Posaconazole versus voriconazole as antifungal prophylaxis for invasive fungal diseases in patients with hematological malignancies.

INTRODUCTION: The incidence of invasive fungal diseases (IFDs) has risen in hematologic malignancy patients due to neutropenia. While posaconazole is recommended as the first-line antifungal prophylaxis in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients and voriconazole is an alternative, there is currently no direct comparison data available to assess their relative effectiveness. METHOD: We retrospectively reviewed eligible patient charts from January 2017 to February 2019 to identify breakthrough IFD rates, drug adverse event frequency, and drug acquisition cost in AML/MDS patients. RESULTS: Forty-eight patients received 130 chemo cycles, with 50 (38%) cycles prescribed posaconazole and 80 (62%) prescribed voriconazole as primary IFD prophylaxis. The incidence rates of IFD in the posaconazole group were 8% (4 out of 50), of which two were probable and two were possible infections, while 6.26% (5 out of 80) of patients in the voriconazole group developed IFD, with four possible infections and one probable infection (p = 0.73). A higher percentage of patients in the voriconazole group discontinued prophylaxis due to adverse events, with six patients compared to two patients in the posaconazole group (p = 0.15). The drug acquisition cost of posaconazole is 5.62 times more expensive than voriconazole. CONCLUSION: The use of voriconazole instead of posaconazole for 130 chemo cycles would save $166,584.6. Posaconazole and voriconazole have comparable efficacy and safety in preventing IFD in AML and MDS patients receiving chemotherapy. However, posaconazole is more costly than voriconazole.

The predictors and risk factors of two-year rejection in renal transplant patients: A multicenter case-control study.

INTRODUCTION: Kidney transplantation is a definitive treatment for end-stage renal disease. It is associated with improved life expectancy and quality of life. One of the most common complications following kidney transplantation is graft rejection. To our knowledge, no previous study has identified rejection risk factors in kidney transplant recipients in Saudi Arabia. Therefore, the purpose of this study was to determine the specific risk factors of graft rejection. METHODS: A multicenter case-control study was conducted at four transplant centers in Saudi Arabia. All adult patients who underwent a renal transplant in the period between 01/01/2015 and 31/12/2021 were screened for eligibility. Included patients were categorized into two groups (cases and control) based on the occurrence of biopsy-proven rejection within two years. The primary outcome was to determine the risk factors for rejection within the first two years of transplant. Exact matching was utilized using a 1:4 ratio based on patients' age, gender, and transplant year. RESULTS: Out of 1320 screened renal transplant recipients, 816 patients were included. The overall prevalence of two-year rejection was 13.9%. In bivariate analysis, deceased donor status, the presence Donor Specific Antibody (DSA), intraoperative hypotension, serum Chloride levels, Pseudomonas aeruginosa, Candida, and any Infection within two years were linked with increased risk of two-year rejection. However, in the logistic regression analysis, DSA was identified as a significant risk for two-year rejection (Adjusted OR 2.68; 95% CI, 1.10, 6.49, p = 0.03). While, the presence of Panel-reactive antibody (PRA) and higher serum chloride levels one week prior to transplant was associated with lower odds of rejection (Adjusted OR 0.12; 95% CI, 0.03, 0.53, p = 0.005 and Adjusted OR 0.93; 95% CI, 0.86, 0.98, p = 0.02, respectively). Furthermore, blood infection, infected with Pseudomonas aeruginosa or BK virus within two years of transplant was associated with higher odds of two-year rejection (Adjusted OR 3.10; 95% CI, 1.48, 6.48, p = 0.003, Adjusted OR 3.23; 95% CI, 0.87, 11.97, p = 0.08 and Adjusted OR 2.76; 95% CI, 0.89, 8.48, p = 0.07, respectively). CONCLUSION: Our findings emphasize the need for appropriate prevention and management of infections following kidney transplantation to avoid more serious problems, such as rejection, which could significantly raise the likelihood of allograft failure and probably death. Further studies with larger sample size are needed to investigate the impact of serum chloride levels prior to transplant and intraoperative hypotension on the risk of rejection.

