Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to immunocompromised populations, including lung transplant recipients. This study investigates mixed CRKP strains carrying either blaKPC-2 or blaKPC-33 following ceftazidime-avibactam (CAZ/AVI) exposure, particularly in the context of lung transplantation. Mixed CRKP strains with shifting resistance phenotypes were frequently identified in patients exposed to CAZ/AVI. We aimed to elucidate the transitional state of blaKPC variants by selecting CAZ/AVI-sensitive and -resistant CRKP strains from a lung transplantation patient.
Methods: The blaKPC-variant-carrying CRKP strains were collected from lung transplant recipients exposed to CAZ/AVI in less than two years. Antibiotic susceptibility testing (AST) was conducted using microbroth dilution, and whole-genome sequencing (WGS) was used to identify genotypes and resistance mechanisms. Limiting dilution, drop-plate, and in vitro induction experiments determined blaKPC-variant changes during CAZ/AVI administration. qPCR primers/probes were designed to identify blaKPC-2 mutations.
Results: Among 104 lung transplant recipients infected by blaKPC-harboring CRKP strains and receiving CAZ/AVI, 10 (9.6%) experienced changing resistance phenotypes. The limiting dilution method found that Patient 10's CRKP strains carried either blaKPC-2 or blaKPC-33. The drop-plate experiment showed differing growth patterns on CAZ/AVI mediums. The in vitro induction experiment demonstrated shifting from blaKPC-2 to blaKPC-33.
Conclusions: The study identified a "transitional state" of the mixed CRKP strains carrying either blaKPC-2 or blaKPC-33 in CAZ/AVI-exposed patients. Molecular diagnostics are crucial for identifying mixed strains and the transitional state of blaKPC variants, guiding treatment decisions in this complex landscape.
Background: Candida glabrata is the second most common cause of invasive candidiasis worldwide. In this study, we determined the clinical characteristics and drug sensitivity of C. glabrata isolates and investigated the associations between MSH2 gene mutations, sequence types (ST), and drug resistance.
Methods: A total of 154 C. glabrata isolates were collected from patients being treated in three hospitals in China. The antifungal sensitivity of the strains was assessed using the broth microdilution method. Multilocus sequence typing (MLST) was also performed, followed by MSH2 sequencing. The clinical features and outcomes of C. glabrata infection were analysed for a total of 49 strains, which were collected from patients with invasive Candida infection at Longhua Hospital.
Results: All 154 isolates were found to be susceptible to amphotericin, 5-fluorocytosine, anidulafungin, caspofungin, and micafungin, whereas 11.7% were fluconazole-resistant, 18.8% were itraconazole non-wild type, and 35.7% were voriconazole non-wild type. ST7 (62.34%) was the most common ST genotype, followed by ST10 (16.88%) and ST15 (7.79%). The total azole resistance rates for all isolates, ST7, ST10, and other STs were 36.4, 42.7, 34.6, and 18.8%, respectively. The ST7 and ST10 isolates were characterised by a higher drug resistance rate than the other minor ST isolates. Moreover, 59.09% of isolates had one or more MSH2 non-synonymous mutations, with V239L being the most commonly detected mutation. The frequency of MSH2 mutations was significantly higher in azole-resistant isolates than in other isolates, whereas P6L or L87P mutations were associated with the highest azole resistance rates of up to 87.5% and 80%, respectively. Our results indicated that ST7 and ST15 are independent predictors of mortality caused by C. glabrata infection and revealed a higher 30-day mortality in patients infected with these strains than in those infected with other ST isolates.
Conclusions: Our findings revealed the relationships between MLST, MSH2 gene mutations, and drug resistance in the common pathogenic fungus C. glabrata, and thereby enabled us to identify strains that are associated with higher rates of mortality. These findings will contribute to enhancing our understanding of the pathogenesis of C. glabrata infection.
Immunopathology of human tuberculosis (TB) in a subgroup of patients is characterized by aberrantly high concentrations of inflammatory cytokines, for example Interleukin (IL)-6. Concomitant (co-)infections by parasites can affect host immunity, but the impact on immunopathology in TB patients is poorly defined. Here we characterized a group of patients with TB ( n = 76) from Ghana with different protozoan and helminth co-infections. Plasma cytokines were measured at the onset of disease and anti-mycobacterial treatment efficacy was monitored during disease course. A subgroup of TB patients had co-infections with protozoan (n = 19) or helminth (n = 16) parasites. Plasma analyses for candidate cytokines identified lower levels of IL-6 in parasite co-infected patients with TB. Moreover, it took less time for co-infected patients to become sputum-negative for Mycobacterium tuberculosis during treatment. These results indicated an influence of parasite co-infections on immunopathology in TB and suggested positive effects on treatment efficacy.
Purpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging global threat, whereas its epidemiological characteristics in children are rarely reported. This study aims to analyze clinical and epidemiological characteristics of CRKP from children in Henan, China.
