An Emerging Issue: Carbapenem-Resistant Enterobacteriaceae in Solid-Organ Transplantation.

OBJECTIVES: Bloodstream infections caused by carbapenem-resistant bacteria have increased globally. Solid-organ transplant recipients are more prone to these infections. This study aimed to compare the clinical courses of carbapenem-susceptible and carbapenem-resistant Enterobacteriaceae bloodstream infections and to identify risk factors for carbapenem resistance in solid-organ transplant recipients. MATERIALS AND METHODS: For this retrospective descriptive study, data for solid-organ transplant recipients (age ≥18) treated from 2015 to 2022 were obtained from medical records. Enterobacteriaceaepositive blood culture was screened from laboratory data. RESULTS: Among 72 patients, there were 100 bacteremia episodes. Patients included 40 kidney (55.6%), 21 liver (29.2%), 7 heart (9.7%), and 4 combined liver and kidney (5.6%) transplant recipients. Fifty-seven bacteremia episodes were recorded between 2015 and 2020, and 43 bacteremia episodes were recorded between 2020 and 2022. Carbapenem resistance was reported in 15.8% of patients before 2020, whereas this rate increased to 39.5% after 2020 (P = .007). Pitt bacteremia score ≥4 (P < .001), Charlson comorbidity index ≥4 (P = .021), chronic liver disease (P = .015), septic shock at admission (P = .001), hypotension at admission (P = .006), bacteremia episodes 48 hours after hospitalization (P = .004), hospitalization in the past 3 months (P = .004), and prior invasive procedure (P = .043) were significant factors for carbapenem resistance. Logistic regression analysis showed that bacteremia 48 hours after hospitalization (P = .002) and hospitalization in the past 3 months (P = .006) were independent risk factors. CONCLUSIONS: Carbapenem resistance increased significantly over the years. Bacteremia 48 hours after hospitalization and hospitalization within the past 3 months were determined to be risk factors for carbapenem resistance. Carbapenem-resistant infections are still nosocomial infections. Patients should be hospitalized for as a short time as possible, and both patients and their physicians should follow infection control and prevention methods.

Evaluation of Candidemia in Solid-Organ Transplant Recipients.

OBJECTIVES: Solid-organ transplant recipients have high rates of invasive fungal infections. Candida species are the most commonly isolated fungi. Our aim was to identify risk factors, clinical presentations, and outcomes of candidemia in solid-organ transplant recipients. MATERIALS AND METHODS: We evaluated adult (≥18 years old) transplant recipients seen from May 2011 to December 2022 at Baskent University Ankara Hospital. From medical records, we retrospectively reviewed age, sex, transplant type, candidemia agent, risk factors, concomitant infections, and mortality of patients with Candida detected in blood culture. We used SPSS statistics software (version 25) to analyze data. RESULTS: There were 1080 organ transplants performed during the study period (717 kidney, 279 liver, 84 heart). There were 855 who were ≥18 years (655 kidney, 127 liver, 73 heart), of whom candidemia was detected in 26 (16 male; 11 kidney, 11 liver, 4 heart) with a median age of 47.5 years. The most common agents were Candida albicans and Candida glabrata. The most common chronic diseases were hypertension, cirrhosis, and cardiomyopathy. Eighteen patients had a concomitant focus of infection. Ten patients had pneumonia accompanying candidemia. The 30-day mortality rate was as high as 53.8%. The mean duration of candidemia after transplant was 23 months. Catheter-related candidemia was observed in 65% of patients. The 30-day mortality was found to be significantly higher in patients followed in the intensive care unit (P = .014), receiving total parenteral nutrition (P = .001), using broad-spectrum antibiotics (P = .001), and having pneumonia (P = .042) accompanying candidemia. CONCLUSIONS: For adult solid-organ transplant recipients with candidemia, careful monitoring is essential for successful management of total parenteral nutrition, central catheter, use of broadspectrum antibiotics, and invasive interventions.

Herpes Zoster Infections in Solid-Organ Transplant Recipients.

OBJECTIVES: Herpes zoster infections can be complicated and mortal in solid-organ transplant recipients. In our study, we investigated herpes zoster infections in solid-organ transplant recipients. MATERIALS AND METHODS: UntilJune 2022, our center has performed 3342 kidney, 708 liver, and 148 heart transplants.Herpes zosterinfections were investigated in 1050 adult solid-organ transplant recipients from January 1, 2011, to June 31, 2022. We studied 44 patients diagnosed with herpes zoster infections. RESULTS: Of the 44 patients with herpes zoster, 32 had kidney, 7 had heart, and 5 had liver transplant procedures. Crude incidence rate was 5.2%.,with 9.7% being heart, 5.1% being kidney, and 3.9% being liver transplant recipients; 72.7% were male patients. The median age was 47.5 years, and 61% of patients were aged >45 years. Postherpetic neuralgia was significantly higher in patients older than 45 years (P = .006). The median duration to infection posttransplant was 16.5 months. The dermatomes of patients were 43.2% thoracic. Sacral dermatome involvement was significantly higher in heart transplant patients than in other transplant recipients (P = .015). We reviewed specific findings of the Tzanck test in 36.4% of the patients. There was concomitant infection in 15.9% of the patients, and 6.8% had pneumonia. Acute neuritis was more common in kidney transplant recipients (65.6%). The mean duration of acute neuritis/neuralgia was longest in liver transplant recipients (13.5 months; P = .047). Postherpetic neuralgia was detected as high as 24%. CONCLUSIONS: Early specific and supportive treatmentis important for transplant recipients with herpes zoster infections. Appropriate antiviral prophylaxis regimens and vaccination strategies for varicella zoster (chickenpox) and herpes zoster infections should be implemented in the vaccination schedule of solidorgan transplant candidates to prevent herpes zoster infections and complications.

