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.

Antimicrobial dosing recommendations during continuous renal replacement therapy: different databases, different doses.

Meticulous antimicrobial management is essential among critically ill patients with acute kidney injury, particularly if renal replacement therapy is needed. Many factors affect drug removal in patients undergoing continuous renal replacement therapy CRRT. In this study, we aimed to compare current databases that are frequently used to adjust CRRT dosages of antimicrobial drugs with the gold standard. The dosage recommendations from various databases for antimicrobial drugs eliminated by CRRT were investigated. The book 'Renal Pharmacotherapy: Dosage Adjustment of Medications Eliminated by the Kidneys' was chosen as the gold standard. There were variations in the databases. Micromedex, UpToDate, and Sanford had similar rates to the gold standard of 45%, 35%, and 30%, respectively. The Micromedex database shows the most similar results to the gold standard source. In addition, a consensus was reached as a result of the expert panel meetings established to discuss the different antimicrobial dose recommendations of the databases.

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.

Evaluation of Clinical Approach and Outcomes Staphylococcus aureus Bacteremia.

Objective: Despite appropriate treatment and early diagnosis methods, Staphylococcus aureus bacteremia (SAB) is still associated with a high mortality rate. This study aims to evaluate the clinical features and approaches to SAB and to analyze the parameters that may affect 7-day and 30-day mortality. Materials and Methods: Adult patients with SAB data between 2011 and 2018 were evaluated retrospectively. Clinical data, patient demographics, and 7-day and 30-day mortality rates were obtained from their medical records. Results: In total, 144 patients were included in the study; 57.6% (83/144) of patients were men, and the mean age was 65.2±16.5 years. The most common source of infection was the central-line catheter (38.9%), followed by intra-abdominal (21%), respiratory (16.7), infective endocarditis (5.6%), and osteoarticular foci (2.1%). Fifteen percent (15%) of the strains were methicillin resistant. Transthoracic echocardiography (TTE) was performed for 80.6% (116/144) patients. Infectious diseases specialist consultation within 96 hours from blood culture signal was requested in 79.9%. Overall, 7-day mortality was 11.8%, and 30-day mortality was 21.5%. Staying in intensive care units (ICU) increased the risk of 30-day mortality by 1.1 times, and respiratory-focused SAB increased the risk by 4.3 times. Conclusion: SAB is still a big threat. Staphylococcal pneumonia remains a severe infection. Several prognostic factors influence mortality. Identifying the source, ensuring source control, and appropriate initial therapy as soon as possible are critical for reducing mortality and morbidity in SAB.

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.

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.

Evaluation of extensively drug-resistant gram-negative bacteremia among solid-organ transplant recipients: a multicenter study

Background/aim: The aim of this study is to evaluate the distribution, sources, clinical features, and mortality rates of bacteremia due to evaluation of extensively drug-resistant (XDR) gram negative among solid-organ transplant (SOT) recipients. Materials and methods: A retrospective study of SOT recipients with bacteremia due to XDR gram-negative pathogens in 11 centers between 2016 and 2018 was conducted. Patients' records were evaluated. Results: Of 171 bacteremia that occurred in 164 SOT recipients, 93 (56.7%) were liver, 46 (28%) kidney, 14 (8.5%) heart, and 11 (6.7%) lung recipients. Bacteremia episodes were recorded in the first year in 63.7% of the patients (n = 109), early-onset bacteremia was recorded in 45% (n = 77) of the episodes. In multivariate analysis, catheter-associated bacteremia was an independent risk factor for 7-day mortality (p = 0.037), and early-onset bacteremia was found as an independent risk factor for 30-day mortality (p = 0.017). Conclusion: Difficult-to-treat infections due to XDR bacteria in SOT recipients shadow the success of transplantation. Central venous catheters seem to be the main risk factor. Judicious use of medical devices is of pivotal importance.