Annals of Clinical Microbiology and Antimicrobials最新文献

Background: Morganellaceae (including Proteus, Providencia, and Morganella) are opportunistic pathogens increasingly associated with antimicrobial resistance (AMR). Long-term trend data, particularly from the Middle East, remain scarce. This study aimed to characterize the epidemiology, demographic and clinical characteristics, and antimicrobial resistance dynamics of Morganellaceae isolates in southern Saudi Arabia over a 12-year period, with a specific focus on carbapenem resistance (CRE), multidrug resistance (MDR), and difficult-to-treat resistance (DTR), as well as their genus-level variability and unique resistance phenotypes.

Methods: A 12-year retrospective cross-sectional study (2012-2024) was conducted at Aseer Central Hospital, southern Saudi Arabia. Non-duplicate clinical isolates from patients ≥ 12 years were identified using VITEK^® 2, with susceptibility interpreted according to CLSI guidelines. CRE, MDR, and DTR were defined by standardized criteria. Logistic regression was applied to model annual non-susceptibility trends, reported as odds ratios (ORs) and annual percent change (APC). Subgroup analyses explored genus-level differences, ICU versus non-ICU settings, and intra-genus variability.

Results: A total of 3,338 isolates were recovered, predominantly Proteus spp. (72.4%), followed by Providencia (18.6%) and Morganella (9.0%). Overall prevalence of CRE, MDR, and DTR was 25.7%, 44.8%, and 13.2%, respectively. Providencia showed the highest resistance burdens (CRE 33.6%, MDR 68.1%, DTR 23.2%), significantly exceeding Proteus (CRE 23.3%, MDR 39.1%, DTR 10.0%) and Morganella (CRE 29.3%, MDR 42.3%, DTR 9.2%) (all p < 0.001). Within CRE, 32.8% of isolates were non-susceptible to imipenem yet remained susceptible to meropenem and ertapenem. Compared with non-ICU isolates, ICU isolates exhibited higher MDR (49.6% vs. 41.5%, p < 0.001) but lower CRE (23.1% vs. 27.5%, p = 0.006), while DTR prevalence was comparable. Temporal analysis demonstrated significant declines in resistance to cephalosporins, fluoroquinolones, aminoglycosides, and Trimethoprim-Sulfamethoxazole, whereas imipenem resistance rose sharply (APC + 48.6%; OR 1.49, 95% CI 1.43-1.54, p < 0.001); meropenem and ertapenem remained stable.

Conclusions: Morganellaceae infections in southern Saudi Arabia carry substantial MDR and CRE burdens with pronounced genus-level variability,with Providencia posing the greatest therapeutic challenge. While several antibiotic classes showed declining resistance, the sharp rise in imipenem non-susceptibility is concerning. Strengthening species-level AST reporting and integrating Morganellaceae resistance data into healthcare-associated infection (HAI) surveillance frameworks are essential, particularly in ICU settings where outbreak risk is greatest.

Background: The incidence of drug-resistant candidiasis has increased in recent decades, leading to significant treatment challenges and high morbidity and mortality rates. The development of new therapeutic options is crucial, but it is a complex and time-consuming process; an interesting strategy to face this problem is to combine existing antifungal drugs with synergistic agents to enhance treatment efficacy, reduce dosage and prevent resistance development.

Methods: We analyzed the activity of lactoferrin against 80 isolates of 14 Candida species, including Candida auris according to both EUCAST and CLSI guidelines. Moreover, interaction between fluconazole and lactoferrin was assessed by checkerboard method against a selection of 38 isolates of eight Candida species, and by time-kill curves against six isolates of two Candida species, including fluconazole susceptible and resistant isolates.

Results: Synergistic and additive effects were demonstrated, with effective inhibition of Candida growth. Furthermore, combination therapy significantly reduced fluconazole minimum inhibitory concentrations (MICs) and showed synergistic effect against fluconazole-resistant isolates.

