Annals of Clinical Microbiology and Antimicrobials最新文献

Background: Few studies have investigated the impact of carbapenem-resistant Pseudomonas aeruginosa (CRPA) on long-term outcomes in bronchiectasis. This study aimed to analyze acute exacerbations and mortality in bronchiectasis patients with CRPA isolation.

Methods: This retrospective study included bronchiectasis patients with PA-positive cultures from January 1, 2014, to July 31, 2023, at West China Hospital of Sichuan University. PA was isolated from sputum or bronchoalveolar lavage fluid (BALF) and classified into CRPA and non-CRPA groups based on antimicrobial susceptibility testing. Multivariate logistic regression was used to assess risk factors for acute exacerbations, while multivariate Cox regression identified independent risk factors for all-cause and cause-specific mortality.

Results: Among 564 patients with PA-positive isolates, 143 (25.36%) harbored CRPA strains. CRPA isolation was associated with an increased risk of acute exacerbations (adjusted odds ratio [aOR] 2.072, p = 0.001), while antibiotic treatment reduced the risk of exacerbations (aOR 0.439, p = 0.011). CRPA isolation was an independent risk factor for all-cause (adjusted hazard ratio [aHR] 1.488, p = 0.031) and cause-specific mortality (aHR 1.882, p = 0.010). The 1-, 3-, 5-, and 7-year cause-specific survival rates in the CRPA group were 88.6%, 79.8%, 73.2%, and 68.0%, respectively, versus 95.4%, 91.0%, 85.6%, and 81.8% in the non-CRPA group (p = 0.001).

Conclusion: CRPA isolation was significantly associated with an increasing risk of acute exacerbations, overall and cause-specific mortality. These findings underscored the urgent need to strengthen antibiotic stewardship to reduce the emergence of CRPA and to implement early detection and targeted management strategies to improve outcomes for patients with CRPA.

Background: Skull base osteomyelitis (SBO) is a severe disease not only because of its rapid progression and its high mortality: diagnosis and treatment are often protracted and in more than 30% of cases no causative pathogen can be detected. SBO is usually preceded by immunodeficiency, which is why opportunistic infections caused by atypical pathogens must also be taken into consideration. In consideration of the different possible entities, an interdisciplinary approach with surgical debridement, pathological sampling, microbiological testing and antimicrobiological therapy is indispensable.

Case presentation: We report on a 58-year-old female patient who presented to our clinic for the first time in 2014 with a bilateral skull base osteomyelitis. The patient had a history of several comorbidities, including hypogammaglobulinemia following the successful treatment of a relapsed B-CLL. Different surgical treatments had already been attempted at the time of initial presentation. Several rheumatological, orthopedic, haemato-oncological and divergent microbiological differential diagnoses could be ruled out. Despite various interdisciplinary treatment attempts (including surgery, antibiotic therapies and hyperbaric oxygen therapy) the progress led to a palsy of the caudal cranial nerve group in 2022. With all preceded microbiological sampling being negative, we initiated species specific PCRs covering atypical organisms. An atypical infection of Mycoplasma pneumoniae was detected. After starting antibiotic therapy with azithromycin and doxycycline the progress could be halted and the palsies were regredient. The following MRI scans confirmed a decline in findings.

Conclusions: To the authors' knowledge, this case report is the first description of SBO as an extrapulmonary M. pneumoniae infection. It shows the diagnostic and therapeutic complexity of a multifaceted clinical picture in which immunological, microbial and ENT-surgical diagnostic and therapeutic concepts must be regularly coordinated. Against the background of the high proportion of missing pathogens up to 30%, interdisciplinary cooperation within the framework of the ABS concept is emphasized. Structured and interdisciplinary diagnostics by a skull base center specializing in this field was ultimately decisive for treatment in this case.

Introduction: In times of mold active prophylaxis, invasive aspergillosis (IA) epidemiology is evolving. Presentation in non-neutropenic may differ from neutropenic. We investigated the cases of IA in our center with a focus on differences between neutropenic and non-neutropenic, and analyzed the impact of cryptic and non-fumigatus Aspergillus species.

Methods: Retrospective observational study including all adult patients admitted to the Puerta de Hierro-Majadahonda Hospital between January 2018 and April 2024 with IA.