Methods: CRKP strains were isolated from pediatric patients, and the antimicrobial susceptibility of CRKP was determined using broth microdilution methods. The epidemiological characteristics of CRKP, including specimen sources, clinical data, carbapenemase types, virulence factors, MLST and PBRT typing were analyzed.
Results: In total, 108 CRKP isolates were isolated from specimens including sputum, blood and urine, mainly from preterm pediatric department and internal medical intensive care unit (ICU). Newborns and staying in the ICU were risk factors for crude mortality. 107 isolates exhibited a multi-drug resistant (MDR) phenotype, and one isolate was extensively drug-resistant (XDR). Bacterial susceptibility to colistin, tigecycline and trimethoprim/sulfamethoxazole was 98.10%, 78.50% and 91.43%, respectively. Carbapenemase blaKPC (86.11%) was predominant, followed by blaNDM (5.56%) and blaIMP (2.78%). Two strains co-harbored blaKPC-blaNDM, one had blaKPC-blaIMP, whereas three isolates did not carry any of the analyzed carbapenemase genes. All strains possessed fimH, and 98% of the isolates possessed mrkD. Hypervirulent factors rmpA2 and iucA showed high positive rates (71.30% and 49.07%), with 48.15% of strains containing both genes. MLST analysis identified nine distinct sequence types (STs), with ST11 (82.41%) being the most common, followed by ST2154 (4.63%) and ST307 (3.70%). PBRT analysis revealed IncFII (85.19%) as the most prevalent plasmid.
Conclusion: In summary, this study reported the epidemiological features of CRKP in pediatric patients in Henan, China, highlighting the high prevalence of multi-drug-resistant and hypervirulent strains, and underscoring the significance of continuous surveillance.
Background: Multiple studies have demonstrated the utility of sonication to improve culture yield in patients with cardiovascular implantable electronic device (CIED) infections.
Objective: To analyze the usefulness of sonication in the microbiological diagnosis of CIED infections in comparison with traditional cultures.
Methods: Systematic database searches were performed to identify studies that provided enough data concerning both sensitivity and specificity of traditional (non-sonicated) and sonicated cultures from CIED samples. The diagnostic accuracy measures were obtained by three different statistical approaches: (i) The univariate model; (ii) The bivariate random; and (iii) The Bayesian bivariate hierarchical model. Heterogeneity was assessed using meta-regression.
Findings: Nine studies met the criteria for inclusion in the meta-analysis (1684 cultures). The summary estimates of sensitivity were higher for sonicated cultures (0.756) in comparison with non-sonicated cultures (0.446). On meta-regression, sonication of CIEDs significantly increased the sensitivity (p = 0.001) as well as the rates of false positive results (p = 0.003). The final model also showed that the studies that used a threshold for positivity were associated with lower rates of false positive results (p < 0.001).
Interpretation: Our results suggest that sonication improves the microbiological diagnosis of CIED infections in comparison with traditional cultures, but a standardization of processes is necessary.
Background: It is presently considered that Corynebacterium especially Corynebacterium kroppenstedtii (CK) infection, is one of the important causes of granulomatous lobular mastitis (GLM). However, the pathogen of mastitis in the past two years has been identified as a newly discovered Corynebacterium. But it is unclear whether the pathogen associated with the occurrence of GLM is also this bacterium.
Methods: GLM female patients with positive bacterial culture in pus specimens from February 2023 to February 2024 who were identified as CK infection by mass spectrometer were selected as the research objects in this study, and the clinical isolates were identified by 16S rDNA sequencing technology to identify the specific pathogen of GLM-related bacterial infection. Subsequently, the clinical characteristics of the patients were compared with those of GLM patients without bacterial infection during the same period, to explore the effect of this particular type of Corynebacterium infection on disease development in GLM patients. Finally, we tested the minimum inhibitory concentration (MIC) values of antibiotics when inhibiting these separation strains in vitro through the E-Test experiment, to evaluate their medicine sensitivity.
Results: A total of 31 GLM patients initially diagnosed with Corynebacterium kroppenstedtii (CK) infection via MALDI-TOF MS were enrolled in the study. However, subsequent 16S rDNA sequencing revealed that 28 isolates (90.32%) were actually identified as the newly recognized Corynebacterium parakroppenstedtii (CPK). This discovery challenges the conventional belief that CK is the primary pathogen of GLM, suggesting instead that CPK is the predominant pathogen associated with GLM bacterial infections. Comparative analysis of the clinical characteristics between the two groups revealed a significantly higher recurrence rate among CPK-infected GLM patients compared to those without CPK infection, along with elevated prolactin levels (P < 0.05). The sensitivity test results indicated high sensitivity of the isolates to vancomycin, linezolid, and rifampicin.