Conclusions: Lactoferrin has significant potential value in the treatment of candidiasis and further exploration of its potential clinical applications is of great importance. The ability of lactoferrin to enhance the efficacy of existing antifungal drugs while potentially reducing the development of antifungal resistance makes it an intriguing candidate for future research and development efforts.

Background: Bloodstream infections remain a major cause of morbidity and mortality worldwide, with the increasing threat of antimicrobial resistance (AMR) complicating treatment options. This study aimed to describe the frequency, distribution, and patterns of AMR among blood culture isolates over 5 years at the University Teaching Hospital of Kigali, in Rwanda.

Methods: A retrospective cross-sectional surveillance analysis was performed on 1352 bacterial isolates from 8301 blood cultures conducted between January 1, 2020, and December 31, 2024. The distribution of pathogens, antimicrobial resistance profiles, and comparisons of resistance patterns between isolates from outpatient and hospitalized patients were analyzed using SPSS version 28. A p-value less than 0.05 was considered statistically significant.

Results: The most common isolates were Staphylococcus aureus (37.2%), Klebsiella pneumoniae (22.4%), Escherichia coli (13%), and Acinetobacter baumannii (11.6%). Nearly all isolates originated from inpatients (98.6%), with the pediatric unit accounting for 40.7%. Alarmingly high resistance rates were observed for ampicillin (94.2%), amoxicillin-clavulanic acid (92.5%), third-generation cephalosporins (79-86%), and ciprofloxacin (58.7%). Notably, vancomycin (1%) for Gram-positive bacteria, and polymyxin B (27.1%), imipenem (25.5%), and amikacin (15.6%) for Gram-negative bacteria generally exhibited lower resistance rates. Additionally, AMR was significantly more prevalent in isolates from hospitalized patients compared to ambulatory patients (p < 0.0001).

Conclusion: This study reveals a substantial burden of AMR in blood culture isolates, particularly affecting hospitalized and pediatric patients. The high resistance rates to commonly used antibiotics highlight an urgent need for strengthened antimicrobial stewardship programs, improved infection prevention measures, and enhanced diagnostic laboratory capacity to guide therapy.

Background: The persistent spread of multiple drug-resistant tuberculosis (MDR-TB) is one of the most pressing and challenging issues facing the global TB control efforts. Standard first-line treatment for MDR TB is nearly ineffective for patients infected with strains of the disease that are resistant to isoniazid and rifampicin.

Objective: To assess the magnitude of poor MDR-TB treatment outcomes among MDR-TB patients at the MDR-TB clinic, tertiary Hospital, Southwest, Ethiopia.

Methods: A retrospective cross-sectional study was conducted at the MDR-TB clinic, Mattu Karl Comprehensive Specialized Hospital (MKCSH), from 2018 to 2024. A data collection checklist was used to collect information on sociodemographic, clinical characteristics, medication, and treatment outcomes from the patient's medical cards. The collected data were cleaned, coded, entered, and analyzed using SPSS version 20 computer software. Descriptive data analysis was done to describe variables by percent and frequency. Data were presented in tables and pie charts.

Result: A total of 72 (54.2% male and 47.8% female) MDR-TB patients were included in this study analysis. Among a total, 54.2% were men. The mean age of the patients was 31.42 years with a standard deviation of 7.81 years, and 25% were positive for human immunodeficiency virus (HIV). The most common adverse drug reaction was gastric disturbance (45.8%). The majority, 79.2% had a successful outcome: 75% were cured and 4.2% have completed treatment. The magnitude of poor MDR-TB treatment outcome was 20.8%: 12.5% were death and 8.3% defaulted from treatment.

Conclusion: The magnitude of poor MDR-TB treatment outcomes among MDR-TB patients was high. Strengthening patient support systems and optimizing treatment protocols are essential strategies to reduce the prevalence of poor outcomes.

Backgroud: To investigate the preventive effects of combined live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus cereus tablets (CBLEBTL) on patients with radiation pneumonitis associated with CyberKnife treatment for pulmonary malignancies.

