Melike Yaşar Duman

Background: Carbapenem-resistant Enterobacterales (CRE) are a major therapeutic challenge, particularly in settings where metallo-β-lactamases are prevalent. Aztreonam–avibactam (AZA) may provide activity against metallo-β-lactamase-producing isolates, whereas ceftazidime–avibactam (CZA) has limited activity against the isolates that harbor these enzymes. This study aimed to evaluate the in vitro activity of aztreonam–avibactam and ceftazidime–avibactam against invasive carbapenem-resistant Enterobacterales isolates and to characterize the distribution of carbapenemase genes in a tertiary-care center in Türkiye. Methods: A total of 100 non-duplicate CRE isolates recovered from blood cultures and sterile body fluids between January 2024 and January 2026 were included. Species identification and routine antimicrobial susceptibility testing were performed using MALDI-TOF MS and an automated system. CZA and AZA MICs were determined by gradient diffusion testing, whereas CZA–aztreonam synergy was assessed separately using a disk/gradient diffusion-based method. Carbapenemase genes were detected by real-time PCR. Whole-genome sequencing was performed for the two AZA-resistant Escherichia coli isolates. Results: The isolate collection was dominated by Klebsiella pneumoniae (87.0%), and most isolates were recovered from blood cultures (80.0%). CZA susceptibility was observed in 31.0% of isolates, with MIC_50/90 values of 256/256 mg/L. In contrast, AZA showed high in vitro activity, with 98.0% of isolates categorized as susceptible and MIC_50/90 values of 0.25/0.50 mg/L. CZA–aztreonam synergy was detected in 98.0% of isolates. Qualitative CZA–aztreonam synergy testing did not fully concord with direct AZA MIC-based susceptibility categorization: one AZA-resistant isolate showed a positive synergy result, whereas one synergy-negative isolate remained AZA-susceptible. Carbapenemase genes were detected in 99.0% of isolates; bla_NDM was the most frequent gene (81.0%), followed by bla_OXA-48 (72.0%), bla_KPC (14.0%), and bla_VIM (4.0%). The most common carbapenemase profile was bla_NDM + bla_OXA-48 (62.0%). bla_NDM carriage was strongly associated with CZA resistance, and CZA MICs were significantly higher among bla_NDM-positive isolates. The two AZA-resistant E. coli isolates belonged to ST500 and ST410, and both carried a YRIK insertion in PBP3; one of them additionally showed ompF disruption associated with a 4 bp insertion. Conclusions: AZA demonstrated potent in vitro activity against invasive CRE isolates in this setting, whereas CZA activity was substantially limited, likely reflecting the high prevalence of bla_NDM and frequent carbapenemase co-carriage. These findings support the potential value of AZA in regions with emerging metallo-β-lactamase predominance and highlight the importance of local molecular surveillance to guide antimicrobial strategies.

Pediatric candidemia is a major cause of invasive fungal infections in hospitalized children, but long-term data on epidemiology, management, and mortality predictors remain limited. We conducted an 18-year retrospective cohort study of 465 pediatric candidemia episodes at a tertiary referral center in western Turkey between 2008 and 2025. The primary outcome was crude 30-day mortality; associated factors were assessed using univariable analyses, Kaplan–Meier estimates, and multivariable logistic regression. Non-albicans Candida species predominated, with Candida parapsilosis as the most frequent isolate (46%). Central venous catheters were present in 88.4% of episodes. Crude 30-day mortality was 10.8%. Reduced survival was observed among patients without catheter removal and among those with thrombocytopenia, severe neutropenia, or immunosuppressive therapy. Among 341 episodes classified as central line-associated bloodstream infections, crude 30-day mortality differed significantly by catheter removal timing. Mortality was 4.8% with catheter removal within 72 h versus 13.1% without early removal (p = 0.022). Using a 48 h threshold, mortality was 3.1% with removal within 48 h versus 12.3% without removal within 48 h (p = 0.029). In multivariable analysis, failure to remove the catheter was the strongest independent factor associated with mortality (adjusted odds ratio, 6.63; 95% confidence interval, 2.85–15.42; p < 0.001). Antifungal resistance patterns were not consistently associated with mortality. In this large pediatric candidemia cohort, 30-day mortality was mainly associated with host vulnerability and modifiable management factors, underscoring the importance of timely source control.

Background: Mucormycosis is a life-threatening angioinvasive fungal infection that primarily affects immunocompromised individuals, especially those with diabetes mellitus or hematologic malignancies. Despite its clinical importance, a comprehensive synthesis of mucormycosis cases from Türkiye is lacking. This study aimed to review and synthesize the published case reports on mucormycosis in Türkiye systematically. Materials and Methods: Mucormycosis case reports from Türkiye published between 1 January 1966 and 30 November 2024 were reviewed and analyzed, with an emphasis on demographics, clinical characteristics, treatment strategies, and outcomes. Results: A total of 199 cases from 155 publications were included. Mean age was 47.7 years, and 51.8% of patients were male. Diabetes mellitus was the most frequent underlying condition (65.8%), followed by hematologic malignancies (16.6%). Rhino-cerebral involvement was the predominant clinical form (86.4%). Histopathological confirmation was reported in 91.0% of cases, whereas microbiological confirmation was available in 47.7%. Overall mortality was 43.7%. Surgical debridement was performed in 69.3% of cases, and crude mortality was lower among patients who underwent surgery than among those who did not. Liposomal amphotericin B was the most frequently reported antifungal agent. Conclusions: This study provides a national descriptive synthesis of published mucormycosis cases from Türkiye over nearly six decades. The findings highlight the predominance of diabetes-associated rhino-cerebral disease, frequent reliance on histopathology, and the importance of combined medical–surgical management in routine practice. Because the dataset is based on heterogeneous published case reports and case series spanning a long time period, treatment-outcome findings should be interpreted descriptively.