Results: 112 IA were identified. Only 11 (9.8%) had neutropenia as risk factor for IA. Most frequent risk factors were corticosteroids (77.2%), SOT (46.5%), SARS-CoV2 (29.7%) and CMV replication (28.7%). 89.3% were pulmonary IA with 6 cases (5.4%) of disseminated infection. A. fumigatus was the most frequent species 48 (51.6%). 13 cases (14%) were caused by cryptic Aspergillus spp. Non-neutropenic patients, compared to neutropenic patients, were more likely to have positive fungal cultures (83.2% versus 54.5%, p = 0.023[NS]), and not to present a halo sign (7.4% versus 45.5%, p = 0.003 [NS]). In addition, in non-neutropenic patients, compared to neutropenic patients, there was a trend towards a greater probability of positive GM from BAL (81.3% versus 66.7%, p = 0.304) and a trend towards a lower probability of positive serum GM (25.7% versus 45.5%, p = 0.137). 41/112 (36.6%) cases presented breakthrough IFI and in 51.2%, (21/41 cases), the isolate was resistant to the prior antifungal. One presented A. fumigatus with the TR34-L98H mutation.

Conclusion: Risk factors different than neutropenia are currently the most common in IA. The clinical presentation in non-neutropenic patients differs from neutropenic. Resistance to antifungals is emerging especially in breakthrough IA.

Background: Long COVID is a complex, heterogeneous syndrome affecting over four hundred million people globally. There are few recommendations, and no formal training exists for medical professionals to assist with clinical evaluation and management of patients with Long COVID. More research into the pathology, cellular, and molecular mechanisms of Long COVID, and treatments is needed. The goal of this work is to disseminate essential information about Long COVID and recommendations about definition, diagnosis, treatment, research and social issues to physicians, researchers, and policy makers to address this escalating global health crisis.

Methods: A 3-round modified Delphi consensus methodology was distributed internationally to 179 healthcare professionals, researchers, and persons with lived experience of Long COVID in 28 countries. Statements were combined into specific areas: definition, diagnosis, treatment, research, and society.

Results: The survey resulted in 187 comprehensive statements reaching consensus with the strongest areas being diagnosis and clinical assessment, and general research. We establish conditions for diagnosis of different subgroups within the Long COVID umbrella. Clear consensus was reached that the impacts of COVID-19 infection on children should be a research priority, and additionally on the need to determine the effects of Long COVID on societies and economies. The consensus on COVID and Long COVID is that it affects the nervous system and other organs and is not likely to be observed with initial symptoms. We note, biomarkers are critically needed to address these issues.

Conclusions: This work forms initial guidance to address the spectrum of Long COVID as a disease and reinforces the need for translational research and large-scale treatment trials for treatment protocols.

Background: Ceftazidime/avibactam (CZA)-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae has emerged, typically due to mutations in the bla_KPC gene. This study aimed to investigate the clinical and microbiological characteristics of patients with CZA-resistant KPC-producing K. pneumoniae, with a focus on comparing strains with KPC variants to those with wild-type KPC.

Methods: Unique adult patients with CZA-resistant KPC-producing K. pneumoniae were identified at Taipei Veterans General Hospital between February 2019 and June 2024. Clinical characteristics and outcomes were recorded, and KPC variants were detected using polymerase chain reaction followed by Sanger sequencing.

Results: A total of 60 cases of CZA-resistant KPC-producing K. pneumoniae were included. The 14-day and in-hospital mortality rates were 20% and 41.7%, respectively. Thirty-six strains (60%) harbored KPC variants, with 22 different types identified. KPC-33 (n = 12) was the most common variant. Previous isolation of carbapenem-resistant K. pneumoniae and prior exposure to CZA were more common in the KPC variant group than in the wild-type KPC group. Strains producing KPC variants showed a higher proportion of CZA minimum inhibitory concentration (MIC) ≥ 64 µg/mL (80.6% vs. 4.2%, p < 0.001) and restored meropenem susceptibility (MIC ≤ 4 µg/mL) (72.2% vs. 0%, p < 0.001) compared to those producing wild-type KPC. Additionally, the 14-day mortality rate was lower in patients infected with KPC variant strains compared to those with wild-type KPC strains (11.5% vs. 36.4%, p = 0.041).

Conclusion: CZA-resistant KPC-producing K. pneumoniae is associated with high mortality. Strains producing KPC variants are more likely to exhibit restored meropenem susceptibility and higher levels of CZA resistance.

Background: Endodontic treatment failures are predominantly attributed to Enterococcus faecalis (E. faecalis) infection, a Gram-positive coccus. E. faecalis forms biofilms, resist multiple antibiotics, and can withstand endodontic disinfection protocols. Vancomycin-resistant strains, in particular, are challenging to treat and are associated with serious medical complications.

Methods: A novel phage, vB_EfaS_ZC1, was isolated and characterized. Its lytic activity against E. faecalis was assessed in vitro through time-killing and biofilm assays. The phage's stability under various conditions was determined. Genomic analysis was conducted to characterize the phage and its virulence. The phage, propolis, and their combination were evaluated as an intracanal irrigation solution against a 4-week E. faecalis mature biofilm, using an ex vivo infected human dentin model. The antibiofilm activity was analyzed using a colony-forming unit assay, field emission scanning electron microscopy, and confocal laser scanning microscopy.