Methods: In total, 130 patients who received CyberKnife treatment for pulmonary malignancies at the First Hospital of Hebei Medical University between August 2023 and February 2025 were enrolled. Patients were randomly categorized into the experimental group (n = 65) or control group (n = 65). While both groups received CyberKnife treatment for pulmonary lesions, the experimental group additionally received CBLEBTL (0.5 g/dose, thrice daily). The primary endpoint was to determine the incidence of RP, and secondary endpoints included onset time of RP and Eastern Cooperative Oncology Group performance status (ECOG PS) scores.

Results: RP incidence was significantly lower in the experimental group (6/61 [9.8%]) than in the control group (16/62 [25.8%]) (χ² = 5.340, P = 0.021). The mean onset time of RP was significantly delayed in the experimental group than in the control group (176.9 vs. 166.6 days; hazard ratio = 0.34, 95% confidence interval: 0.15-0.80, P < 0.05). ECOG PS of the experimental group was significantly lower than that of the control group at 2, 4 and 6 months post-CyberKnife treatment (P < 0.05).

Conclusion: CBLEBTL effectively reduced the incidence of CyberKnife-associated RP among patients with pulmonary malignancies, delayed RP onset, and improved their quality of life.

Trial registration: This prospective trial was registered retrospectively (after patient enrollment began) because of delays in institutional approval processes. The retrospective registration was approved by the Ethics Committee of The First Hospital of Hebei Medical University (Approval No. [2025]074). The trial is registered at: WHO-primary registry ChiCTR (No. ChiCTR2500104615; Date: 19-Jun-2025), accessible via WHO ICTRP ( https://trialsearch.who.int/ ); China's National Public Health Security Information Platform (No. MR-13-25-043029; Date: 09-Jun-2025). All study procedures followed the original protocol without modifications.

Background: Pulmonary tuberculosis (PTB) diagnosis primarily relies on sputum examination, which can be challenging for patients unable to produce sputum. Minimally invasive oral sampling methods, such as tongue swabs (TS), have been proposed as alternatives. We assessed the effectiveness of TS for PTB diagnosis using molecular tests.

Methods: In a prospective study at two TB clinics, 99 confirmed smear-positive PTB patients provided 11 TS and one additional sputum sample (SS) for GeneXpert-Ultra (Ultra) testing at the National Reference Laboratory for Mycobacteriology. Testing was performed on a single TS (1TS), three pooled TS (3TS), and the additional SS. Additionally, we retrospectively analyzed TS from 120 participants with TB symptoms using an in-house IS6110-qPCR at the Institute of Tropical Medicine, alongside two SSs tested by fluorescence microscopy, GeneXpert-MTB/RIF (Xpert) and Ultra in Guinea.

Results: In the prospective study, among 99 smear-positive patients, Ultra detected Mycobacterium tuberculosis (MTB) in 86.9% (1TS) and 91.9% (3TS), compared to 96.9% in SS. The highest positivity grade for sputum was "MTB detected high" (n = 31) with no "Trace" results, while for any TS the maximum grading was "Medium". TS positivity grades were mostly "MTB Low", and was not impacted by the sample swab number tested. In the retrospective study, positivity rates for sputum were 35% on microscopy, 44% on Xpert, 38.6% on Ultra, and 38.3% on in-house swab-IS6110-qPCR, with strong agreement between sputum-Xpert/Ultra and swab-IS6110-qPCR (k = 0.91 Xpert, k = 0.86 Ultra).

Results: TS demonstrated its ability to detect MTB on molecular tests, providing a minimally invasive complement for PTB diagnosis. Further studies in sputum scarce patients are needed.

Background: The rise of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) strains represents a major clinical threat, particularly in Asia. These strains possess both extensive drug resistance and enhanced virulence traits, leading to high morbidity and mortality. This study aimed to characterize the genomic profile of a CR-hvKp isolate (BB-7) obtained from a clinical case in eastern India and to investigate its resistance and virulence mechanisms.