Antimicrobial resistance (AMR) among Gram-negative (GN) pathogens has emerged as a critical global threat, particularly in low- and middle-income countries where access to novel antimicrobials is limited. In Türkiye, colistin (CST) remains a last-resort therapy against multidrug-resistant (MDR) and carbapenem-resistant Gram-negative bacteria (CR-GNB) despite its nephrotoxic potential. This study aimed to evaluate the clinical characteristics, microbiological outcomes, and adverse events associated with CST therapy in pediatric patients over a nine-year period. We conducted a single-center retrospective cohort study including pediatric patients treated with CST for nosocomial MDR-GN infections at a tertiary university hospital between January 2016 and March 2025. Demographic, clinical, microbiological, and treatment-related data were collected. Univariable comparisons and multivariable logistic regression analyses were performed to identify factors associated with nephrotoxicity, treatment failure, and mortality. A total of 117 treatment episodes were identified among 112 patients (mean age: 75.9 ± 69.5 months; 65% male). The predominant pathogens were Klebsiella pneumoniae (39.7%), Pseudomonas aeruginosa (26.4%), and Acinetobacter baumannii (22.0%). CST was used in combination regimens in all episodes, most commonly with carbapenems (73.5%). Microbiological eradication was achieved in 70% of culture-confirmed episodes. The overall sepsis-related mortality rate was 18.8%. Nephrotoxicity occurred in 12.8% of patients and was associated with mortality and severity indicators in univariable analyses. In multivariable analysis, endotracheal intubation remained the only independent predictor of mortality (adjusted OR 23.98, 95% CI 4.47–128.52). Conclusions : CST remains a last-resort agent for MDR and CR-GNB infections in pediatric settings with limited access to novel antimicrobials. Although microbiological eradication was achieved in most cases, treatment outcomes were primarily driven by disease severity and host-related factors rather than antimicrobial combinations. Endotracheal intubation emerged as the strongest independent predictor of mortality. What is Known – What is New • CST is widely used as a last-resort option for pediatric MDR-GN infections. • Nephrotoxicity and variable clinical outcomes remain major concerns. • This study provides long-term real-world pediatric data on CST use. • Disease severity and host-related factors were the main determinants of treatment failure and mortality.

Introduction: The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) limits effective treatment options. The aim of this study was to evaluate the susceptibility patterns of CR-Kp strains isolated from urine cultures to oral treatment options recommended by the Infectious Diseases Society of America guidelines, and ceftazidime-avibactam. Additionally, clinical data and outcomes of patients diagnosed with CR-Kp urinary tract infections (UTI) who were treated with fosfomycin sodium-including therapy regimens (FSITR) were analyzed. Methodology: This retrospective cohort study included adult patients with urine culture-proven CR-Kp between March 2016 and October 2022. Demographic and clinical data, antibiotic susceptibility, treatment outcomes, and one-month mortality (OMM) were evaluated. Results: A total of 179 patients were included. The susceptibility to fosfomycin tromethamol, nitrofurantoin, and co-trimoxazole (TMP-SMX) were (33.7%; 55/163), (7.7%; 13/167), and (11.1%; 20/179), respectively. All strains were resistant to ciprofloxacin. The susceptibility data compared until 2020 (pre-COVID-19) and afterwards, revealed TMP-SMX susceptibility (4.9% vs 24.1%, p = 0.0001) increased significantly. Susceptibility data for ceftazidime-avibactam were available for 22 isolates and 59% of the isolates were sensitive. OMM of the 179 patients with CR-Kp in urine cultures was 37.4% (67/179). There were 9 FSITR cases. Among those, microbiological eradication was achieved in 87.5% (7/8) and OMM was 44.4% (4/9). Conclusions: Clinical experience may be feasible and needed to assess the efficacy of nitrofurantoin and TMP-SMX. Fosfomycin-including regimens may serve as a salvage treatment option for CR-Kp UTI in selected patients. However, the retrospective and single-center design of the study should be considered as a limitation.

