella morganii infections: A multicenter retrospective study.

BACKGROUND: Morganella morganii is a Gram-negative, opportunistic pathogen that can cause a variety of infections, including bloodstream infections, especially in those with compromised immune systems. It is often resistant to antibiotics, making it a difficult organism to treat. Limited studies have addressed M. morganii, but the organism is becoming increasingly recognized as a public health threat. More research is needed to understand the epidemiology and virulence factors of M. morganii in Saudi Arabia, as well as to develop effective treatment strategies. METHODS: This retrospective study included all M. morganii bloodstream infections patients admitted to five tertiary care hospitals in Saudi Arabia between 2015 and 2022. RESULTS: The study population included 75 patients (45 males and 30 females) between the age of 53-72 with a 54% ICU admission rate. The most comorbidities were hypertension followed by diabetes. The most common symptoms were fever, cough, shortness of breath, vomiting, and fatigue. The study also found that M. morganii was often resistant to multiple antibiotics, including ciprofloxacin, trimethoprim/sulfamethoxazole, gentamicin, amoxicillin, nitrofurantoin, and colistin. The most common treatment for M. morganii bacteremia was carbapenems, followed by aminoglycosides, ciprofloxacin, and colistin. Source control measures, such as surgery, line removal, drainage, and tissue removal, were also used in some cases. The study found that the in-hospital mortality rate for M. morganii bacteremia was 41%. The risk of mortality was increased in patients who were admitted to the ICU, who were older than 65 years, and who had Klebsiella pneumoniae co-infection. CONCLUSION: M. morganii bacteremia is a serious infection that is often resistant to antibiotics. Elderly patients and patients with comorbidities are at increased risk of mortality. Source control measures and appropriate antibiotic therapy are important for improving outcomes.

Outcome of Respiratory Viral Infections in Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Respiratory viral infections (RVIs) commonly cause morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. This study aimed at the prevalence of RVIs in adult HSCT recipients and their outcomes. METHODS: A retrospective observational cohort study was conducted on all adult patients who underwent HSCT in the period between January 2016 and December 2020. Data were retrospectively abstracted from electronic medical records from a total of 400 patients. All cases with polymerase chain reaction-confirmed RVIs based on real-time reverse transcription polymerase chain reaction were included in the data analysis. RESULT: A total of 79 patients had positive results. Sixty-three patients had allogeneic stem cell transplants. Women were 53% of the patients, and the mean age was 32 years (±13.5). The prevalence of documented respiratory virus infections was around 20% during the 4 years of the study. The most common virus was rhinovirus (60.76%), followed by respiratory syncytial virus (15.19%), then parainfluenza (11.39%). Among the 9 patients (11%) who required intensive care unit admission, 67% had lymphopenia (P = .03), 71% had abnormal chest computed tomography scan with pleural effusion (P = .03), 22% required renal support (P = .057), and 2 patients (22%) died (P = .057). CONCLUSIONS: The study highlights the associated morbidity and mortality with RVIs among HSCT recipients and the need for more preventive measures and treatment studies.

Case Report: COVID-19 Infection of a Transplanted Heart Simulating Cellular Rejection.

Contemporary reports showed that solid organ transplantation patients who contract SARS-CoV-2 infection have a high mortality rate. There are sparse data about recurrent cellular rejections and the immune response to the SARS-CoV-2 virus in patients after heart transplantation. Herein, we report a case of a 61-year-old male post-heart transplant patient who tested positive for COVID-19 and developed mild symptoms 4 months after transplantation. Thereafter, a series of endomyocardial biopsies showed histologic features of acute cellular rejection despite optimal immunosuppression, good cardiac functions, and hemodynamic stability. Demonstration of SARS-CoV-2 viral particles by electron microscopy in the endomyocardial biopsy confirmed the presence of the virus in the foci of the cellular rejection, pointing to a possible immunologic reaction to the virus. To our knowledge, there is limited information regarding the pathology of COVID-19 infection in immunocompromised heart transplant patients, and there are no well-established guidelines for treating such patients. Based on the demonstration of SARS-CoV-2 viral particles within the myocardium, we concluded that myocardial inflammation visible on endomyocardial biopsy might be attributed to the host's immune response to the virus, which mimics acute cellular rejection in newly heart transplanted patients. We report this case to increase awareness of such events post-transplantation and to add to knowledge regarding the management of patients with ongoing SARS-CoV-2 infection that proved to be challenging.