Methods: K. pneumoniae BB-7 was obtained from the urine sample of a 75-year-old male and identified by using the VITEK2 system and ITS-PCR amplification. Hypervirulence was confirmed through the string test and detection of the iucA gene. The antimicrobial susceptibility (AST) was determined by the Kirby-Bauer disk diffusion method, whereas colistin susceptibility was measured using broth microdilution. Whole-genome sequencing was performed using Illumina NovaSeq, followed by de novo assembly, annotation, and resistome/virulome analysis using tools including PROKKA, CARD, ResFinder, and VFAnalyzer. MLST, plasmid typing, capsular serotyping, phage element, and insertion element were analyzed by using an online database. Phylogenetic analysis was performed using cgMLST and core SNP approaches.

Results: BB-7 exhibited an extensively drug-resistant (XDR) phenotype, including resistance to β-lactams, fluoroquinolones, aminoglycosides, tetracyclines, and colistin. Resistance genes identified included bla_CTX-M-15, bla_SHV-28, bla_TEM-1, bla_OXA-232, bla_OXA-1, armA, aadA2, and others. The virulence profile revealed genes such as iucABCD, iutA, iroEN, and T6SS clusters. Plasmid analysis identified IncHI1B, ColKP3, and IncFIB(K), contributing to the convergence of resistance and virulence. The Capsular serotype at K-locus and O-locus is K64 and O2α.1, respectively. The isolate was assigned a novel sequence type, ST7947 (gapA-1, infB-6, mdh-1, pgi-1, phoE-749, rpoB-46, tonB-1), differing from ST2096 by one allele phoE. Phylogenetic analysis revealed that BB-7 was closely related to ST2096 MDR K. pneumoniae isolates from an Indian hospital.

Conclusion: BB-7 represents a novel CR-hvKp strain with a unique ST7947 genotype, exhibiting co-resistance and hypervirulence, raising concern for public health. The association of high-risk resistance plasmids with virulence factors underscores the urgent need for enhanced genomic surveillance, infection control, and devising specific therapies to restrict the proliferation of such strains.

Background: The strikingly rapid increase in multidrug-resistant Acinetobacter baumannii (MDRAB) incidence rates represents a major challenge in healthcare settings. This is due to the limitation of the currently available treatment options to combat tenacious A. baumannii infections. MDRAB isolates belonging to recently emerged global clones GC9 and GC10 are on the rise, especially in the Middle East and Africa, which warrants a thorough investigation of these global clones.

Methods: Thirteen A. baumannii isolates belonging to less well-studied global clones were selected from 46 isolates collected in Alexandria, Egypt, after determining their clone using MLST. Susceptibility to multiple antibiotic classes was determined by the Kirby-Bauer disk diffusion method. Testing of carbapenemase activity and selected virulence phenotypes was done. Whole genome sequencing, phylogenetic analysis, and molecular characterization of the resistance and virulence genotypes were performed. Checkerboard assay was employed for testing the combination of each of ciclopirox and N-acetylcysteine (NAC), as potential repurposed drugs, with each of meropenem and levofloxacin antibiotics against MDRAB isolates.

Results: All the isolates displayed multidrug resistance and were carbapenemase-positive. One isolate showed strong biofilm formation, whereas 4 and 8 isolates were moderate and weak biofilm formers, respectively. Twelve out of thirteen isolates were positive twitchers. The isolates showed moderate phospholipase and strong protease activities. However, low phospholipase production was detected in one isolate. The genomic analysis revealed that 3 and 10 isolates belonged to ST85 (GC9) and ST158 (GC10), respectively. All 13 isolates harbored multiple resistance genes including oxa23 and carried an RP-T1 rep type plasmid. Phylogenetic analysis demonstrated that the isolates were clustered together forming subclades with others from Alexandria/Egypt. The AbGRI3-2 resistance island (RI) was detected in ST158 isolates carrying R3-T60 rep type and 9 antibiotic resistance genes. The combination of NAC with each of meropenem or levofloxacin showed a synergistic action against 3 and one isolate(s), respectively, using the checkerboard assay.