Ophthalmologic Examination and Echocardiography Should be the Essential Components of Candidemia Bundle.

Objective: Candidemia is the most common form of invasive candidiasis, and it is associated with end-organ involvement, prolonged hospitalization, increased mortality, and higher healthcare costs. Candidemia can lead to metastatic heart and ocular infections. This study aimed to define the incidence, characteristics, and mortality of candidemia episodes and compare the data with our center's previous results. Materials and Methods: In this single-center retrospective observational study, we enrolled 250 patients over 18 years diagnosed with candidemia between January 2015 and December 2020. We obtained patients' demographic, clinical, laboratory, and therapeutic data from medical records. An ophthalmologic examination and screening with echocardiography were carried out within the first week after candidemia diagnosis. Results: There were 275 candidemia episodes from 250 patients. The incidence of candidemia was 2.8/1000 admissions and 5.68/ 10,000 inpatient days, higher than our previous results (1.23/1000 and 3.29/10,000). The median age was 65 (interquartile range [IQR]=52-75) years. Malignancies were the most frequent comorbidity (50%). The most common type was Candida albicans (n=115, 41.8%). Candida glabrata (n=61, 22.2%) was common, particularly in surgical patients, patients with malignancy, and critically ill patients. There was Infectious disease consultation in 93.3% (257) episodes.The ophthalmoscopic examination was made in 145 episodes (52.7%), and ophthalmitis was detected in 16 (11.0%). Echocardiography was performed in 139 (50.5%) episodes; one case had an endocarditis diagnosis. The 30-day mortality was 44.7% (n=123). Mortality rates in C. glabrata and Candida krusei infections were higher (54.1% and 66.7). The factors related to mortality were intensive care unit requirement (p=0.0001), chronic liver disease (p=0.005), corticosteroid usage (p=0.0001), previous antibiotic usage (p=0.013), multiple antibiotic usage ( p=0.020), and CVC related candidemia (p=0.010). Conclusion: Because of the life-threatening complications such as endocarditis, increased mortality rates, and higher healthcare costs, systematic and comprehensive candidemia bundle applications would be effective strategies for providing an effective antifungal stewardship program.

Detection of COVID-19 by Machine Learning Using Routine Laboratory Tests.

OBJECTIVES: The present study aimed to develop a clinical decision support tool to assist coronavirus disease 2019 (COVID-19) diagnoses with machine learning (ML) models using routine laboratory test results. METHODS: We developed ML models using laboratory data (n = 1,391) composed of six clinical chemistry (CC) results, 14 CBC parameter results, and results of a severe acute respiratory syndrome coronavirus 2 real-time reverse transcription-polymerase chain reaction as a gold standard method. Four ML algorithms, including random forest (RF), gradient boosting (XGBoost), support vector machine (SVM), and logistic regression, were used to build eight ML models using CBC and a combination of CC and CBC parameters. Performance evaluation was conducted on the test data set and external validation data set from Brazil. RESULTS: The accuracy values of all models ranged from 74% to 91%. The RF model trained from CC and CBC analytes showed the best performance on the present study's data set (accuracy, 85.3%; sensitivity, 79.6%; specificity, 91.2%). The RF model trained from only CBC parameters detected COVID-19 cases with 82.8% accuracy. The best performance on the external validation data set belonged to the SVM model trained from CC and CBC parameters (accuracy, 91.18%; sensitivity, 100%; specificity, 84.21%). CONCLUSIONS: ML models presented in this study can be used as clinical decision support tools to contribute to physicians' clinical judgment for COVID-19 diagnoses.

Immunogenicity after two doses of inactivated virus vaccine in healthcare workers with and without previous COVID-19 infection: Prospective observational study.