Results: The isolated phage, vB_EfaS_ZC1, a siphovirus with prolate capsid, exhibited strong lytic activity against Vancomycin-resistant strains. In vitro assays indicated its effectiveness in inhibiting planktonic growth and disrupting mature biofilms. The phage remained stable under wide range of temperatures (- 80 to 60 °C), tolerated pH levels from 4 to 11; however the phage viability significantly reduced after UV exposure. Genomic analysis strongly suggests the phage's virulence and suitability for therapeutic applications; neither lysogeny markers nor antibiotic resistance markers were identified. Phylogenetic analysis clustered vB_EfaS_ZC1 within the genus Saphexavirus. The phage, both alone and in combination with propolis, demonstrated potent antibiofilm effects compared to conventional root canal irrigation.

Conclusion: Phage vB_EfaS_ZC1 demonstrates a promising therapy, either individually or in combination with propolis, for addressing challenging endodontic infections caused by E. faecalis.

Background: Antimicrobial resistance in Enterobacterales represents a substantial threat in modern clinical practice and the collection of data on the efficacy of new molecules is of paramount importance. Our study aimed to analyse the in vitro activity of imipenem/cilastatin/relebactam (IMI/REL) against KPC-producing Klebsiella pneumoniae (KPC-Kp) and investigate the genetic determinants of resistance to this agent.

Methods: A total of 603 KPC-Kp strains, which were randomly collected during a multicentre study in northern Italy in the period 2016-2018, were analysed retrospectively. Antibiotic susceptibility testing was performed using a commercial broth microdilution. IMI-REL-resistant KPC-Kp strains were further analysed by whole genome sequencing to identify resistance determinants.

Results: Ninety-eight percent of KPC-Kp (591/603) showed in vitro susceptibility to IMI/REL, with a minimum inhibitory concentration below the EUCAST cut-off. Different mutations in OmpK36 were found in all 12 IMI/REL-resistant strains, which belonged to MLST STs 258 (3 isolates), 307 (8 isolates) and 512 (1 isolate), but no clonal relatedness was detected by the minimum spanning tree analysis, except for 2 strains isolated in the same hospital. Equal distribution of bla_KPC-2 (6/12) and bla_KPC-3 (6/12) was found, and in 11 isolates the presence of genetic variants associated with the production of beta-lactamases was also identified. KPC-Kp resistant to IMI/REL retained susceptibility to meropenem/vaborbactam (MVB, 12/12, 100%) and ceftazidime/avibactam (CZA, 11/12, 91.7%). Only one strain of 603 was resistant to either MVB and CZA but susceptible to IMI/REL with a MIC of 2 mg/L; 4/603 (0.7%) were resistant to CZA but susceptible to IMI/REL and MVB.

Conclusions: IMI/REL showed good in vitro activity against the KPC-Kp strains analysed. All the IMI/REL-resistant strains displayed a mutation in porin OmpK36 and produced carbapenemases, with KPC-2 and KPC-3 being equally distributed. MVB and CZA maintained good activity against IMI/REL resistant isolates.

Background: Stratified antibiograms are recommended to guide empiric clinical treatment. However, which strata to focus on, the limited number of isolates in identified strata, and the heavy associated workload all pose challenges. This study compares differences in antibiotic susceptibility between a hospital-wide, all-specimens antibiogram and stratified antibiograms in order to identify the value-added of antibiogram stratification.

Method: Antibiotic susceptibility of bacterial isolates from 2021 at a quaternary-care academic hospital was obtained from published hospital-wide and unit- and specimen-specific stratified antibiograms. Differences in percent susceptibility by organism and drug between the hospital-wide and stratified antibiograms were calculated. Weighted averages of the difference in percent susceptibility were calculated for each stratified antibiogram compared to the hospital-wide antibiogram and unit-wide antibiograms. Differences were shown through heat maps.

Results: When compared to a hospital-wide, all-specimens antibiogram, the emergency department (ED) antibiogram showed higher susceptibility, whereas the intensive care unit (ICU) and, particularly, the transplant unit antibiograms exhibited reduced susceptibility. Compared to unit level antibiograms, further stratification within each unit to specimen-specific (syndromic) antibiograms revealed additional differences. In the ED, urine and respiratory-stratified antibiograms had lower susceptibility and blood had higher susceptibility. Compared to unit-specific antibiograms, in the ICU, all specimen-stratified antibiograms had lower susceptibility and in the transplant unit, antibiograms for all specimens but urine had lower susceptibility.

Conclusion: Using a hospital-wide all-specimens antibiogram may both overcall and under call susceptibility leading to poor empiric antimicrobial choices. Specimen-specific antibiograms stratified by unit best inform empiric therapy for specific populations.