Risk factors, antifungal susceptibility, complications, and outcome of Candida auris bloodstream infection in a tertiary care center in the western region of Saudi Arabia.

BACKGROUND: Candida auris, an emerging multidrug-resistant fungus species that grows as yeast, causes bloodstream infection, and is associated with high mortality rates. In this study, we identified risk factors associated with C. auris bloodstream infection, antifungal susceptibility pattern, complications, and outcome of the infection. METHODS: This single-center cross-sectional retrospective study was conducted at King Abdulaziz Medical City, a tertiary care facility in Jeddah, Saudi Arabia, which included all patients 18 years or above who have had one or more blood cultures for C. auris between January 2021 and December 2022. We aimed to identify the risk factors associated with C. auris bloodstream infection, antifungal susceptibility patterns, complications, and outcomes at our center. RESULTS: Forty-six patients with C. auris-positive blood cultures were included. All the patients had healthcare-associated infections. The mean age was 64.67 years, and the majority of patients were male (73.9 %). The most common concomitant hospital-acquired infections were skin and soft tissue infections (37 %), followed by hospital-acquired pneumonia (34.8 %) and intra-abdominal infections (26.1 %). The mean total white blood cell count, procalcitonin, and C-reactive protein was 10.5 ± 5.99 × 109/L, 2.63 ± 4.82 µg/L, and 90.3 ± 64.1 mg/L, respectively. Hypertension (73.9 %) was the most common comorbidity, followed by diabetes mellitus (58.7 %) and renal dysfunction (54.3 %). Risk factors associated with C. auris candidemia included antibiotic use (91.3 %), especially for > 14 days (78.3 %), C. auris colonization (60.9 %), use of central venous catheters, especially when the catheter was in place for >30 days (80.4 %), ICU admission in the last 30 days before C. auris-positive blood culture (93.5 %), especially for more than two weeks (76.1 %), mechanical ventilation (89.1 %), total parenteral nutrition (13 %), previous intra-abdominal surgery (30.4 %), and immunosuppressive therapy (56.5 %). A total of 97.8 % of C. auris isolates were resistant to fluconazole and 17.4 % were resistant to amphotericin B. Endocarditis and endophthalmitis were reported in one (2.2 %) patient each. The all-cause mortality at 30 days was 47.8 %. CONCLUSION: Our study is one of the few studies available globally on C. auris bloodstream infection that investigated risk factors, antifungal susceptibility, complications, and outcomes. A thorough screening and risk assessment strategy should aid infection control, preventing it from becoming a major concern in the future.

Microbiological and Clinical Outcomes of Methicillin-Susceptible Staphylococcus aureus Isolated in Lung Transplant Perioperative Donor and Recipient Respiratory Cultures.

Staphylococcus aureus is one of the most common organisms isolated from respiratory secretions in lung transplant donors and recipients perioperatively. Within the first 90 days after lung transplantation, methicillin-susceptible Staphylococcus aureus (MSSA) infections have been associated with increased mortality and acute and chronic rejection. However, it is unclear whether respiratory cultures positive for MSSA at the time of transplantation can lead to clinically significant infection. The aim of this study was to assess the microbiological and clinical outcomes for lung transplant recipients (LTRs) with positive perioperative donor or/and recipient respiratory cultures for MSSA. A retrospective study was conducted evaluating MSSA-positive respiratory cultures at the time of lung transplantation from donors and/or recipients from January 1, 2008, to December 30, 2019. Patients who did not have a bronchoalveolar lavage at 2 weeks after the lung transplant or died within 2 weeks of lung transplant were excluded. The main outcome was MSSA eradication at 2-week bronchoscopy. Recipients were evaluated for MSSA infections at the 12-week period after the transplant. Of the 1,678 individuals who underwent lung transplantation, 218 LTRs had S. aureus isolated in perioperative donor or recipient respiratory cultures, and 29 were subsequently excluded. Of the remaining 189 LTRs, MSSA eradication at the 2-week bronchoscopy was achieved in 186 (98.4%) recipients. During the 12-week follow-up, 15 (7.9%) recipients were diagnosed with MSSA pneumonia; concurrent MSSA bacteremia was noted in one recipient. No anastomotic infection, empyema, or lung abscess related to MSSA was diagnosed during the follow-up period.In LTRs, the rate of MSSA eradication at 2-week post-transplant recipients is high, and it is associated with a low rate of infectious complication within the first 12 weeks after transplant. Most of the recipients received a combination therapy with at least one agent active against MSSA. More studies to evaluate the optimal antimicrobial stewardship policies regarding the regimen and duration of antibiotic therapy for these patients are needed.

