Annals of Clinical Microbiology and Antimicrobials最新文献

Tuberculosis (TB) remains a significant global health issue, with drug-resistant TB posing a major challenge. The genetic lineage of Mycobacterium tuberculosis (Mtb) is known to influence various aspects, including drug resistance. Still, the relationship between different lineages and drug resistance levels, especially in the context of the Beijing genotype, requires further exploration. This study aimed to investigate the disparities in drug resistance among diverse lineages of Mtb. We analyzed 193 clinical isolates from drug-resistant TB patients, among them 91.2% were MDR/pre-XDR-TB. Samples were collected from patients at specific hospitals between 2014 and 2020. The isolates were subjected to smear microscopy, sputum culture, minimum inhibitory concentration (MIC) testing, and whole-genome sequencing (WGS). The MIC distributions and resistance levels of drugs like INH, AMK, RIF, EMB, and FQ were analyzed, and the association between lineages and drug resistance was determined using statistical tests. Our results showed significant differences in the MIC distributions and resistance levels of INH and AMK between lineages 2.2 and 2.3. Lineage 2.3.2 was a protective factor for high-level INH resistance, and lineage 2.3 was a protective factor for high-level AMK resistance. The L2.3.6 strain had a high proportion of high-level resistance to INH and AMK. This study provides evidence for the evolution and spread of the modern Beijing genotype of Mtb. It suggests that L2.3.6 will have the potential to become the main sublineage of tuberculosis for the spread of drug-resistant tuberculosis and the necessity of pedigree testing of drug-resistant strains in clinical treatment.

Background: Since the incidence of vancomycin-resistant enterococci (VRE) is increasing and treatment options remain limited, we aimed to investigate the epidemiology of vancomycin- and tigecycline-resistant enterococci in a university hospital using whole genome sequencing (WGS).

Methods: Between April and December 2021, 102 VRE isolates were collected from a single tertiary care hospital in the Czech Republic. Forty selected isolates underwent antimicrobial susceptibility testing and WGS (Illumina short reads and long reads with MinION in selected isolates).

Results: All Enterococcus faecium isolates were resistant to ampicillin, carrying the PBP5_Met485Ala, PBP5_Glu629Val, and fluoroquinolones carrying the GyrA_Ser83Ile and ParC_Ser80Ile substitutions. The vanA operon was found on pELF2-like plasmids and plasmids carrying rep17 and/or rep18b genes. The novel Tn1546 structural variants were identified in vanA-carrying isolates. The vanB operon was located on the chromosome within a Tn1549 structural variant. Linezolid resistance was detected in one isolate carrying the 23S rDNA_G2576T substitution. Twenty-two isolates were resistant to tigecycline (tet(L), tet(M) and rpsJ_del 155-166 or RpsJ_Lys57Arg). Discrepancies between phenotypic and genotypic resistance profiles were observed for daptomycin (RpoB_Ser491Phe), trimethoprim/sulfamethoxazole (dfrG gene), nitrofurantoin (NmrA_Gln48Lys substitution without the EF0404 and EF0648 genes) and tetracycline (truncated TetM). The two multilocus sequence typing (MLST) schemes identified different numbers of STs: 5 STs, with ST117 as the predominant one (n = 32, 80%), versus 10 STs, with ST138 (27.5%), ST136 (25%), and ST1067 (20%) being the most frequent, respectively. The whole genome MLST revealed clonal clustering (0-7 allele differences) among isolates of the same ST. When comparing ST117 isolates from our study with 2,204 ST117 isolates from 15 countries, only one Czech isolate clustered closely with strains from Germany and the Netherlands, differing by just 16 alleles.

Conclusions: The spread of E. faecium isolates ST117 resistant to vancomycin and tigecycline was identified. The discrepancies between resistance genotypes and phenotypes highlight the importance of combining molecular and phenotypic surveillance in antimicrobial resistance monitoring.

Objectives: To investigate the mechanisms of ceftazidime/avibactam (CZA) resistance and the nosocomial dissemination of carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Klebsiella pneumoniae (CRKP) in an intensive care unit (ICU) in China.

Methods: Clinical CRPA and CRKP isolates were obtained from an ICU of a tertiary hospital in China from August 2020 to February 2021. Antimicrobial susceptibility was determined according to CLSI. WGS, cloning experiments and kinetic parameters were conducted to reveal resistance mechanisms, molecular characteristics and dissemination of CRPA and CRKP.

