European Journal of Clinical Microbiology & Infectious Diseases最新文献

Purpose: The evolution of new carbapenemase variants is alarming. We aimed to investigate the genetic context and molecular epidemiology of the emerging OXA-484 carbapenemase in the United Arab Emirates, to decipher its resistance mechanisms and evolutionary relationships.

Methods: Antimicrobial susceptibility testing was performed for an E. coli isolate recovered from an intrauterine contraceptive device of a patient returning to the UAE after a trip to Pakistan. Whole genome sequencing was used to characterize the genetic environment of bla_OXA-484, resistance and virulence determinants. Southern blotting was used to localize OXA-484 gene. Phylogenetic analysis established the sequence type (ST) and used to investigate relationships with global strains, and differences from other OXA-48-like types.

Results: The strain demonstrated selective resistance against ertapenem while maintaining susceptibility to imipenem and meropenem. OXA-484 exhibited R214G substitution affecting the enzyme's activity and distinguishing it from closely related variants like OXA-181 (214R) and OXA-232 (214 S). bla_OXA-484 was located on two non-conjugative plasmids (∼ 65 and 100 kb) within a genetic environment containing multiple insertion sequences. It belonged to the high-risk clone ST167, recognized for its enhanced capacity to acquire and maintain resistance determinants. The gene was mostly prevalent in the Western part of the world with limited distribution in the Middle East.

Conclusion: This study presents the first comprehensive characterization of OXA-484-producing E. coli ST167 in the UAE. The presence of bla_OXA-484 in high-risk clone warrants concern on its dissemination potential and underscores the importance of genomic surveillance and targeted infection control to prevent the spread of emerging resistance determinants.

Unusual non 1a/1b HCV 1 subtypes are mostly prevalent in Sub-Saharan Africa. These variants harbour resistance associated substitutions as natural polymorphisms in the NS5A region and are difficult to characterize and treat. We report the HCV genome sequences from two African subjects with unusual subtype 1 g and 1e treated with the pangenotypic regimen sofosbuvir/velpatasvir with failure in the latter. Sequence analysis of different regions of the HCV genome in a subtype 1 reference panel and use of multiple subtyping tools showed that the NS5A region is the most suitable to detect these unusual HCV subtypes and assist treatment choices.

Pathogen identification is key to the management of periprosthetic joint infection (PJI). Staphylococcus epidermidis is a major cause of PJI. Differentiating between invasive and contaminating S. epidermidis from joint specimens is challenging, and usually S. epidermidis is only considered a true invasive isolate when grown from two or more independent tissue samples. Thus, the detection of S. epidermidis in single synovial fluid (SF) samples from preoperative athrocentesis makes it difficult to draw definitive conclusions about its clinical significance, especially when grown from contamination-prone broth enrichment cultures (BEC). This study evaluates the diagnostic value of S. epidermidis detection in preoperative synovial cultures for the diagnosis of S. epidermidis-related PJI diagnosed by intraoperative tissue culture (TC). A total of 292 patients were included in the study, of whom 271 had prosthetic joint infection (PJI) according to EBJIS criteria. Preoperative synovial fluid (SF) cultures detected Staphylococcus epidermidis in 32.5% cases (SF-epi), other pathogens in 43.2% cases (SF-other), and were negative in 24.3%. Intraoperative tissue cultures TC identified clinically significant S. epidermidis in 30.1% of cases. The overall agreement between SF and tissue cultures was 66.1%, and the presence of S. epidermidis in SF was confirmed by TC in 70.5%. The diagnostic accuracy of SF cultures for S. epidermidis PJI was 83.2%, with sensitivity of 76.1% and specificity of 86.3% to detect S. epidermidis PJI. The positive likelihood-ration (LR+) was 5.5. When S. epidermidis from SF-BEC were excluded from analysis, specificity increased to 94.2%, and LR + was 7, but diagnostic sensitivity dropped to 40.5%. This study highlights the important value of using preoperative SF fluid cultures for the diagnosis of S. epidermidis PJI. The integration of BEC improves diagnostic accuracy and sensitivity in S. epidermidis PJI, and thus providing valuable information to guide clinical practice. For definitive antibiotic treatment decisions intraoperative tissue cultures remain mandatory.