Invasive mucormycosis in a tertiary care hospital in the western region of Saudi Arabia: 11-year retrospective chart review from 2009 to 2019.

BACKGROUND: Mucormycosis is a life-threatening, invasive fungal disease that mostly affects immunocompromised hosts. In this study, we aimed to assess the clinical presentations and outcomes of patients with mucormycosis in a tertiary care hospital in the western region of Saudi Arabia. METHODS: A retrospective chart review of patients diagnosed with mucormycosis was conducted from January 2009 to December 2019 at King Abdulaziz Medical City, a tertiary care facility in Jeddah, Saudi Arabia. We aimed to assess and analyze the characteristics of patients with mucormycosis, their clinical presentations, and treatment outcomes. RESULTS: Fifteen cases were identified as proven or probable mucormycosis according to the revised European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Most cases (n = 11, 73.3 %) were categorized as proven, whereas four cases (26.7 %) were categorized as probable. The median patient age was 29.5 years (range, 6-79 years). The most common underlying etiology was hematological malignancies (7 cases), followed by diabetes mellitus (5 cases), and trauma from a motor vehicle accident (4 cases). Cutaneous mucormycosis was the predominant presentation, as noted in seven cases (46.6 %), followed by rhino-orbito-cerebral mucormycosis in four cases (26.7 %), and pulmonary mucormycosis in two cases (13.3 %). Rhizopus (six cases) and Mucor (four cases) were the two main fungal isolates. Eight patients were treated with amphotericin B lipid complex (53.3 %) alone, and three patients were treated with a combination of amphotericin B lipid complex and posaconazole. Overall, 11 (73.3 %) patients died, two of whom died before a confirmed diagnosis. CONCLUSION: The mortality among patients with mucormycosis was high. Relatively better survival was observed among cutaneous cases. A combination of new diagnostic technologies, optimized use of available antifungal options, development of new antifungal agents, and consistent implementation of public health policies may help reduce mortality rates from mucormycosis in Saudi Arabia.

The prevalence, risk factors, and complications of Clostridium difficile infection in a tertiary care center, western region, Saudi Arabia.

BACKGROUND: Clostridium difficile is an anaerobic gram-positive spore-forming bacillus that is most commonly associated with nosocomial diarrhea. This study aimed to analyze the prevalence and risk factors of Clostridium difficile infection (CDI) at a tertiary health care center, Western region, Saudi Arabia. We also aimed to examine the duration of exposure to each risk factor prior CDI development, and to categorize CDI as severe and non-severe depending on the white blood cell (WBC) count. Various complications of the infection were also analyzed. METHODS: We performed a retrospective chart review of all patients who had a positive nucleic acid amplification test (NAAT) for Clostridium difficile toxin genes between October 2018 and October 2020. RESULTS: The prevalence of CDI among the included patients was 9.1% (237 of 2611 patients). The mean age (standard deviation) was 56.86 (21) years, and the infection was more prevalent among men (52.74%) than among women (47.26%). The most common risk factor associated with CDI was recent antibiotic use (74.68%), followed by recent acid suppressant use (67.50%), malignancy (46%), and previous gastrointestinal surgery (6.30%). The CDI recurrence rate was 13.90%. Piperacillin-tazobactam was the most frequently used broad-spectrum antibiotic, and was used in 38.8% of the patients, followed by meropenem. The most common malignancy type was lymphoma (22.94%, n = 25), followed by leukemia (n = 23). The most common type of surgery was subtotal colectomy (n = 6). Three patients underwent transverse colon resection, and two underwent ileocecal resection. Hypotension was the most frequently recorded complication (28.40%) in the study population. CONCLUSION: The prevalence rate of CDI among the study patients during the two-year study from October 2018 to October 2020 was 9.1%. Appropriate use of antibiotic and acid suppressants, and contact isolation measures can help in decreasing the number of CDI cases.

