Infection and Drug Resistance最新文献

Introduction: This study assessed the clinical burden of carbapenemase-producing Enterobacterales (CPE) infections according to different resistance mechanisms among Enterobacterales isolates in Spain.

Methods: This retrospective study was conducted in five Spanish hospitals from the National Mapping of Carbapenemases in Spain study. Patients were included if they were 18 years or older; had a diagnosis of complicated intraabdominal infection (cIAI), complicated urinary tract infection (cUTI), bloodstream infection (BSI), or hospital-acquired or ventilator-acquired bacterial pneumonia (HABP/VABP) between 2017 and 2018; and had a confirmed CPE isolate.

Results: In total, 118 patients were evaluable for clinical outcomes. The most common mechanism of carbapenem resistance was Klebsiella pneumoniae carbapenemase (KPC; n = 82, 69.5%), followed by OXA-48 (n = 27, 22.9%) and metallo-β-lactamases (MBL; n = 9, 7.6%). Overall, 75 patients (63.6%) died from any cause, including 21 deaths (28.0% of all deaths) attributable to the current infection. Clinical cure was achieved in 92 patients (78.0%) and microbiological cure in 59 (54.6%). Among the 92 patients discharged alive, 29 (31.5%) were readmitted for an infectious disease, and relapse within 30 days occurred in 10 patients (10.9%).

Discussion: Data suggest that CPE infections are associated with a high disease burden, low rates of clinical cure, and high rates of relapse and mortality in Spain. However, results should be interpreted with caution due to the limited sample size which may have restricted the precision of these estimates and gaps in minimal inhibitory concentration data availability.

Background: Invasive fungal infections were rare but serious complication in pediatric patients following cardiac surgery. Data on the epidemiology, clinical characteristics, and preventive strategies remain limited.

Methods: This was a retrospective before-after study. We reviewed a prospectively maintained database in our pediatric cardiac ICU between 2018 and 2024. All patients who developed invasive fungal infections following cardiac surgery were included. Since our center began the invasive fungal infections prevention bundle in 2021, patients from 2018 to 2020 were included in pre-bundle group, patients from 2021 to 2024 were included in post-bundle group. Our fungal prevention bundle included: 1) Actively providing prophylactic antifungal drugs based on risk stratification. 2) Enhancing hospital acquired infection management. 3) Multi-disciplinary treatment, clinical pharmacists participate in antimicrobial stewardship. 4) Establishing an ICU infection control team to ensure the implementation of the above measures.

Results: In this cohort of 19,761 postoperative pediatric patients, 38 cases (0.19%) of invasive fungal infections were identified, all manifesting as fungal sepsis. Clinical manifestations of infection included fever, an increased leukocyte count, neutrophil percentage, (1,3)-β-D-glucan, C-reactive protein and procalcitonin value. Fourteen patients (37%) exhibited circulatory instability. The median time from surgery to infection was 23 (8, 56) days, with a mortality rate of 24%. Comparative analysis between study periods revealed improvements in infection control measures. Hand hygiene compliance increased from 48% to 61% (P < 0.001), antibiotic consumption (defined daily dose) reduced from 32.7 to 27.5 (P < 0.001). Following group stratification, the incidence of invasive fungal infections was lower in post-bundle group (0.11%; 12/11,194) than in pre-bundle group (0.3%; 26/8567), P = 0.002.

Conclusion: Based on the study findings, the implementation of a multifaceted fungal prevention bundle was associated with a significant reduction in the incidence of invasive fungal infections in pediatric patients after cardiac surgery.

Background: Talaromyces marneffei (TM), an opportunistic fungal pathogen, causes severe infections in immunocompromised individuals. While endemic to tropical regions of Southeast Asia and South Asia, sporadic cases have been reported in non-endemic areas. Diagnosis is often delayed due to nonspecific clinical and laboratory features, contributing to high mortality.

Case presentation: A HIV-positive patient subsequently developed TM pulmonary infection. Clinical symptoms and laboratory test results were non-specific. Imaging studies revealed pulmonary masses, and the patient was misdiagnosed with lung cancer outside the hospital, leading to an erroneous surgical resection. The patient did not improve postoperatively but instead developed high fever and persistent cough, with symptoms worsening. During treatment at our hospital, the patient was definitively diagnosed with TM lung infection, not lung cancer. Due to the rarity of TM infection and lack of experience, treatment was delayed, leading to worsening of the patient's condition. The patient exhibited gastrointestinal bleeding, progressive neurological dysfunction, hydrocephalus, and multi-organ dysfunction, which ultimately resulted in the death of the patient.

Conclusion: TM infections often present with insidious onset, prolonged course, and lack of specific clinical symptoms, imaging findings, or laboratory test characteristics, making diagnosis challenging and frequently leading to misdiagnosis or missed diagnosis, resulting in high mortality rates. Therefore, clinicians should enhance their diagnostic and treatment experience regarding TM infections in HIV-positive individuals or populations in non-endemic regions, initiate pathogen culture and histopathological diagnosis as early as possible, and integrate the results of mNGS and mass spectrometry analysis to improve the detection rate and early diagnosis rate of TM infections. This will ensure that patients can receive timely and accurate treatment, which is crucial for improving their prognosis.