The clinical outcomes of COVID-19 critically ill patients co-infected with other respiratory viruses: a multicenter, cohort study.

BACKGROUND: Previous studies have shown that non-critically ill COVID-19 patients co-infected with other respiratory viruses have poor clinical outcomes. However, limited studies focused on this co-infections in critically ill patients. This study aims to evaluate the clinical outcomes of critically ill patients infected with COVID-19 and co-infected by other respiratory viruses. METHODS: A multicenter retrospective cohort study was conducted for all adult patients with COVID-19 who were hospitalized in the ICUs between March, 2020 and July, 2021. Eligible patients were sub-categorized into two groups based on simultaneous co-infection with other respiratory viruses throughout their ICU stay. Influenza A or B, Human Adenovirus (AdV), Human Coronavirus (i.e., 229E, HKU1, NL63, or OC43), Human Metapneumovirus, Human Rhinovirus/Enterovirus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Parainfluenza virus, and Respiratory Syncytial Virus (RSV) were among the respiratory viral infections screened. Patients were followed until discharge from the hospital or in-hospital death. RESULTS: A total of 836 patients were included in the final analysis. Eleven patients (1.3%) were infected concomitantly with other respiratory viruses. Rhinovirus/Enterovirus (38.5%) was the most commonly reported co-infection. No difference was observed between the two groups regarding the 30-day mortality (HR 0.39, 95% CI 0.13, 1.20; p = 0.10). The in-hospital mortality was significantly lower among co-infected patients with other respiratory viruses compared with patients who were infected with COVID-19 alone (HR 0.32 95% CI 0.10, 0.97; p = 0.04). Patients concomitantly infected with other respiratory viruses had longer median mechanical ventilation (MV) duration and hospital length of stay (LOS). CONCLUSION: Critically ill patients with COVID-19 who were concomitantly infected with other respiratory viruses had comparable 30-day mortality to those not concomitantly infected. Further proactive testing and care may be required in the case of co-infection with respiratory viruses and COVID-19. The results of our study need to be confirmed by larger studies.

Comparing Invasive Pulmonary Aspergillosis Mortality Between Liposomal Amphotericin B and Voriconazole in Patients With Hematological Malignancy or Hematopoietic Stem Cell Transplantation.

Objectives We evaluated liposomal amphotericin B versus voriconazole for the treatment of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT). Methods This retrospective cohort, single-center study included patients with compatible radiological diagnosis of IPA between 2016 and 2021. Results Forty-six patients with hematological malignancy or HSCT were diagnosed with IPA. Thirty-nine of them fulfilled the criteria for comparing liposomal amphotericin B (n=15) with voriconazole (n=24). Their median age was 48.5 years. Stem cell transplant recipients were 45.65%, and nearly half of the patients (47.83%) had acute myeloid leukemia. Twenty-six (56.52%) of the patients did not require oxygen therapy. The 12-week mortality was 13.33% (two out of 15) in patients who received liposomal amphotericin B compared to 25% (six out of 24) in patients who received voriconazole. There was no mortality judged to be related to IPA. Success or global clinical response was not different between the two drugs: 80% for liposomal amphotericin B versus 83.33% for voriconazole. However, the safety profile favored liposomal amphotericin B. Conclusion In this small cohort, there was an equipoise in the mortality and clinical and radiological outcomes obtained using liposomal amphotericin B or voriconazole for the treatment of IPA in hematological malignancy or HSCT.

Clinical characteristics and outcome of Covid-19 illness and predictors of in-hospital mortality in Saudi Arabia.