Melioidosis Pneumonia in Saudi Arabia: A Rare Case Report and Review of the Literature.

Melioidosis is a serious infection caused by the bacterium Burkholderia pseudomallei (B. pseudomallei) mostly found in endemic areas like Southeast Asia and Northern Australia. However, in non-endemic regions, such as Saudi Arabia, it remains somewhat rare and unknown to healthcare workers and the public. Herein, we present a case of melioidosis in a 59-year-old Bangladeshi man who presented with pneumonia. He recently returned from Bangladesh, was a known case of type 2 diabetes on metformin, and presented to the emergency department (ED) with a history of cough, shortness of breath, and fever for three weeks. He was initially misdiagnosed and treated as pulmonary tuberculosis in another hospital prior to his latest presentation. Melioidosis is a severe infection that can be misdiagnosed due to variable presentation and low awareness among healthcare workers of the disease. Diagnosis requires high clinical suspicion, especially in patients who are coming from endemic areas with appropriate risk factors such as diabetes mellitus. Treatment with appropriate antibiotics for a long duration, and outpatient follow-up is vital to reduce the risk of recurrence.

Simultaneous Occurrence of Cytomegalovirus Colitis and Retinitis as the Initial Presentation of Human Immunodeficiency Virus Infection in a Patient With Zero CD4 Count.

Cytomegalovirus (CMV) can be a reason for severe disease in immunocompromised patients, either via the reactivation of latent CMV infection or via the acquisition of primary CMV infection. Clinical syndromes that may be observed are retinitis, colitis, esophagitis, encephalitis, pneumonitis, hepatitis, uveitis, and graft rejection following transplantation. The simultaneous occurrence of CMV colitis and retinitis as the initial presentation of human immunodeficiency virus (HIV) infection is extremely rare. We present a case of a 42-year-old male, known to have type 2 diabetes, bronchial asthma, and allergic rhinitis, who presented to the emergency department (ED) with two weeks history of abdominal pain and watery diarrhea four to five times per day sometimes accompanied by small amounts of blood. He also had an on-and-off subjective fever for the last two months prior to presentation, loss of appetite, and weight loss of 13 kg over the last six months. Additionally, he had a history of travel outside Saudi Arabia and unprotected sex. HIV-1 serology (combination antigen/antibody immunoassay) was requested, which came out positive, with a viral load of 323141 copies/mL and decreased CD4+ T lymphocytes (0 cel/µL). CMV polymerase chain reaction (PCR) quantitative was detected and the CMV viral load was 694963 IU/mL. Given the patient's bloody diarrhea with positive CMV and HIV, the gastroenterology team was consulted and they decided to proceed with a colonoscopy and biopsy. The patient was diagnosed with CMV colitis based on the biopsy results. The patient also was found to have CMV retinitis based on ophthalmologic assessment. Multidisciplinary teams, including infectious diseases, gastroenterology, ophthalmology, and pathology, should cooperate to facilitate an accurate and fast diagnosis. Further complications can be prevented by early diagnosis andtreatment.

Electronic early notification of sepsis in hospitalized ward patients: a study protocol for a stepped-wedge cluster randomized controlled trial.