Purpose: Pneumocystis jirovecii typically causes life-threatening Pneumocystis pneumonia (PCP), calling for accurate detection of P. jirovecii in clinical samples to facilitate PCP management.

Patients and methods: An observational cohort of 193 patients with suspected fungal pneumonia was enrolled. The cell-free DNA (cfDNA) in bronchoalveolar lavage fluid (BALF) and serum samples was prepared and quantitated via a ddPCR assay targeting the mitochondrial large subunit rRNA gene of P. jirovecii. The correlations between ddPCR results and medical data were analyzed.

Results: The cases with complete data were classified into a PCP group (N=30) and a non-PCP group (N=139). This ddPCR assay demonstrated a sensitivity of 91.3% and a specificity of 96.8% for BALF, in contrast to a sensitivity of 57.1% and a specificity of 100% for serum. The area under the curve of 0.896 for diagnosis was obtained via ddPCR assay, compared with 0.627 via G-test (P<0.0001). The cfDNA copies were positively correlated with antifungal agents usage, certain clinical characteristics, lactate dehydrogenase levels, and G-test results (all P<0.05). Moreover, higher cfDNA copies were associated with increased in-hospital mortality (aHR>1, P<0.05).

Conclusion: The ddPCR assay exhibited robust diagnostic performance for PCP in BALF samples and cfDNA copies may serve as an indicator for improving the management of patients.

Introduction: Nontuberculous mycobacteria such as Mycobacterium kansasii can mimic malignancy on imaging and pathology, leading to prolonged diagnostic uncertainty and inappropriate anticancer therapy.

Case report: A 76-year-old woman with remote right breast carcinoma (mastectomy and adjuvant therapy in 1996) had a persistent right chest-wall lesion with rib changes and encapsulated pleural effusion repeatedly interpreted as metastatic disease from 2017 to 2023, despite multiple biopsies showing only fibrous hyperplasia. In August 2024, fever and cough prompted re-evaluation. PET-CT demonstrated a hypermetabolic pleura-adjacent lesion (SUVmax 10.8) without distant metastases. Plasma metagenomic next-generation sequencing (mNGS) yielded a low-level M. kansasii signal; pleural fluid mNGS identified 146 reads (94% relative abundance), later confirmed by culture. Targeted anti-NTM therapy stabilized the infection; however, the patient developed severe varicella-zoster virus infection and cardiac complications and subsequently died. The death was attributed to these complications rather than the progression of the M. kansasii infection.

Conclusion: Chronic M. kansasii pleural infection can masquerade as metastatic breast cancer for years. PET-CT alone is insufficient to distinguish infection from malignancy; careful imaging review combined with unbiased mNGS can establish the diagnosis and avert unnecessary anticancer therapy. Multidisciplinary collaboration is essential for timely recognition and management.

Background: Vibrio vulnificus is a halophilic marine bacterium capable of causing rapidly progressive septic shock and necrotizing fasciitis, particularly in immunocompromised individuals. Mortality rates remain high due to the fulminant nature of the infection and diagnostic challenges.

Case presentation: A 70-year-old female with poorly controlled type 2 diabetes presented with fever and septic shock 48 hours after ingesting raw seafood. The clinical course was characterized by rapid deterioration, severe coagulopathy, and the development of extensive necrotizing fasciitis in the right upper limb. Vibrio vulnificus infection was confirmed via next-generation sequencing (NGS) on hospital day 6. Despite broad-spectrum antibiotic therapy and fluid resuscitation, surgical intervention was delayed until day 9 following multidisciplinary consultation. Intraoperative findings revealed extensive "dishwater" necrosis. The patient suffered from recurrent sepsis, graft failure, and deep vein thrombosis. Due to the rapid progression and delayed source control, the outcome was unfavorable, leading to discharge against medical advice.

Conclusion: This case underscores the high mortality risk associated with Vibrio vulnificus infection in immunocompromised individuals, particularly those with diabetes mellitus. Observations from this patient highlight that antibiotic therapy alone is often insufficient for necrotizing soft tissue infections. It is emphasized that in these high-risk populations, early recognition must trigger immediate, aggressive surgical debridement alongside antimicrobial therapy. Delays in surgical source control, even while awaiting molecular confirmation, can irreversibly compromise patient survival.

Polymyxins are critical for multidrug-resistant Gram-negative infections, yet severe neurotoxicity remains underrecognized, within Guillain-Barré Syndrome (GBS) has not been previously reported in association with polymyxin E. We report two cases illustrating a temporal association between polymyxin therapy and severe neurological manifestations. The first is a case of polymyxin B-induced respiratory paralysis in a patient with bloodstream infection. The second represents the first reported case of GBS associated with polymyxin E (Colistin Methanesulfonate) in a patient with pneumonia; the diagnosis was confirmed electrophysiologically, and the patient responded to immunotherapy. These findings suggest a potential link between polymyxin therapy and severe, atypical neurotoxicity. Clinicians should be vigilant for symptoms ranging from acute paresthesia to GBS, as early recognition and drug discontinuation are crucial to preventing severe outcomes.