Vaccines have been seen as the most important solution for ending the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate the antibody levels after inactivated virus vaccination. We included 148 healthcare workers (74 with prior COVID-19 infection and 74 with not). They received two doses of inactivated virus vaccine (CoronaVac). Serum samples were prospectively collected three times (Days 0, 28, 56). We measured SARS-CoV-2 IgGsp antibodies quantitatively and neutralizing antibodies. After the first dose, antibody responses did not develop in 64.8% of the participants without prior COVID-19 infection. All participants had developed antibody responses after the second dose. We observed that IgGsp antibody titers elicited by a single vaccine dose in participants with prior COVID-19 infection were higher than after two doses of vaccine in participants without prior infection (geometric mean titer: 898 and 607 AU/ml). IgGsp antibodies, participants with prior COVID-19 infection had higher antibody levels as geometric mean titers at all time points (p < 0.001). We also found a positive correlation between IgGsp antibody titers and neutralizing capacity (rs = 0.697, p < 0.001). Although people without prior COVID-19 infection should complete their vaccination protocol, the adequacy of a single dose of vaccine is still in question for individuals with prior COVID-19. New methods are needed to measure the duration of protection of vaccines and their effectiveness against variants as the world is vaccinated. We believe quantitative IgGsp values may reflect the neutralization capacity of some vaccines.

Differences in Antibody Responses Between an Inactivated SARS-CoV-2 Vaccine and the BNT162b2 mRNA Vaccine in Solid-Organ Transplant Recipients.

OBJECTIVES: Vaccination against SARS-CoV-2 may reduce COVID-19 mortality and complications in solidorgan transplant recipients, and we evaluated the associated antibody responses and adverse effects in this high-risk population. MATERIALS AND METHODS: This prospective observational study (April-June 2021) included 10 liver and 38 kidney transplant recipients who received 2 vaccine doses (Sinovac, n = 31; or BioNTech, n = 17) and 56 healthy adults (Sinovac), all of whom provided 3 blood samples (prevaccination, 4 weeks after first dose, and 4-6 weeks after second dose) for quantitative tests (Abbott Quant assay forimmunoglobulin G antibodies against SARS-CoV-2 spike protein). Type I error was α = .05 in all statistical analyses (SPSS, version 25). RESULTS: We analyzed demographic data, antibody responses, and adverse events after 2 doses of SARSCoV-2 vaccine, comparedimmune responses from solidorgan transplant recipients (median age, 36.5 years) versus healthy patients (median age, 37.5 years), and observed significantly higher seropositivity in healthy versus transplant patients after Sinovac vaccination (100% vs 67.5%; P = .001). However, we observed no significant seropositive differences for Sinovac versus BioNTech second doses in transplantrecipients. Median SARS-CoV-2 immunoglobulin G level after second dose was significantly higher in BioNTech (1388.6 AU/mL) versus Sinovac patients (136.6 AU/mL) (P = .012). The seropositivity difference between the 2 vaccines was significant in participants 24 to 44 years old (P = .040). The rate of at least 1 side effect was 82.4% (n = 14) for BioNTech vaccine and 32.3% (n = 10) for Sinovac vaccine, and the difference was statistically significant.The most common side effect was arm pain (significantly higher in BioNTech group). CONCLUSIONS: Solid-organ transplant recipients demonstrated inadequate vaccine responses (higher risk of complications and mortality) versus healthy patients. Furthermore, immune responses may differ between vaccines. Therefore, additional vaccine doses and strict control measures remain crucial.

High incidence of Candida parapsilosis candidaemia in non-neutropenic critically ill patients: epidemiology and antifungal susceptibility.

The epidemiological and antifungal susceptibility data for 35 episodes of candidemia in intensive care units (ICU) in 2007 were evaluated by prospective active surveillance. The incidence of fungaemia was 39.1 cases per 1000 ICU admissions and 2.85 cases per 1000 patient-days. The crude mortality was 65.7%; 70.8% of the fatalities occurred within 7 days of admission to the ICU. Only 2 species were isolated, Candida parapsilosis (77.1%) and Candida albicans (22.9%). There was no association between mortality and patient characteristics, prior antifungal usage, Candida subspecies or antifungal resistance (p > 0.05). Of the isolates, 5.7% were resistant to fluconazole and caspofungin, and 3.4% to voriconazole and amphotericin B. In molecular analysis of the isolates, 2 clusters of C. parapsilosis in the neurology and anaesthesiology ICUs were detected by randomly amplified polymorphic DNA (RAPD), suggesting a nosocomial transmission. In conclusion, a high incidence and high mortality rate of C. parapsilosis candidaemia were found in the ICUs. An excessive use of invasive procedures, total parenteral nutrition and broad-spectrum antibiotics in the ICUs, combined with a lack of proper infection control measures, may possibly explain the high incidence of C. parapsilosis candidaemia in our hospital.

Fungemia and cutaneous zygomycosis due to Mucor circinelloides in an intensive care unit patient: case report and review of literature.

Mucor spp. are rarely pathogenic in healthy adults, but can cause fatal infections in patients with immuosuppression and diabetes mellitus. Documented mucor fungemia is a very rare condition in the literature. We described a fungemia and cutaneous mucormycosis case due to Mucor circinelloides in an 83-year-old woman with diabetes mellitus who developed acute left frontoparietal infarctus while hospitalized in a neurological intensive care unit. The diagnosis was made based on the growth of fungi in the blood, skin biopsy cultures, and a histopathologic examination of the skin biopsy. The isolates were identified as M. circinelloides by molecular methods. This case is important in that it shows a case of cutaneous mucormycosis which developed after fungemia and provides a contribution to the literature regarding Mucor fungemia.