BACKGROUND: To evaluate the effect of screening for sepsis using an electronic sepsis alert vs. no alert in hospitalized ward patients on 90-day in-hospital mortality. METHODS: The SCREEN trial is designed as a stepped-wedge cluster randomized controlled trial. Hospital wards (total of 45 wards, constituting clusters in this design) are randomized to have active alert vs. masked alert, 5 wards at a time, with each 5 wards constituting a sequence. The study consists of ten 2-month periods with a phased introduction of the intervention. In the first period, all wards have a masked alert for 2 months. Afterwards the intervention (alert system) is implemented in a new sequence every 2-month period until the intervention is implemented in all sequences. The intervention includes the implementation of an electronic alert system developed in the hospital electronic medical records based on the quick sequential organ failure assessment (qSOFA). The alert system sends notifications of "possible sepsis alert" to the bedside nurse, charge nurse, and primary medical team and requires an acknowledgment in the health information system from the bedside nurse and physician. The calculated sample size is 65,250. The primary endpoint is in-hospital mortality by 90 days. DISCUSSION: The trial started on October 1, 2019, and is expected to complete patient follow-up by the end of October 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT04078594 . Registered on September 6, 2019.

Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial.

INTRODUCTION: Antiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients. METHODS: An investigator-initiated, multicenter, open-label, randomized trial at nine hospitals. Eligible patients were adults with moderate-to-severe COVID-19 defined as oxygen saturation (SaO2) of ≤ 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes requiring hospital admission. Randomization was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The primary outcome was time to clinical improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population. RESULTS: From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 to the treatment. The mean age was 52 (± 13) years, and 103 (41%) were women. At randomization, six patients were on invasive mechanical ventilation, 229 (90.15%) were requiring supplemental oxygen only (with or without non-invasive ventilation), and 19 (7.48%) were receiving neither. The time to clinical improvement was not significantly different between the groups: median of 9 days in the treatment group and 7 days in the control group (HR: 0.845; 95% CI 0.617-1.157; p-value = 0.29). The 28-day mortality was not significantly different between the groups (7.63% treatment) vs. (10.32% control); p-value = 0.45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group. CONCLUSION: The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04392973).

Symptomatic BK virus cystitis in non-renal transplant recipients.

Background: BK virus is implicated most commonly in causing BK virus-associated nephropathy in renal transplant recipients. However, on rare occasions, it can also produce symptomatic cystitis in other solid organ transplant recipients. Methods: Retrospective review of 2,149 non-renal solid organ transplant recipients over a 6-year period to evaluate patients for cases of symptomatic BK virus cystitis. Results: Three patients (two heart transplant recipients and one lung transplant recipient) are reported herein with symptomatic BK virus cystitis. These patients responded to reduced immunosuppressive medication with a reduction in viral load in two instances, and the third patient appeared to have an apparent response to prolonged levofloxacin treatment. Conclusions: A high index of suspicion should be exercised in non-renal solid organ transplant recipients (particularly heart and lung transplant recipients) who have symptoms consistent with cystitis but have a negative urine bacterial culture.

Historique: Le virus BK s'associe surtout à des néphropathies chez les greffés du rein. Cependant, en de rares occasions, il peut provoquer une cystite chez d'autres greffés d'organes pleins. Méthodologie: Analyse rétrospective de 2 149 greffés d'un autre organe plein que le rein sur une période de six ans pour évaluer les cas de cystite symptomatique à virus BK. Résultats: Les auteurs rendent compte de trois patients (deux greffés du cœur et un greffé du poumon) atteints d'une cystite symptomatique à virus BK. Deux patients ont répondu à une dose réduite d'immunosuppresseur par une diminution de leur charge virale, et le troisième semble avoir présenté une réponse apparente à un traitement prolongé à la lévofloxacine. Conclusions: Il faut avoir un fort indice de suspicion chez les greffés d'un autre organe plein que le rein (particulièrement les greffés du cœur et du poumon) qui ont des symptômes évocateurs de cystite, mais une culture bactérienne négative des urines.