Results: We isolated 32 CZA-resistant strains, including 12 CRPA and 20 CRKP strains from an ICU between August 2020 and February 2021. CZA resistance was associated with the presence of NDM and efflux pumps in CRKP strains, whereas bla_AFM-2, bla_KPC-87, and bla_PER-1 contributed to CZA resistance in CRPA strains. Compared to KPC-2, KPC-87 exhibited a 1.5-fold elevation in k_cat/K_m for ceftazidime, a 7.5-fold increase in K_i for avibactam, and a loss of carbapenem hydrolysis. bla_KPC-87 was located in the NTE_KPC-IIa like element based on the Tn3. Insertion of 656 bp Δbla_TEM-1 upstream of bla_KPC-87 introduced an additional promoter that increased KPC-87 expression. Cluster 2 and 3 of CRKP represented two different clones of ST11 transmitted between patients. KPC-87-producing ST270 CRPA strains exhibited a small-scale dissemination and cross-regional transfer with the referral of a patient. The evolutionary pathways of AFM-2-producing ST275 CRPA strains were more complex to elucidate the transmission events.

Conclusions: In CRKP and CRPA, diverse resistance mechanisms contributed to CZA resistance. These CZA-resistant strains were transmitted among patients in the ICU and even across regions to the other healthcare unit when the patient was transferred.

Background: To address the overuse of antibiotics, this study examined the clinical characteristics and outcomes associated with antibiotic duration and carbapenem-sparing regimens in hematological patients with Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) bloodstream infections (BSI).

Methods: We conducted a retrospective analysis of hematological patients with E. coli or K. pneumoniae BSI from 2017 to 2023. Propensity score matching (PSM) controlled for confounding variables, and data were analyzed using multivariate regression models.

Results: A total of 1,862 patients were included (E. coli: n = 932; K. pneumoniae: n = 930). Among 1,105 patients in the antibiotic duration cohort, 48.96% (n = 541) received short-course therapy (median: 8 days, IQR: 7-9), while others received prolonged-course therapy (median: 14 days, IQR: 12-17). No significant differences in 30-day mortality or 90-day recurrence rates were observed between the two groups, either before or after PSM. In the antibiotic regimen cohort (n = 1,606), we assessed the effectiveness of carbapenem-containing versus carbapenem-sparing regimens, as well as monotherapy versus combination therapy. Among 1,488 patients with non-carbapenem-resistant Enterobacteriaceae (non-CRE) infections, 567 had infections caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria. In this subgroup, 30-day mortality rates also showed no significant differences between carbapenem-containing and carbapenem-sparing regimens, both before and after PSM.

Conclusion: In conclusion, short-course antibiotic therapy is as effective as prolonged therapy for treating E. coli and K. pneumoniae BSI in hematological patients. Similarly, carbapenem-sparing regimens are non-inferior to carbapenem-based regimens. These findings highlight the potential for optimizing antibiotic use, but further validation through randomized controlled trials is warranted.

Background: Oral bacteria have been associated with several systemic diseases, and studies have highlighted their potential role in carcinogenesis. A biofilm is considered an antimicrobial resistance gene reservoir, and the oral cavity provides an excellent environment for biofilm formation. The aim of this study was to evaluate the pathogen spectrum and antimicrobial resistance rates of clinical isolates from head and neck infections in the Hungarian population.

Methods: A total of 5185 bacterial isolates were analyzed from 1978 patients between 2018 and 2023. Antimicrobial resistance rates were reported according to the EUCAST guidelines. The primary diagnoses of the patients were categorized into three major groups: abscesses, necrotizing lesions and surgical site infections of patients treated for malignant tumors. Pearson's chi-square test was used to compare the percentages of bacteria in the different patient groups.

Results: The most frequently isolated bacteria were Streptococcus (18.8%) and Prevotella spp. (13.5%), followed by Staphylococcus (13.2%) and Fusobacterium spp. (9.1%). Differences in the pathogen spectrum of three patient groups ('abscess', 'necrosis' and 'tumor') were also evaluated. Compared with the other two patient groups, cancer patients had significantly greater percentages of Enterobacter spp., Enterococcus spp., Pseudomonas spp. and beta-hemolytic streptococci. Substantial resistance rates to clindamycin were observed for Prevotella, Streptococcus and Staphylococcus spp. at 40.9% (95% CI [37.3-44.7%]), 34.8% (95% CI [31.8-37.9%]) and 32.3% (95% CI [28.8-35.9%]), respectively. The percentage of methicillin-resistant Staphylococcus aureus isolates was 13.8% (95% CI [9.2-19.5%]). The percentage of vancomycin-resistant Enterococcus spp. isolates was 2.8% (95% CI [0.6-8.0%]), and the percentages of extended-spectrum beta-lactamase-producing E. coli and Klebsiella spp. isolates were 1% (95% CI [0.02-5.6%]) and 2.6% (95% CI [0.8-5.9%]), respectively.