BACKGROUND: Patients' race and ethnicity may play a role in mortality from Covid-19. Studies in China, the US, and Europe have been conducted on the predictors of Covid-19 mortality, yet in the EMR countries, such studies are scarce. Therefore, we aimed to describe the hospitalization rate, ICU-admission, and in-hospital mortality of Covid-19 and predictors of in-hospital mortality in Saudi Arabia. METHODS: E-medical records were examined for all Covid-19 patients diagnosed in five tertiary hospitals affiliated with the Saudi-National Guard-Health Affairs during March 21, 2020, and September 12, 2021, based on a positive SARS-CoV-2 RT-PCR test, (n = 35,284). Data were collected on patients' characteristics, comorbidities, laboratory findings, hospitalization, ICU admission, and in-hospital and overall mortality. Logestic regressions were used to identify the independent predictors of in-hospital mortality. The best laboratory parameters cut-off values to predict in-hospital mortality were identified using the area under the receiver operating characteristic curve (AUC). Significance was considered at p < 0.05. RESULTS: Of all 35,284 Covid-19 patients, 81.8% were adults and 21.7% were hospitalized. Compared to non-hospitalized patients, hospitalized patients were more of female gender (52.1% versus 47.3%, p < 0.001) and had higher mean age (p < 0.001), higher mean BMI (p < 0.001), and higher rates of: diabetes (p < 0.001), hypertension (p < 0.001), ischemic heart disease (p < 0.001), cancer (p < 0.001), COPD (p < 0.001) and asthma (p = 0.011). The study showed 3.1% overall case-fatality, 20.3% ICU admission rate, and 9.7% in-hospital mortality. Predictors of in-hospital mortality among adult patients were; patients' age ≥ 70 years (OR = 6.93, 95% CI 1.94-24.79), ischemic heart disease (OR = 1.80, 95% CI 1.05-3.09), ICU admission (OR = 24.38, 95% CI 15.64-38.01), abnormal C-reactive protein "CRP" (OR = 1.85, 95% CI 1.08-3.16), abnormal D-dimer (OR = 1.96, 95% CI 1.15-3.36), lymphopenia (OR = 2.76, 95% CI 2.03-3.3.76), high neutrophil count (OR = 2.10, 95% CI 1.54-2.87), and abnormal procalcitonin (OR = 3.33, 95% CI 1.88-5.90). The best laboratory parameters cut-off values to predict in-hospital mortality were CRP > 72.25 mg/L (AUC = 0.64), D-dimer > 1125 µg/L (AUC = 0.75), neutrophils count > 5,745 × 10^9/L (AUC = 0.70), lymphocytic count < 1.10 × 10^9/L (AUC = 0.72), and procalcitonin > 0.18 ng/mL (AUC = 0.76). CONCLUSIONS: Rates of hospitalization, ICU-admission, in-hospital mortality and overall case fatality were nearly comparable to the rates in western countries. Early interventions are necessary for high-risk Covid-19 patients, especially elderly patients and those with cardiac diseases.

Risk factors of SARS-CoV-2 infection in cancer patients pre- and post-vaccination.

BACKGROUND: Severe complications from COVID-19 and poor responses to SARS-CoV-2 vaccination were commonly reported in cancer patients compared to those without cancer. Therefore, the identification of predisposing factors to SARS-CoV-2 infection in cancer patients would assist in the prevention of COVID-19 and improve vaccination strategies. The literature lacks reports on this topic from the Kingdom of Saudi Arabia (KSA). Therefore, we studied clinical and laboratory data of 139 cancer patients from King Abdulaziz Medical City, Riyadh, KSA. METHODS: The cancer patients fall into three categories; (i) uninfected with SARS-CoV-2 pre-vaccination and remained uninfected post-vaccination (control group; n = 114; 81%), (ii) pre-vaccination infected group (n = 16; 11%), or (iii) post-vaccination infected group (n = 9; 6%). Next, the clinical and lab data of the three groups of patients were investigated. RESULTS: Comorbidity factors like diabetes and hemodialysis were associated with the risk of infection in cancer patients before the vaccination (p<0.05). In contrast to breast cancer, papillary thyroid cancer was more prevalent in the infected patients pre- and post-vaccination (p<0.05). Pre-vaccination infected group had earlier cancer stages compared with the control group (p = 0.01). On the other hand, combined therapy was less commonly administrated to the infected groups versus the control group (p<0.05). Neutrophil to lymphocyte ratio was lower in the post-vaccination infected group compared to the control group (p = 0.01). CONCLUSION: Collectively, this is the first study from KSA to report potential risk factors of SARS-CoV-2 infection in cancer patients pre- and post-vaccination. Further investigations on these risk factors in a larger cohort are worthwhile to draw a definitive conclusion about their roles in predisposing cancer patients to the infection.