Conclusion: The current study provides an in-depth characterization of the collected MDRAB isolates from the global clones GC9 and GC10. The endemicity of these clones necessitates strategies to mitigate ongoing MDRAB outbreaks in countries like Egypt. Combination of NAC with meropenem or levofloxacin represents a promising treatment option against the newly emerged global clones that needs further in vivo testing.

Background: Nitrofurantoin is an antibiotic that demonstrates good efficacy in the treatment of uncomplicated urinary tract infections (UTIs), especially those caused by uropathogenic Escherichia coli (UPEC). However, recent reports about the emergence of nitrofurantoin resistance in UPEC are concerning. This study aimed to investigate the genetic diversity of nitrofurantoin-resistant UPEC isolates and their characteristics.

Methods: In this cross-sectional study, 235 UPEC isolates collected from Ahvaz, Iran were investigated for resistance to nitrofurantoin. To evaluate the mechanism of this resistance, two groups of chromosomal genes (nfsA, nfsB, and ribE) and plasmid genes (oqxA and oqxB) were investigated by PCR. The nfsA, nfsB, and ribE genes were sequenced and variations of them were analyzed. The phenotypic and genotypic characteristics of the isolates were investigated.

Results: In total, six (2.55%) nitrofurantoin-resistant UPEC isolates were identified. The oqxA and oqxB genes and mutations in ribE were not detected. Several deleterious mutations in NfsA (G130D, S39G, H11Y, and ΔW77-F79), and NfsB (N42H, W46R, and H80Y), as well as several neutral mutations in both genes were detected. To our knowledge, the NfsB mutations N42H and H80Y have not been previously reported, suggesting potential novelty. All these isolates were multidrug-resistant (MDR). Although all were non-motile and non-hemolytic, some showed biofilm and cellulose production. Three isolates belonged to the B2 group, while the others belonged to the B1, A, and F groups. Pathogenicity islands (PAIs) IV₅₃₆, I_CFT073, II_CFT073, and I₅₃₆ were variably present. Incompatibility plasmid replicons Frep, FII, FIA, FIB, I1, and A/C were detected across isolates. Virulence-associated genes (VAGs) including iutA, fyuA, papG, traT, fimH, kpsMT II, papC, and afa/draBC were identified.

Conclusion: We concluded that in our studied isolates, deleterious mutation in chromosomal genes nfsA, nfsB, or both is likely drivers of resistance to nitrofurantoin and the changes caused by gene ribE and the presence of plasmid genes oqxAB are at the next levels of importance. Examination of the phenotypic and genetic characteristics of the isolates demonstrates that these mutations may occur in some isolates with high antimicrobial resistance and virulence, highlighting the need for broader studies to assess their epidemiological significance.

Diagnosis of prosthetic Joint Infections (PJI) remains challenging at the microbiological level. Despite the implementation and adoption of new methods, an heterogeniety of microbiological practices is still observed. These CRIOGO recommendations (Centre de Référence des Infections Ostéo-articulaires du Grand Ouest) aim to set out some basic principles for the diagnosis of PJI in microbiology laboratories. The CRIOGO microbiologists' team who have been working together for 15 years were invited to provide regional recommendations for microbiology diagnosis based on their practical expertise. These recommendations were developed through a systematic review of the literature and discussion amongst experts. The proposed CRIOGO recommendations were voted on upon by a 10 local panelists via the Delphi process. Total consensus was reached on all 27 recommendations that received 100% agreement. The CRIOGO microbiologists' team proposed practical guidelines in response to the most frequently asked questions received at our laboratory reference centres. A short, comprehensive answer supported by literature backs up the argument. Out of the 27 detailed CRIOGO recommendations, 22 achieved 100% consensus. This work was initiated to harmonise our daily practices for managing PJI diagnosis within the CRIOGO network in line with the literature.