Conclusion: Our evaluation revealed high percentages of Enterobacterales in patients with diseases such as osteonecrosis or oral cancer. Further investigation of the role of the oral microbiota and its potential impact on the morbidity of patients with advanced disease is needed. Substantial antimicrobial resistance rates, particularly to clindamycin, pose a major concern for treating bacterial infections in the head and neck region.

Background: This study examines colistin resistance in Gram-negative bacteria in Egypt, analyzing prevalence, trends, geographic variations, colistin-carbapenem resistance correlation, and mcr-mediated plasmid resistance.

Methods: We conducted a systematic search of articles published between 2014 and 2024 that reported on colistin or mcr-mediated resistance in Gram-negative bacteria isolated from human infections in Egypt, with clearly defined susceptibility testing methods. A random-effects meta-analysis was conducted to estimate colistin resistance prevalence based on broth microdilution (BMD) findings, the gold standard method. To explore the influence of study-level factors-including alternative susceptibility testing methods-a multivariate meta-regression analysis was performed. The results of the meta-regression are reported as regression coefficients (β), representing the difference in colistin resistance, expressed in percentage points. All statistical analyses were conducted using R software.

Results: This analysis included 55 studies. Based on BMD susceptibility testing, colistin resistance was observed in 9% of all recovered Gram-negative isolates (95% CI: 6-14%) and was significantly higher among carbapenem-resistant isolates (31%, 95% CI: 25-38%), with p < 0.001. Multivariate meta-regression analysis further confirmed that colistin resistance was significantly higher in carbapenem-resistant isolates compared to the total recovered isolates (β = 9.8% points, p = 0.001). Additionally, colistin resistance has significantly increased over time, with a β = 1.8% points per year (p = 0.001). The use of the VITEK 2 system was associated with lower detected colistin resistance compared to BMD (β = -7.0, p = 0.02). Geographically, resistance rates were higher in Upper Egypt (β = 9.3, p = 0.04). Regarding mcr plasmid-mediated resistance, mcr-1 was the most prevalent resistance gene, particularly in E. coli. In contrast, mcr-2 was rare, detected sporadically in K. pneumoniae and P. aeruginosa.

Conclusion: In Egypt, BMD testing identified colistin resistance in 9% of Gram-negative bacteria, increasing to 31% in carbapenem-resistant isolates. This higher resistance in carbapenem-resistant strains suggests stronger selective pressure from frequent colistin use. Additionally, colistin resistance has shown a rising trend over time, likely driven by increased usage and the spread of plasmid-mediated resistance. These findings underscore the urgent need for strict antimicrobial stewardship and alternative therapies to curb resistance evolution.

Background: WHO strategy to end Tuberculosis (TB) calls for drug susceptibility testing of Mycobacterium tuberculosis (MTB) for all patients, in high TB burden settings. Thus, this study aimed to investigate the MTB drug resistance profiles and related risk factors among patients presenting to the Antituberculosis Center of Brazzaville, Republic of Congo.

Methods: A cross-sectional study was carried out from July 2022 to August 2023 involving 1,121 presumptive pulmonary tuberculosis patients enrolled to the Antituberculosis Center of Brazzaville. Sputum samples were collected from all the study participants for the diagnosis of tuberculosis and rifampicin resistance, using the Xpert MTB/RIF (Cepheid, USA) assay. Samples positive for MTB with drug resistance to RIF were further tested for the second line anti-MTB drug susceptibility using the 10-color Xpert MTB/XDR assay.

Result: Out of 1,121 presumptive TB patients tested, 302/1,121 (26.9%) were MTB positive. Among these, 18/302 (6.0%) had received previous TB treatment and 15/302 (5.0%) were HIV co-infected. The mean age of the study population was 34 years, with a higher prevalence in males (69.2%). Of the MTB isolates, 25/302 (8.3%) were Rifampicin-resistant, with 24/25 (96%) further confirmed as multi-resistant strains, including 6/24 (25%) pre-XDR. Risk factors for MDR-TB included a history of TB treatment (AOR = 8.96, p = 0.002) and chronic cough (AOR = 7.14, p = 0.003).

Conclusions: This study reveals a high level of drug-resistant tuberculosis in Brazzaville, with previous TB treatment being a significant risk factor. The findings underscore the need to strengthen molecular surveillance and TB management and control measures in the Republic of Congo.

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.