Bu çalışmada, çölyak hastalığı (ÇH)'nın tanısında kullanılan anti-endomisyum (EMA) IgA antikorlarının saptanmasında maymun özofagus (MÖ) ve maymun karaciğer (MK) preparatlarının tanısal performanslarının karşılaştırılması ve anti-doku transglutaminaz (anti-TTG) IgA ile anti-deamin gliyadin peptit (GAF3X) IgA düzeyleriyle ilişkisinin değerlendirilmesi amaçlanmıştır. Metodolojik ve kesitsel tasarımlı bu çalışmaya, selektif IgA eksikliği olmayan, ÇH ön tanılı 123 hasta dahil edilmiştir. EMA IgA testleri, MÖ ve MK preparatları kullanılarak indirekt immün floresan mikroskopisi (IIF) yöntemiyle değerlendirilmiştir. Serolojik testler (anti-TTG IgA ve GAF3X IgA) ELISA yöntemiyle analiz edilmiş, bağırsak biyopsisi sonuçları Marsh sınıflamasına göre kategorize edilmiştir. Testlerin tanısal performansı; duyarlılık, özgüllük, pozitif ve negatif prediktif değerler kullanılarak değerlendirilmiştir. Gruplar arasındaki farklar istatistiksel analizlerle incelenmiştir. Anti-TTG IgA pozitifliği saptanan 90 vakanın %96.67'si MK, %88.89'u ise MÖ testlerinde pozitif olarak değerlendirilmiştir. MÖ ve MK testleri arasında yüksek düzeyde bir uyum bulunmuş (Kappa= 0.692, p< 0.001), her iki preparatın da EMA IgA pozitifliğini saptamada benzer etkinliğe sahip olduğu gösterilmiştir. Ayrıca, Marsh skoru pozitifliği ile serolojik test sonuçları arasında güçlü bir ilişki saptanmıştır. MK testinin duyarlılığı %100, özgüllüğü %50, pozitif prediktif değeri %86 ve negatif prediktif değeri %100 olarak hesaplanmıştır. MÖ testi için ise duyarlılık %97.7, özgüllük %64.3, pozitif prediktif değeri %89.4 ve negatif prediktif değeri %90 bulunmuştur. Çocuk ve yetişkin grupları arasında kantitatif test sonuçlarında anlamlı farklılıklar gözlenmiştir (MK: p= 0.006; MÖ: p= 0.048). Ancak Marsh skoru pozitifliği üzerinde yaşın (p= 0.268) ve cinsiyetin (p= 0.775) etkisi istatistiksel olarak anlamlı bulunmamıştır. "Correspondence" analizi, MÖ ve MK kategorileri arasında istatistiksel olarak anlamlı bir ilişki göstermiştir (p< 0.001) ve pozitif kategorilerde yüksek düzeyde bir korelasyon tespit edilmiştir. Anti-TTG IgA testi için yapılan alıcı işletim karakteristiği analizi sonucunda eğri altındaki alan değeri 0.822 olarak hesaplanmış, bu değer testin Marsh skoru pozitifliği ile negatifliğini ayırt etme kapasitesinin oldukça iyi olduğunu ortaya koymuştur. Optimal kesme noktası olarak belirlenen 223.84 RU/mL'de testin duyarlılığı %60.5, özgüllüğü ise %100 olarak bulunmuş, bu değer yüksek özgüllük ve biyopsi gerekliliğini azaltma potansiyeli açısından önem arz etmiştir. Sonuçlar, EMA IgA ve diğer serolojik testlerin ÇH tanısında yüksek tanısal değer sunduğunu desteklemiştir. EMA IgA testlerinin MÖ ve MK preparatları ile kullanımı, ÇH tanısında etkili bir serolojik yöntem olarak değerlendirilmiştir. MK preparatları, MÖ preparatlarına kıyasla daha yüksek duyarlılık sergilemiş ancak özgüllük açısından sınırlı bulunmuştur. Anti-TTG IgA testinin Marsh skoru pozitifliği ile ilişkisinde belirlenen optimal kesme noktası, klinik karar süreçlerine katkı sağlayabilir. Bu bulgular, biyopsi gerekliliğini azaltmayı hedefleyen tanısal yaklaşımlara ışık tutmuştur.

Objective: This study aims to analyze the clinical and microbiologic characteristics of febrile episodes in pediatric oncology patients undergoing chemotherapy, with and without neutropenia. Patients and Methods: A retrospective analysis was conducted on 212 febrile episodes in 94 pediatric cancer patients hospitalized between January 2015 and December 2018. Patients with fever ≥38°C were included. Data were extracted from electronic health records. Infection diagnoses were established based on clinical examination and microbiologic studies. Results: Among the 212 febrile episodes, 117 (55.1%) were classified as febrile neutropenia. Infection foci were identified in 51.4% of cases, with catheter infections being the most common (18.4%), followed by viral upper respiratory tract infections (16%). Microbiologic analysis identified bacterial agents in 69 cases. The most frequently identified bacteria were Coagulase-negative Staphylococcus and Escherichia coli. Septic shock occurred in 7 febrile episodes (3.3%), all in neutropenic patients. There was no statistically significant difference in infection rates between neutropenic and non-neutropenic groups (P>0.05), except for septic shock, which was significantly higher in neutropenic patients (P=0.02). Conclusions: Our data suggest that infections remain a major cause of morbidity in pediatric oncology patients regardless of neutropenic status. We believe that prospective and multicenter studies are also necessary to optimize infection management strategies in non-neutropenic patients with fever as well as neutropenic ones.