Successful heart transplantation from a donor with bacterial and fungal bloodstream infection: Case report of donor optimization strategy.

Donor optimization is vital to increase donor hearts utilized for transplantation. We report a case of a 34-year-old female with end-stage cardiomyopathy that was admitted to the intensive care unit on inotropic support with progressive decline (INTERMACS-2). She was offered a donor heart from a 14-year male that was found to have Klebsiella pneumoniae bacteremia and candidemia co-infection. The donor was transferred to our hospital and optimized hemodynamically and biochemically. Targeted antimicrobial and antifungal therapy based on the susceptibility testing was established in the donor till blood cultures were negative. The recipient received similar prophylactic therapy for 2-week course starting 24-h before transplantation. The patient was transplanted with no clinical consequences. She was discharged home in 4 weeks post-transplantation. Her 3-month follow-up was completely uneventful.

A Trial of Favipiravir and Hydroxychloroquine combination in Adults Hospitalized with moderate and severe Covid-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. TRIAL DESIGN: This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. PARTICIPANTS: All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. INTERVENTION AND COMPARATOR: The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . MAIN OUTCOMES: The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). RANDOMISATION: Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. BLINDING (MASKING): This is an Open label study and only the analyst will be blinded during the study conduct. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). TRIAL STATUS: Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04392973 , 19 May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Optimal pre-emptive cytomegalovirus therapy threshold in a patient population with high prevalence of seropositive status.

INTRODUCTION: Preemptive therapy (PET) for cytomegalovirus (CMV) reactivation post allogeneic hematopoietic stem cell transplantation (SCT) was shown to decrease the incidence of CMV disease. However, the optimal PET threshold is elusive. PURPOSE OF THE STUDY: To examine the efficacy of PET initiation at a viral threshold of 1000 copies/mL (1560 IU/mL) in a patient population with high prevalence of CMV seropositive status. PATIENTS AND METHODS: A single center retrospective review of patients that underwent allogeneic SCT was done. RESULTS: A total of 195 allogeneic SCT recipients were included with median follow up of 18.1 (0.7-95.6) months. A total of 178 (91 %) of patients had a positive CMV PCR with median days to initial reactivation post SCT of 17 (1-1187); 129 patients had peak CMV titer < 1000 copies/mL (low titer) whereas the remaining 49 patients had a peak titer ≥ 1000 copies/mL (high titer). 120 (93 %) of patients with low titers cleared spontaneously with median time to clearance of 40 days (4-188). One patient in the high titer group developed CMV disease. At multivariable analysis; age at SCT HR 1.02 (1.004-1.04; 0.017), malignant vs. benign condition HR 9.4 (2.47-61; 0.0005) and cGVHD HR 0.37 (0.2-0.65; 0.0005) were significant for OS. CONCLUSIONS: CMV reactivation post SCT was very common in patients with high prevalence of seropositive status. A PET threshold of 1000 copies/mL (1560 IU/mL) appears desirable as it was associated with spontaneous clearance in over 90 % of patients while minimizing treatment related toxicity. Validation of these observations is warranted.

Seasonal influenza vaccine in immunocompromised persons.

Immunocompromised persons are at high risk of complications from influenza infection. This population includes those with solid organ transplants, hematopoietic stem cell transplants, solid cancers and hematologic malignancy as well as those with autoimmune conditions receiving biologic therapies. In this review, we discuss the impact of influenza infection and evidence for vaccine effectiveness and immunogenicity. Overall, lower respiratory disease from influenza is common; however, vaccine immunogenicity is low. Despite this, in some populations, influenza vaccine has demonstrated effectiveness in reducing severe disease. Various strategies to improve influenza vaccine immunogenicity have been attempted including two vaccine doses in the same influenza season, intradermal, adjuvanted, and high-dose vaccines. The timing of influenza vaccine is also important to achieve optimal immunogenicity. Given the suboptimal immunogenicity, family members and healthcare professionals involved in the care of these populations should be vaccinated. Health care professional recommendation for vaccination is an important factor in vaccine coverage.