The emergence of antimicrobial resistance (AMR) has been designated as a global threat by the World Health Organization. To combat AMR in Belgium, the Belgian Antibiotic Policy Coordination Committee (BAPCOC) has, among others, developed guidelines for the appropriate use of antimicrobials in the ambulatory practice. We aim to assess the current guidelines from an antimicrobial stewardship perspective and procide suggestions for improving the ambulatory antibiotic guidelines for first-line healthcare providers. The 2022 BAPCOC guidelines were independently evaluated by 7 antimicrobial stewardship experts based on the five "Ds" of antimicrobial stewardship. The results were aggregated, summarized, and consensus was sought. Recommendations improving the guidelines were formulated. A total of 52 recommendations were made, covering 16 different (sub)chapters. The most frequently covered topics were urinary tract infections, followed by skin and soft tissue infections. Among the top five recommendations deemed to have the greatest impact on antimicrobial stewardship outcomes, three were related to the diagnosis or treatment duration of urinary tract infections. Tailoring infectious disease and antibiotic treatment guidelines to antimicrobial stewardship principles and the latest literature is essential in combating antimicrobial resistance. Implementing our proposed recommendations in the Belgian ambulatory treatment guidelines could significantly enhance rational and judicious antibiotic use while minimizing the risk of 'antibiotic undertreatment. The proposed 'Choosing Wisely' recommendations have the potential to be applied to a broader (European) context.

Purpose: Obese patients treated with daptomycin at 4 mg/kg have a 30% increased drug exposure, potentially raising the risk of adverse events (AEs) like rhabdomyolysis. Given limited data on the safety of higher doses (10 mg/kg) in this population, this study aimed to assess the safety of high-dose daptomycin in obese patients and to identify potential AEs risk factors.

Methods: This multicenter, retrospective observational study was conducted from June 2021 to May 2022 using medical records. Patients with a BMI > 30 kg/m² were classified as obese. AEs assessed included: CK elevation (> 5x upper limit of normal), severe elevation (> 10x upper limit), eosinophilic pneumonia, and elevated liver enzymes. Both univariate and multivariate analyses were conducted.

Results: A total of 1 303 patients were included: 970 non-obese and 333 Ob patients. These patients received an average daptomycin dose of 9.9 mg/kg based on actual body weight for an average treatment duration of 8.27 days. One-third of the patients had CK monitoring. AEs rates were 3.5% for the n-Ob group vs. 8.7% in the Ob group (p < 0.01). Ob patients had significantly higher CK levels (n-Ob, 9.5%; Ob, 20.3%; p = 0.001), and severe elevation (n-Ob, 5.2%; Ob, 10.9%; p = 0.03). Factors increasing AE risk included obesity, concomitant prescriptions of drugs with risk of rhabdomyolysis, eGFR 30-60 mL/min, and daptomycin duration (OR = 2.42; 4.34; 2.03 and 1.05, respectively, p < 0.001). On the opposite, consultation with an infectious disease specialist reduced risk (OR = 0.52, p = 0.024).

Conclusion: This study highlights that obese patient has a significantly increased risk of AEs with high dose of daptomycin compared to non-obese patients. Adjusted body weight dosing may be considered to reduce AEs risk.

Introduction: Beta-lactam antibiotics are essential in the treatment of Gram-negative bloodstream infections. The effect of beta-lactam antibiotics depends on the time of unbound antibiotic concentration above the minimal inhibitory concentration (MIC). An antibiotic concentration above MIC during the whole dosing interval (100% ƒT > MIC) has been suggested as a target for severe infections. The aim of the present study was to compare target attainment using targets derived from known MICs with standard generic targets.

Methods: In this prospective, single-center study, adult patients with Gram-negative bloodstream infection treated with cefotaxime, piperacillin/tazobactam or meropenem were eligible for inclusion. Trough antibiotic concentrations were collected during a single dosing interval and actual MIC values for the antimicrobial agent against the infecting isolate were obtained using E-tests. Epidemiological cut off values, ECOFFs, were applied from European Committee on Antimicrobial Susceptibility Testing, EUCAST, tables for isolates within the wild-type distribution. Antibiotic concentrations were measured using Liquid Chromatography tandem Mass Spectrometry. Free concentrations were estimated based on total concentrations. Two targets based on actual MICs were assessed: free trough concentrations above (1) four times the actual MIC (100% ƒT > 4MIC) or above (2) the ECOFF (100% ƒT > ECOFF). Proportions of target attainment for the MIC-based targets were compared with attainment using clinical breakpoints or PK/PD breakpoints. Treatment response was defined as clinical resolution at day 7 (No persisting signs or symptoms of infection).