Purpose: Isoniazid (INH), a first-line anti-tuberculosis agent, exhibits variable cerebrospinal fluid (CSF) penetration owing to NAT2 genetic polymorphisms. This study developed an LC-MS/MS method to quantify INH in the human CSF for therapeutic drug monitoring in patients with tuberculous meningitis.

Methods: The LC-MS/MS method developed and validated in this study includes linearity, sensitivity, accuracy, precision, extraction recovery, matrix effect, and stability evaluations, all of which meet the standards for bioanalytical method validation. This method was applied to a real-world prospective observational study to compare CSF trough concentrations of INH between patients receiving conventional anti-tuberculosis therapy and those receiving conventional therapy combined with intrathecal INH injection, and a pharmacokinetic study was conducted in one TBM patient.

Results: The validated LC‑MS/MS method achieved a total run time of 3.5 min, demonstrated linearity over the range of 5-4000 ng/mL, and had an LLOQ of 5 ng/mL, with all validation parameters meeting acceptance criteria. In the clinical cohort, the median CSF trough concentration of INH was significantly higher in the intrathecal therapy group (1130.00 ng/mL, N=117) than in the conventional therapy group (155.00 ng/mL, N=45, P<0.001). Target attainment rates at ≥120 ng/mL and ≥250 ng/mL were also significantly greater in the intrathecal group (84.62% and 77.78%, respectively) versus the conventional group (57.78% and 35.56%, both P<0.001). Pharmacokinetic analysis in a TBM patient after intrathecal INH administration revealed a T_mₐₓ of 6 h, C_mₐₓ of 2810 ng/mL, and an elimination half‑life of approximately 14 h.

Conclusion: A sensitive and reliable LC-MS/MS method was successfully developed and validated for quantification of INH in human CSF. This study confirms that intrathecal administration of INH can significantly increase drug concentrations in the CSF of TBM patients, providing methodological support and preliminary clinical evidence for optimizing treatment strategies in TBM.

Purpose: Pneumonia is still a leading cause of morbidity and death globally, with a significant percentage of cases having an unknown aetiology, and management becoming more difficult due to growing antimicrobial resistance (AMR). This study assessed clinical outcomes, antimicrobial susceptibility patterns, and pathogen detection using both conventional and molecular techniques in hospitalized pneumonia patients in Jordan.

Patients and methods: 111 adults (≥18 years) who were admitted to a tertiary private hospital in Amman between May 2021 and January 2022 with either hospital-acquired (HAP) or community-acquired pneumonia (CAP) were included in this prospective study. Multiplex real-time PCR and conventional culture were performed on lower respiratory tract samples (FTD Respiratory Pathogens 33). Data on outcomes, microbiology, antimicrobial susceptibility, clinical, and demographics were gathered. McNemar's test was used to compare diagnostic performance, and logistic regression and chi-square analyses were used to evaluate the relationships between outcomes and adherence to guidelines.

Results: The average age was 64.0±20.6 years, and 58.6% of the population was male. 78.4% of cases were CAP. PCR detected pathogens in 74.8% of patients, whereas culture detected them in 57.7% (p<0.001). PCR showed a higher false-positive rate but a significantly higher sensitivity than culture (96.9% vs 86.3%, p=0.039). In 36.9% of cases, bacterial-viral co-infections were found. The overall death rate was 27.0%. Although not an independent predictor in logistic regression, non-guideline-concordant antibiotic therapy was substantially associated with mortality (p=0.023). High ampicillin resistance and notable trends in resistance to specific broad-spectrum agents were among the notable variations in AMR patterns observed.

Conclusion: Multiplex PCR reveals complex co-infection patterns in pneumonia and greatly enhances pathogen detection when compared to culture. Antimicrobial stewardship initiatives that incorporate molecular diagnostics may improve targeted treatment. To address changing AMR patterns in Jordan, national guidelines that include molecular testing are necessary.

Antimicrobial resistance (AMR) is a critical global public health threat, particularly in fragile and conflict-affected settings. In Somalia, decades of armed conflict, large-scale displacement, and limited healthcare infrastructure have created conditions conducive to the emergence and spread of resistant pathogens. Available evidence indicates alarmingly high resistance rates, including reports of up to 97% methicillin resistance among Staphylococcus aureus isolates and over 90% resistance in Escherichia coli to commonly used antibiotics. These findings suggest that many standard treatment regimens may already be compromised. Despite these risks, AMR remains insufficiently prioritized within national health strategies, overshadowed by acute emergencies such as cholera outbreaks, drought, and malnutrition. This commentary synthesizes available evidence on the extent, drivers, and public health implications of AMR in Somalia and highlights its potential regional and global consequences. Urgent and coordinated action is required to strengthen surveillance, improve antimicrobial stewardship, and enhance governance within a One Health framework. Without decisive intervention, Somalia risks becoming a regional reservoir for highly resistant infections.