Conclusion: In conclusion, this study highlights that Corynebacterium kroppenstedtii strains isolated from GLM specimens were Corynebacterium parakroppenstedtii, serving as the primary pathogen closely linked to GLM's occurrence. CPK infection significantly increases the risk of recurrence in GLM patients, with elevated prolactin levels potentially playing a pivotal role in this process. In clinical antimicrobial treatment, antimicrobials other than penicillin and ciprofloxacin may be empirically administered when sensitivity test results are inconclusive.
Objective: This study aims to present a case of persistent mycetoma caused by Scedosporium boydii and undertake a systematic literature overview to elucidate the clinical characteristics and antifungal treatment exhibited by such patients.
Methods: We report the case of a 24-year-old female who sustained a Scedosporium boydii infection in her right foot over a decade ago following a nail puncture. Concurrently, a comprehensive literature overview was conducted on PubMed, focusing on documented cases of Scedosporium boydii infections with the intent of extracting relevant clinical data.
Results: Our analysis revealed that post-transplantation, trauma, near drowning, corticosteroid administration, and prior surgical history were the main risk factors for Scedosporium boydii infection. Prevalent infection sites included skin/bone tissues, the central nervous system, and ocular regions. Among the 49 patients identified, 24 received itraconazole therapy and 25 received voriconazole, with no significant difference in patient outcomes (P = 0.158). Of these, 12 patients experienced treatment failure. Notably, prolonged antifungal treatment duration was identified as a protective factor against mortality in Scedosporium boydii infections [P = 0.022, OR(95%CI): 0.972(0.949-0.996)]. Conversely, a history of post-transplantation emerged as a potential risk factor for mortality[P = 0.046, OR(95%CI): 7.017(1.034-47.636)].
Conclusion: While uncommon, Scedosporium boydii infections carry a significant burden of morbidity and adverse outcomes. Heightened clinical vigilance is warranted in individuals presenting with risk factors for this pathogen. Timely and effective antifungal intervention is crucial, with both voriconazole and itraconazole demonstrating positive treatment outcomes for Scedosporium boydii infection. Therefore, prioritizing these antifungal agents should be considered a key therapeutic strategy in the management of this patient population.
Background: Determination of SARS-CoV-2 variant is significant to prevent the spreads of COVID-19 disease.
Methods: We aimed to evaluate the variants of SARS-CoV-2 rate in positive patients in Kanuni Sultan Suleyman Training and Research Hospital (KSS-TRH), Istanbul, Türkiye between 1st January and 30th November 2021 by using RT-PCR method.
Results: Herein, 825,169 patients were evaluated (male:58.53% and female:41.47%) whether COVID-19 positive or not [( +):21.3% and (-):78.7%] and 175,367 patient was described as positive (53.2%-female and 46.8%-male) by RT-PCR. COVID-19 positive rate is observed highest in the 6-15- and 66-75-year age range. The frequencies were obtained as SARS-CoV-2 positive (without mutation of B.1.1.7 [B.1.1.7 (U.K), E484K, L452R, B.1.351 (S. Africa/Brazil) spike mutations] as 66.1% (n: 115,899), B.1.1.7 Variant as 23.2% (n:40,686), Delta mutation (L452R) variant as 9.8% (n:17,182), B.1.351 variant as 0.8% (n:1370) and E484K as 0.1% (n: 230). In April 2021, general SARS-CoV-2 and B.1.1.7 variant were dominantly observed. Up to July 2021, B.1.617.2 (Delta variant/ Indian variant) and E484K has been not observed. B.1.351 variant of SARS-CoV-2 has been started in February 2021 at the rarest ratio and March 2021 is the top point. September 2021 is the pick point of E484K. African/Brazil variant of SARS-CoV-2 has been started in February 2021 at the rarest ratio and March 2021 is the top point. September 2021 is the pick point of E484K. When the gender type is compared within the variants, women were found to be more prevalent in all varieties.
Conclusions: The meaning of these mutations is very important to understand the transmission capacity of the COVID-19 disease, pandemic episode, and diagnosis of the virus with mutation types. Understanding the variant type is important for monitoring herd immunity and the spread of the disease.
Introduction: Gram-negative bacteremia is a life-threatening infection with high morbidity and mortality. Its incidence is rising worldwide, and treatment has become more challenging due to emerging bacterial resistance. Little data is available on the burden and outcome of such infections in Lebanon.
Methods: We conducted this retrospective study in four Lebanese hospitals. Data on medical conditions and demographics of 2400 patients diagnosed with a bloodstream infection based on a positive blood culture were collected between January 2014 and December 2020.
Results: Most bacteremias were caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, with the more resistant organisms being hospital-acquired. Third-generation cephalosporin and quinolone resistance was steady throughout the study, but carbapenem resistance increased. Mortality with such infections is high, but carbapenem resistance or infection with Pseudomonas or Acinetobacter species were significant risk factors for poor outcomes.
Conclusion: This is the first multi-center study from Lebanon on gram-negative bacteremia, resistance patterns, and factors associated with a poor outcome. More surveillance is needed to provide data to guide empirical treatment for bacteremia in Lebanon.
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