Results: We included 98 patients with a median age of 72 years. The most common microbiological finding was Escherichia coli (63%) followed by Klebsiella pneumoniae (12%). Of all patients, 77/98 patients (79%) attained 100% ƒT > 4MIC and 80/98 (82%) attained 100% ƒT > ECOFF, compared with 57/98 (58%) using 100% ƒT > EUCAST clinical breakpoints. Clinical resolution at day 7 was significantly associated with target attainment applying the target 100% ƒT > 4MIC (p = 0.013), but this was not the case when 100% ƒT > ECOFF was applied (p = 0.50).

Conclusions: In our material, higher target attainment rates were seen using targets derived from actual MICs, compared to EUCAST clinical breakpoints. Attaining 100% ƒT > 4MIC was associated with resolution of infection, but the latter finding should be interpreted cautiously.

Purpose: Genital Herpes Simplex Virus-2 (HSV-2) epidemic is highly active worldwide and can be associated with severe morbidity and mortality. This study aimed to estimate the prevalence and incidence of HSV-2 infection among a vulnerable population of active heroin injectors in Hai Phong, Vietnam, and identify associated risk factors.

Method: Associations between HSV-2 infection and socio-demographic characteristics and sexual behaviors were explored in a univariable analysis of seroprevalence. Risk factors were defined using a multivariable Poisson regression accounting for time of follow-up.

Results: HSV-2 seroprevalence at baseline was 20.8% [95%CI: 17.8-22.2] for the 1281 men people who inject drugs (PWID), and 67.4% [95%CI: 60.1-74.1] for the 184 women PWID. For HSV-2 incidence, we accumulated a follow-up time of 1156.0 and 85.9 years for men and women, respectively. Standardised incidence rate was 4 [95%CI: 2.2-7.5] and 17.5 [95%CI: 5.7-53.8] infections per 100 person-years for men and women, respectively. Factors independently associated with HSV-2 seroconversion were HIV and injecting drug use for 5-10 years for men, and declared an uncontrolled HIV viral load and the use of street methadone.

Conclusion: High HSV-2 prevalence and incidence among PWID in Hai Phong point out the burden of sexually transmissible infections in this population. Together these results advocate for a reinforcement of HSV-2 care and prevention in this population and identify PWID as future beneficiaries of upcoming therapeutic/prophylactic vaccines.

The application of cefiderocol in treating carbapenem-resistant Acinetobacter baumannii (CRAB) central nervous system (CNS) infections is rarely reported. Here we presented the case of a 66-year-old man with CRAB meningitis and purulent ventriculitis successfully treated with a combination antibiotic therapy including cefiderocol. Cerebrospinal fluid (CSF) analysis revealed normalization of glucose, chloride, protein, and lactate levels. CRAB cultures turned negative by Day 7, and metagenomics next generation sequencing (mNGS) results were negative by Day 25. The cefiderocol-contained regimen was continued for 41 days, with no recurrence of CRAB infection and no cefiderocol-associated adverse effects were observed. This case highlighted the potential of cefiderocol as a promising therapeutic option in treating CRAB CNS infections.

Purpose: Multiresistant (MR) bacteria neonatal sepsis has been progressively increasing worldwide, raising the risk of death. This study aimed to evaluate the incidence of late-onset neonatal sepsis (LOS) and the incidence of MR agents in very low birth weight (VLBW) infants in a Brazilian tertiary neonatal unit over 15 years.

Methods: This was a retrospective temporal trend study. All VLBW infants admitted from 2006 to 2020 diagnosed with LOS caused by Staphylococcus aureus, Enterococcus spp or Gram-negative bacilli were eligible.

Results: During the period, 259/1,575 (16.4%) VLBW infants had confirmed LOS, corresponding to 311 episodes of sepsis, 114 of them by agents of interest. There were 20 episodes of MR bacteria LOS (6.4% of the total confirmed LOS), corresponding to 17.5% of the cases of LOS by the studied agents, and to an incidence of 12.7/1,000 admitted VLBW infants. There was a significant trend towards a reduction in the rate of confirmed LOS (P = 0.010), while the trend of incidence of MR agents' sepsis remained stable (1.3 episodes per year - range 0-4/year). The MR incidence corresponded to 18.4% for S. aureus and 19% for Gram-negative bacilli strains. There were no cases of MR Enterococcus or carbapenemase-producing organisms. The rate of sepsis-related in-hospital death was not statistically different between the MR and non-resistant sepsis groups (15.0 versus 19.1%, P = 1,000).

Conclusion: The incidence of confirmed LOS in VLBW infants has shown a downward trend, while the rate of LOS due to MR bacteria has remained low and stable over 15 years.